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SMART@Home Feasibility Trial
Jessica King - jessica.king1@cchmc.org
ALL
12 years to 18 years old
NA
NCT06159127
Inclusion Criteria:
* Patients diagnosed with a chronic medical condition requiring regular treatment, i.e., asthma
* Ages 12-18
* English fluency for patient and caregiver
Exclusion Criteria:
* Diagnosis of pervasive developmental disorder in patient or caregiver as determined by medical chart review
* Diagnosis of serious mental illness (e.g., schizophrenia) in patient or caregiver as determined by medical chart review BEHAVIORAL: SMART@Home
Asthma, Asthma in Children
Asthma
A Study Using Nivolumab, in Combination With Chemotherapy Drugs to Treat Nasopharyngeal Carcinoma (NPC)
- cancer@cchmc.org
ALL
Up to 21 years old
PHASE2
NCT06064097
Inclusion Criteria:
* Patients must be ≤ 21 years of age at the time of study enrollment
* Newly diagnosed American Joint Committee on Cancer (AJCC) stage II-IV nasopharyngeal carcinoma (NPC)
* Patients must have had histologic verification of the malignancy at original diagnosis
* Although submission of tumor tissue for the molecular characterization initiative is not required for eligibility, it is strongly recommended
* Patients must have had histologic verification of the malignancy at original diagnosis
* Although submission of tumor tissue for the molecular characterization initiative is not required for eligibility, it is strongly recommended
* Patients must have a Lansky (for patients ≤ 16 years of age) or Karnofsky (for patients \> 16 years of age) performance status score of ≥ 60%
* Peripheral absolute neutrophil count (ANC) ≥ 1000/uL (within 7 days prior to start of protocol therapy)
* Platelet count ≥ 100,000/uL (transfusion independent) (within 7 days prior to start of protocol therapy)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 or (within 7 days prior to start of protocol therapy)
* A serum creatinine based on age/sex (within 7 days prior to start of protocol therapy) Age: Maximum serum creatinine (mg/dL)
1 month to \< 6 months: 0.4 mg/dL (male); 0.4 mg/dL (female) 6 months to \< 1 year: 0.5 mg/dL (male); 0.5 mg/dL (female)
1 to \< 2 years: 0.6 mg/dL (male); 0.6 mg/dL (female) 2 to \< 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female) 6 to \< 10 years 1 mg/dL (male); 1 mg/dL (female) 10 to \<13 years: 1.2 mg/dL (male); 1.2 mg/dL (female) 13 to \< 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
≥ 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and (within 7 days prior to start of protocol therapy)
* Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) ≤ 135 U/L\* (within 7 days prior to start of protocol therapy)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Shortening fraction of ≥ 27% by echocardiogram, or
* Ejection fraction of ≥ 50% by radionuclide angiogram
* No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months and T-cell count above the lower limit of normal are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Exclusion Criteria:
* Patients who received prior radiotherapy to the head or neck
* Patients who received prior chemotherapy or radiation for the treatment of any cancer in the last 3 years. These patients must also be in remission
* Patients with a diagnosis of immunodeficiency
* Patients with an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive agents). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Note: Patients with well-controlled asthma and no need for systemic steroids for the treatment of asthma in the last 12 months will not be excluded
* Patients with a condition requiring systemic treatment with either corticosteroids (\> 0.25 mg/kg (10 mg) daily prednisone equivalent) within 14 days or other immunosuppressive medications within 30 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 0.25 mg/kg (10 mg) daily prednisone equivalent, are permitted in the absence of active autoimmune disease
* Patients with a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
* Patients with detectable viral load of human immunodeficiency virus (HIV), hepatitis B or hepatitis C, or active tuberculosis
* Patients who have undergone solid organ or allogeneic hematopoietic transplant at any time
* Due to risks of fetal and teratogenic adverse events as seen in animal studies, a negative pregnancy test must be obtained in females of childbearing potential, defined as females who are post-menarchal. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Females of childbearing potential that are sexually active must agree to either practice 2 medically accepted highly-effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 5 months after the last dose of nivolumab, 6 months after the last dose of gemcitabine, and 14 months after the last dose of cisplatin, whichever is longer
* Males of childbearing potential that are sexually active must agree to either practice a medically accepted highly-effective methods of contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 3 months after the last dose of gemcitabine, and 11 months after the last dose of cisplatin, whichever is longer
* Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy through 5 months after the last dose of nivolumab
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Chest Radiography, DRUG: Cisplatin, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, OTHER: Electronic Health Record Review, OTHER: Fluciclovine F18, DRUG: Gemcitabine, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, BIOLOGICAL: Nivolumab, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy, PROCEDURE: X-Ray Imaging
Stage II Nasopharyngeal Carcinoma AJCC v8, Stage III Nasopharyngeal Carcinoma AJCC v8, Stage IV Nasopharyngeal Carcinoma AJCC v8
Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia (ASPEN)
Racheal Powers - Racheal.Powers@cchmc.org
ALL
2 years to 17 years old
PHASE2
NCT07441876
Inclusion Criteria:
• Participants must be aged ≥ 2 to \< 11 years (Phase 2) or ≥ 2 to \< 18 years (Phase 3), at the time of signing the informed consent
• Participants must have ACH (confirmed by documented genetic testing) and open epiphyses
• Are Tanner Stage I (Phase 2) or any Tanner stage (Phase 3)
• Are ambulatory and able to stand without assistance
Exclusion Criteria:
• Have any short stature condition other than ACH (eg, hypochondroplasia, trisomy 21, pseudoachondroplasia, GH deficiency)
• Have any of the following disorders: Hypothyroidism or hyperthyroidism, unless treated with evidence of normalized thyroid-stimulating hormone (TSH) levels, diabetes mellitus, unless considered well-controlled, autoimmune inflammatory disease, inflammatory bowel disease, autonomic neuropathy, anemia defined as hemoglobin \< 10 g/dL, vitamin D deficiency, significant hip pathology.
• Have history of any renal insufficiency or cardiac/ cardiovascular disease that places the participant at increased risk of an adverse cardiac outcome in the setting of hypotension.
• Have had bone fractures of the long bones or spine within 6 months prior to screening.
• Have used vosoritide, any other approved product (except GH, as detailed below), investigational product, or investigational medical device for the treatment of ACH or short stature at any time
• Have been treated with GH, insulin-like growth factor 1, or anabolic steroids in the 6 months prior to treatment start
DRUG: BMN 333, DRUG: Vosoritide Injection [Voxzogo]
Achondroplasia
Achondroplasia, ACH, Bone Diseases, Developmental Dwarfism, Bone Diseases, Genetic Diseases, Inborn, Musculoskeletal Diseases, Natriuretic Peptide, C-type, Osteochondrodysplasias, Physiological Effects of Drugs, Skeletal Dysplasias
Bowel Continence Across the Lifespan in People With Spina Bifida (BCALS)
Cassie Hulme - cassie.hulme@cchmc.org
ALL
5 years and over
NCT07390318
Inclusion Criteria:
* Minimum age 5 years old
* Myelomeningocele diagnosis
* Starting a retrograde or antegrade enema program (or switching from one enema program to the other)
* English or Spanish speaking/literate
Exclusion Criteria:
\- Other types of spinal dysraphism (e.g., lipomyelomeningocele, fatty filum) PROCEDURE: Retrograde Enema, PROCEDURE: Antegrade Enema
Spina Bifida, Neurogenic Bowel, Bowel Incontinence
retrograde enema, antegrade enema, bowel management program, bowel continence program, self-management, quality of life
Neuroblastoma Biology Study
- cancer@cchmc.org
ALL
31 days to 99 years old
NCT01587300
Inclusion Criteria:
* Patients must be greater than or 31 days of age.
* Patients must have had a diagnosis of high risk neuroblastoma either by histological verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
* All patients with refractory or recurrent high risk neuroblastoma at NANT institutions are eligible regardless of disease status (including no measurable or evaluable tumor) as long as they undergo a disease evaluation and appropriate samples are submitted.
* Additionally, all patients with high risk neuroblastoma without relapse treated at a NANT institution are eligible if undergoing a disease evaluation, as long as Children's Oncology Group specimens are prioritized.
Exclusion Criteria:
* There are no exclusion criteria on this study. Neuroblastoma
A Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion
- cancer@cchmc.org
ALL
Up to 21 years old
EARLY_PHASE1
NCT04655404
Inclusion Criteria:
* Age: Patients ≤ 21 years of age (birth to 21 years of age) at the time of study enrollment will be eligible.
* Diagnosis: Patients with newly-diagnosed high-grade (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors are documented in a CLIA/CAP certified lab (or clinically equivalent method considered standard in non-US sites) to harbor an NTRK fusion alteration by FISH, PCR, or next generation sequencing are eligible. Patients must have had histologically verified high-grade glioma such as anaplastic astrocytoma, glioblastoma, or H3 K27-mutant diffuse midline glioma verified at a CONNECT site.
For sites that do not have CLIA-certified equivalent (certified laboratory) to assess NTRK fusion, testing will be conducted centrally at NCH. NTRK testing will be performed by NGS using targeted RNA-sequencing (Archer Solid Tumor analysis) Please submit 10 unstained sections on charged slides at 10uM thickness, or 10 scrolls cut at 10uM thickness, along with submission of an H\&E slide. Formalin-fixed paraffin embedded (FFPE) tissue block and FFPE tissue scroll specimens must contain minimum of 25% tumor Snap-frozen tissue specimens are also acceptable and they must contain a minimum of 10% tumor. Please note that turn-around time for this test is up to 21 days.
* Disease Status: Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e. no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented NTRK fusion, must be discussed with the Study Chair on a case-by-case basis.
* Surgical Cohort ONLY: Patients with newly-diagnosed HGG with NTRK fusions who have undergone prior biopsy and for whom further resection is indicated for a more definitive surgery at an enrolling site will be eligible to enroll onto the surgical study. DIPG patients are not eligible for the surgical cohort.
* Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
* Prior Therapy: Patients must not have received any prior anti-cancer chemotherapy. Prior use of corticosteroids are allowed (see below Exclusion Criteria)
* Organ Function Requirements: Adequate Bone Marrow Function Defined as:
Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) Hemoglobin \>8 g/dL (may receive transfusions)
\- Adequate Renal Function Defined as: Serum creatinine within normal institutional limits, or Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2
\- Adequate Liver Function Defined as: Total bilirubin ≤ 2.5 × institutional upper limit of normal AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal
\- Adequate Pulmonary Function Defined as: Pulse oximetry \> 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest).
\- Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled. See Section 5.5.2 and Appendix III for EIAED guidelines.
\- Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Exclusion Criteria:
* Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
* Concomitant Medications Investigational Drugs: Patients who have previously received or are currently receiving another investigational drug are not eligible.
Anti-cancer Agents: Patients who have previously received or are currently receiving other anti-cancer agents, including chemotherapy, immunotherapy, monoclonal antibodies, biologic or targeted therapy, are not eligible
* Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.
* Patients who have received prior solid organ transplantation are not eligible.
* Patients must not have malabsorption syndrome or other condition affecting oral absorption.
* Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. (See Appendix III.) Strong inducers or inhibitors of CYP3A4 should be avoided from 7 days prior to enrollment to the end of the study.
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible. DRUG: Larotrectinib, PROCEDURE: Larotrectinib surgical
High Grade Glioma, Diffuse Intrinsic Pontine Glioma
NTRK gene fusion, BABYPOG, HIT-SKK, Larotrectinib
A Study of DB-OTO, an Adeno-Associated Virus (AAV) Based Gene Therapy, in Children/Infants, Adolescents and Adults With Hearing Loss Due to Otoferlin Mutations (CHORD)
John Greinwald, Jr. - john.greinwald@cchmc.edu
ALL
PHASE1
NCT05788536
Key
• Willingness to provide written informed consent (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) and willingness to comply with trial protocol
• Willingness to consent to genetic testing for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in order to evaluate a panel of hearing loss-related genes
• Willingness to consent to vaccinations for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in accordance with the country-specific, age-appropriate immunization schedule, as described in the protocol
• Participant able to perform all necessary assessments to qualify for enrollment and dosing in the corresponding cohort at the time the participant or parent/legal guardian signing the informed consent form (and participant providing assent, when applicable)
• Presence of biallelic, likely pathogenic or pathogenic OTOF variants
• No clinically significant laboratory findings on clinical laboratory tests at time of Screening as described in the protocol
• Audiological Criteria:
• Investigator diagnoses the participant with profound sensorineural hearing loss (SNHL; \>90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function
• Outer hair cell presence is confirmed via presence of otoacoustic emissions (≥6 dBSNR) at ≥3 frequencies from 1 to 8 kHz in the ear(s) to be infused with DB-OTO. Alternatively, for participants \>24 months of age, outer hair cell presence can be confirmed via presence of the cochlear microphonic in the ear(s) to be infused with DB-OTO.
• No evidence from measures of hearing loss that show a dependence on body temperature
• From study start and for the duration of the short-term follow-up period (48 weeks): Female participants of childbearing potential and fertile males, must agree to use highly effective contraception. Female participants must agree not to become pregnant. Fertile male participants must agree not to father a child or donate sperm, for 48 weeks and in cases of early withdrawal, for at least 12 months after DB-OTO administration. Key
• History of prior treatment with gene therapy
• Surgical anatomy that would preclude or meaningfully impact the planned surgical approach as indicated by medical imaging (eg, Computed Tomography \[CT\] or Magnetic Resonance Imaging \[MRI\]) in the ear(s) to be infused with DB-OTO
• History or presence of other permanent or untreatable hearing loss conditions
• Prior or current history of malignancies
• Prior or current history of meningitis
• History or presence of cochlear implants in the ear(s) to be infused with DB-OTO
• History of risk factor(s) for auditory neuropathy not caused by OTOF pathogenic variants including but not limited to: prematurity, low birth weight, hyperbilirubinemia, Neonatal Intensive Care Unit (NICU) admission, and/or low Apgar scores as described in the protocol Note: Other protocol-defined inclusion/exclusion criteria apply
Inclusion Criteria:
• Willingness to provide written informed consent (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) and willingness to comply with trial protocol
• Willingness to consent to genetic testing for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in order to evaluate a panel of hearing loss-related genes
• Willingness to consent to vaccinations for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in accordance with the country-specific, age-appropriate immunization schedule, as described in the protocol
• Participant able to perform all necessary assessments to qualify for enrollment and dosing in the corresponding cohort at the time the participant or parent/legal guardian signing the informed consent form (and participant providing assent, when applicable)
• Presence of biallelic, likely pathogenic or pathogenic OTOF variants
• No clinically significant laboratory findings on clinical laboratory tests at time of Screening as described in the protocol
• Audiological Criteria:
• Investigator diagnoses the participant with profound sensorineural hearing loss (SNHL; \>90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function
• Outer hair cell presence is confirmed via presence of otoacoustic emissions (≥6 dBSNR) at ≥3 frequencies from 1 to 8 kHz in the ear(s) to be infused with DB-OTO. Alternatively, for participants \>24 months of age, outer hair cell presence can be confirmed via presence of the cochlear microphonic in the ear(s) to be infused with DB-OTO.
• No evidence from measures of hearing loss that show a dependence on body temperature
• From study start and for the duration of the short-term follow-up period (48 weeks): Female participants of childbearing potential and fertile males, must agree to use highly effective contraception. Female participants must agree not to become pregnant. Fertile male participants must agree not to father a child or donate sperm, for 48 weeks and in cases of early withdrawal, for at least 12 months after DB-OTO administration. Key
Exclusion Criteria:
• History of prior treatment with gene therapy
• Surgical anatomy that would preclude or meaningfully impact the planned surgical approach as indicated by medical imaging (eg, Computed Tomography \[CT\] or Magnetic Resonance Imaging \[MRI\]) in the ear(s) to be infused with DB-OTO
• History or presence of other permanent or untreatable hearing loss conditions
• Prior or current history of malignancies
• Prior or current history of meningitis
• History or presence of cochlear implants in the ear(s) to be infused with DB-OTO
• History of risk factor(s) for auditory neuropathy not caused by OTOF pathogenic variants including but not limited to: prematurity, low birth weight, hyperbilirubinemia, Neonatal Intensive Care Unit (NICU) admission, and/or low Apgar scores as described in the protocol Note: Other protocol-defined inclusion/exclusion criteria apply
GENETIC: DB-OTO
Congenital Hearing Loss Secondary to Biallelic Mutations of the Otoferlin Gene (OTOF)
DB-OTO, Gene Therapy, Congenital Hearing Loss, Sensorineural Hearing Loss, Auditory Neuropathy, Pediatric, Cochlear Implant, Otoferlin, Deaf, Hard of hearing, Hearing impaired, Hearing disorder, Fully implantable hearing aid, Child, Infant, Adolescents, Young Adults, Adults, CHORD
Phase 2b Study of RPT904 as Monotherapy in Participants With IgE-Mediated Food Allergy
Constance Harpring - constance.harpring@cchmc.org
ALL
12 years to 55 years old
PHASE2
NCT07220811
Key
Inclusion Criteria:
* Participant and/or parent/legal guardian must be able to understand and provide informed consent and/or assent, as applicable.
* Male or female, 12 to less than 56 years of age at screening.
* Allergic to at least 1 of the following foods: peanut, milk, egg, cashew, or walnut, as confirmed by the following criteria:
* a. For participants aged 12 to \<18 years:
* i. Allergic to peanut: participant must meet all criteria below:
* 1\. Positive SPT (≥4 mm wheal greater than saline control) to peanut.
* 2\. Positive peanut IgE (≥6 kUA/L) at screening or within 3 months of screening.
* 3\. Positive blinded oral food challenge (OFC) to peanut during the screening DBPCFC, defined as experiencing dose-limiting symptoms at a single dose of ≤100 mg (ie, cumulative dose of ≤144 mg) of peanut protein.
* ii. Allergic to milk or egg: unable to tolerate both cooked and uncooked forms:
* 1\. Positive SPT (≥4 mm wheal greater than saline control) to the specific food.
* 2\. Positive food-specific IgE (≥6 kUA/L) at screening or within 3 months of screening.
* 3\. Positive blinded OFC to the specific food during the screening DBPCFC, defined as experiencing dose-limiting symptoms at a single dose of ≤300 mg (ie, cumulative dose of ≤444 mg) of food protein.
* iii. Allergic to cashew: participant must meet all criteria below:
* 1\. Positive SPT (≥4 mm wheal greater than saline control) to cashew. OR
* 2\. Positive cashew IgE (≥6 kUA/L) at screening or within 3 months of screening. AND
* 3\. Positive blinded OFC to cashew during the screening DBPCFC, defined as experiencing dose-limiting symptoms at a single dose of ≤100 mg (ie, cumulative dose of ≤144 mg) of cashew protein.
* iv. Allergic to walnut: participant must meet all criteria below:
* 1\. Positive SPT (≥4 mm wheal greater than saline control) to walnut. OR
* 2\. Positive walnut IgE (≥6 kUA/L) at screening or within 3 months of screening AND
* 3\. Positive blinded OFC to walnut during the screening DBPCFC, defined as experiencing dose-limiting symptoms at a single dose of ≤300 mg (ie, cumulative dose of ≤444 mg) of walnut protein.
* b. For participants aged 18 to \<56 years:
* i. Allergic to peanut or cashew: participant must meet all of the following criteria:
* 1\. Positive SPT (≥3 mm wheal greater than saline control) to peanut or cashew.
* 2\. Positive peanut or cashew IgE (≥0.35 kUA/L) at screening or within 3 months of screening.
* 3\. Positive blinded OFC to peanut or cashew during the screening DBPCFC, defined as experiencing dose-limiting symptoms at a single dose of ≤100 mg (ie, cumulative dose of ≤144 mg) of peanut or cashew protein.
* ii. Allergic to milk or egg: participant must meet all of the following criteria:
* 1\. Positive SPT (≥3 mm wheal greater than saline control) to the specific food.
* 2\. Positive food-specific IgE (≥0.35 kUA/L) at screening or within 3 months of screening.
* 3\. Positive blinded OFC to the specific food during the screening DBPCFC, defined as experiencing dose-limiting symptoms at a single dose of ≤300 mg (ie, cumulative dose of ≤444 mg) of food protein.
* iii. Allergic to walnut: participant must meet all of the following criteria:
* 1\. Positive SPT (≥3 mm wheal greater than saline control) to walnut.
* 2\. Positive walnut IgE (≥0.35 kUA/L) at screening or within 3 months of screening.
* 3\. Positive blinded OFC to walnut during the screening DBPCFC, defined as experiencing dose-limiting symptoms at a single dose of ≤300 mg (ie cumulative dose of ≤444 mg) of walnut protein.
* With body weight (as measured at screening) and total serum IgE level (as measured within 3 months of screening) suitable for RPT904 dosing (per RPT904 dosing table).
* Female Participants:
* 1\. Must not be pregnant or breastfeeding.
* 2\. Women of non-childbearing potential (e.g., surgically sterile or postmenopausal) are eligible.
* 3\. Women of childbearing potential must have a negative pregnancy test before starting study treatment, agree to use a protocol-defined method of contraception during the study and for at least 16 months after the last dose, and must not donate eggs or undergo egg retrieval during this period.
* Male Participants:
* 1\. Must agree to either remain abstinent from heterosexual intercourse (if that is their usual lifestyle) or use protocol-defined contraception during the study and for 16 months after the last dose.
* 2\. Must not donate semen or participate in sperm banking during this time, and if they have a female partner of childbearing potential, she should also use effective contraception.
Exclusion Criteria:
* Clinically significant lab abnormalities at screening.
* Sensitivity or suspected/known allergy to any component of the active or placebo OFC material (excluding the test allergens peanut, milk, egg, walnut, and cashew being tested), or drugs related to RPT904 (eg, monoclonal antibodies, polyclonal gamma globulin).
* Uncontrolled or severe asthma/wheezing at screening.
* Current use of oral, IM, or IV corticosteroids, tricyclic antidepressants, or β-blockers (oral or topical).
* Past or current immunotherapy to any study foods within 6 months of screening.
* Treatment with immunomodulatory therapy within 6 months of screening.
* Currently in the "build-up phase" of inhalant allergen immunotherapy (i.e., not yet on maintenance). Note: individuals on stable maintenance dosing may be eligible.
* Past or current medical problems (eg, severe latex allergy), chronic diseases (other than asthma/wheezing, atopic dermatitis, or rhinitis) requiring therapy (eg, heart disease, diabetes), abnormal physical findings or lab results not listed above that, in the Principal Investigator's opinion, may increase study related risks, hinder protocol compliance, or impact data quality or interpretation . DRUG: RPT904, DRUG: RPT904, OTHER: Placebo, DRUG: RPT904, DRUG: RPT904, OTHER: Placebo
Ig-E Mediated Food Allergy
Ig-E Mediated food allergy, peanut allergy, milk allergy, egg allergy, cashew allergy, walnut allergy, RPT904, placebo, double-blind placebo-controlled food challenge (DBPCFC), ozureprubart, JYB1904
REVEAL: A Phase 3 Study of Obudanersen (ION582) in Angelman Syndrome
Mary Cabrera-Thurman - Mary.Cabrera-Thurman@cchmc.org
ALL
2 years to 50 years old
PHASE3
NCT06914609
Key
• The participants caregiver(s)/ legally authorized representative must have given written informed consent and any authorizations required by local law and be able to comply with all study requirements.
• Medically stable and can undergo sedation and/or general anesthesia without intubation.
• Male or female between 2 and lesser than or equal to (≤)50 years of age, depending on specific cohort, at the time of the in-clinic Screening visit.
• Participant has a clinical diagnosis of Angelman syndrome (AS) with molecular confirmation of either Ubiquitin-protein ligase E3A (UBE3A) deletion or UBE3A mutation.
• Currently receiving stable doses of concomitant medications typically prescribed for AS, such as anti-epileptic medication, behavioral management medications, sleep medications, gabapentin, cannabidiol, and special diets, supplements, or nutritional support for at least 8 weeks prior to the Baseline visit.
• Legally authorized representative/caregiver(s) agree(s) not to post any of the participant's personal medical data or information related to the study on any website or social media site (e.g., Facebook, Instagram, X (formerly Twitter), YouTube, TikTok, etc.) from the time of enrollment until they are notified that the study is completed. Key
• Must not have any clinically significant abnormalities in medical history (e.g., major surgery within 3 months of screening), or on physical examination for which treatment with an antisense oligonucleotide (ASO) would be contraindicated or which, in the opinion of the Principal Investigator (PI), could confound the results of this study.
• Known brain or spinal disease that would interfere with the lumbar puncture (LP) procedure, cerebrospinal fluid (CSF) circulation, or presence of other factors would affect the safety of the LP procedure.
• Must not have any other conditions, which, in the opinion of the Investigator, would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study.
• Must not have any laboratory abnormalities or any other clinically significant abnormalities that would, as assessed by the Investigator, at screening or Baseline, render a participant unsuitable for inclusion.
• Previous treatment with an oligonucleotide (including small interfering ribonucleic acid (RNA) \[siRNA\], ASOs) gene therapy or gene editing. This exclusion criterion does not apply to approved nucleic acid-based vaccines, including mRNA vaccines, which are allowed.
• Has molecular confirmation of AS due to paternal uniparental disomy, imprinting center defect, or mosaic findings. Other inclusion/exclusion criteria may apply.
Inclusion Criteria:
• The participants caregiver(s)/ legally authorized representative must have given written informed consent and any authorizations required by local law and be able to comply with all study requirements.
• Medically stable and can undergo sedation and/or general anesthesia without intubation.
• Male or female between 2 and lesser than or equal to (≤)50 years of age, depending on specific cohort, at the time of the in-clinic Screening visit.
• Participant has a clinical diagnosis of Angelman syndrome (AS) with molecular confirmation of either Ubiquitin-protein ligase E3A (UBE3A) deletion or UBE3A mutation.
• Currently receiving stable doses of concomitant medications typically prescribed for AS, such as anti-epileptic medication, behavioral management medications, sleep medications, gabapentin, cannabidiol, and special diets, supplements, or nutritional support for at least 8 weeks prior to the Baseline visit.
• Legally authorized representative/caregiver(s) agree(s) not to post any of the participant's personal medical data or information related to the study on any website or social media site (e.g., Facebook, Instagram, X (formerly Twitter), YouTube, TikTok, etc.) from the time of enrollment until they are notified that the study is completed. Key
Exclusion Criteria:
• Must not have any clinically significant abnormalities in medical history (e.g., major surgery within 3 months of screening), or on physical examination for which treatment with an antisense oligonucleotide (ASO) would be contraindicated or which, in the opinion of the Principal Investigator (PI), could confound the results of this study.
• Known brain or spinal disease that would interfere with the lumbar puncture (LP) procedure, cerebrospinal fluid (CSF) circulation, or presence of other factors would affect the safety of the LP procedure.
• Must not have any other conditions, which, in the opinion of the Investigator, would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study.
• Must not have any laboratory abnormalities or any other clinically significant abnormalities that would, as assessed by the Investigator, at screening or Baseline, render a participant unsuitable for inclusion.
• Previous treatment with an oligonucleotide (including small interfering ribonucleic acid (RNA) \[siRNA\], ASOs) gene therapy or gene editing. This exclusion criterion does not apply to approved nucleic acid-based vaccines, including mRNA vaccines, which are allowed.
• Has molecular confirmation of AS due to paternal uniparental disomy, imprinting center defect, or mosaic findings. Other inclusion/exclusion criteria may apply.
DRUG: obudanersen, DRUG: Placebo
Angelman Syndrome
ION582, Angelman Syndrome
ES Catheter vs Cryoablation After Pectus Surgery
Kristie Geisler - kristie.geisler@cchmc.org
ALL
12 years to 21 years old
NA
NCT06682208
Inclusion Criteria:
* Age 12 - 21 years
* History of pectus excavatum
* Scheduled for Nuss procedure
Exclusion Criteria:
* Prior pectus repair
* Other concomitant surgeries
* Chronic pain conditions including Ehlers Danlos Syndrome
* Non-English speaking - rationale: the questionnaires used in the study are in English language and the social and cultural factors of pain perception of non-English speaking patients could affect the study power
* Severe developmental delays including cognitive (difficulties understanding), motor (cerebral palsy or muscular dystrophy), and speech delays (difficulties communicating)
* History of or active renal or liver disease
* Major surgery requiring opioids in the last 2 years
* Severe respiratory problems (such as obstructive sleep apnea, cystic fibrosis, pulmonary fibrosis, or pneumonia within the last month)
* Cardiac conditions including, but not limited to, cyanotic heart disease, hypoplastic left ventricle, arrhythmia, uncontrolled hypertension with ongoing treatment, Kawasaki disease, or cardiomyopathies. Participants with asymptomatic valvular lesions or defects may be included
* BMI \>35
* Pregnant or breastfeeding females PROCEDURE: ES catheter, PROCEDURE: Intercostal nerve cryoablation (INC)
Pectus Excavatum
Natural History of Cerebral Palsy Prospective Study
Karen L Harpster, PhD, OTR/L - karen.harpster@cchmc.org
ALL
3 months to 24 months old
NCT05576948
Inclusion Criteria:
* Infants will be included if they have a diagnosis of CP or "at high risk of CP" and under the age of 12 months.
* Infants at high risk of CP as defined by any two (any combination) of the following:
• Neuroimaging predictive of a motor disability including the involvement of 1 or more of the following structures: sensori-motor cortex, Basal Ganglia, Posterior Limb of the Internal Capsule, pyramids.
• Trajectory of cramped synchronized general movements (GMs) on General Movement Assessment (GMA) OR absent fidgety GMs at fidgety age
• Hammersmith Infant Neurological Exam (HINE) scores \<57 @ 3months or \<60 @ 6months or \<63 @9 months Infants will also be included if they meet BOTH of the following criteria (even if infants have a HINE score greater than the cut off scores stated above: i. Unilateral brain injury on neuroimaging (magnetic resonance imaging (MRI) or cranial ultrasound (CUS)) predictive of CP ii. Clinical signs of asymmetry
Exclusion Criteria:
* Infants with progressive or neurodegenerative disorders or genetic disorders not associated with CP
* Infants with other disability diagnoses e.g. Down Syndrome Cerebral Palsy
OMEGA: Outcome Measures in Eosinophilic Gastrointestinal Disorders Across the Ages (OMEGA)
Bliss Magella - bliss.magella@cchmc.org
ALL
3 years and over
NCT02523118
Inclusion Criteria:
* Males or females 3 years of age and older
* Mucosal eosinophilia:
EoE ≥ 15 eosinophils/HPF in the distal or proximal esophagus EoG ≥ 30 eosinophils/HPF in 5 HPF\'s in the body and/or antrum EoN ≥ 53 eosinophils/HPF in the duodenum and/or ≥ 56 eosinophils/HPF in the jejunum and/or ileum EoC ≥ 84 eosinophils/HPF from the transverse or descending colon and/or ≥ 32 eosinophils/HPF from the rectosigmoid colon or a biopsy from any colonic location with ≥ 100 eosinophils/HPF
\- Presence of symptoms is required for patients who are newly diagnosed but not required for patients who were previously diagnosed.
Exclusion Criteria:
* History of intestinal surgery other than G tube placement
* Enrolled in a blinded investigational study at the time of the first study visit
* Have esophageal stricture (\<3mm)
* Have other identifiable causes for eosinophilia (except Inflammatory Bowel Disease): infections, Gastrointestinal (GI) cancer, other GI inflammatory disease (e.g., Ulcerative Colitis or Crohn\'s Disease) Eosinophilic Gastrointestinal Disorders (EGIDs), Eosinophilic Esophagitis, Eosinophilic Gastritis, Eosinophilic Gastroenteritis, Eosinophilic Colitis
The BRIDGE Pain Study (BRIDGE)
Megan Kirschman - bridgestudy@cchmc.org
ALL
14 years to 26 years old
NCT07602595
Inclusion Criteria:
* Diagnosis of rheumatic/autoimmune disease/pain condition or surgery prior to age 18; Current age 14 to 26 years; Participant (and parent/legal guardian of participants \< 18 yo) can read and write in English; At least 1 year from diagnosis of pain or rheumatic disease; For individuals with MSK surgical history, at least 1 year after initial surgical intervention; For individuals with rheumatic disease, their disease must be considered inactive
Exclusion Criteria:
* They have active disease, or Other major medical comorbidities have developed after surgery following MSK surgical intervention. OTHER: Not applicable- observational study
Juvenile Idiopathic Arthritis (JIA), Fibromyalgia, Lupus, Scoliosis, Pectus Excavatum, Chronic Pain, Musculoskeletal Pain
Study of MRM-3379 in Male Participants With Fragile X Syndrome (BLOOM)
Hannah Sachs - Hannah.Sachs@cchmc.org
MALE
13 years to 45 years old
PHASE2
NCT07209462
Inclusion Criteria:
* Willing and able to provide signed informed consent/assent. Where local regulations permit inclusion of participants deemed unable to provide informed consent, a legally authorized representative must provide informed consent on the participant's behalf, and the participant must provide assent if applicable.
* Male, 13-45 years of age (inclusive)
* Weight ≥30 kg and BMI between 18 and 36 kg/m2 (inclusive) at the screening visit
* Diagnosis of FXS with a molecular genetic ≥200 CGG repetitions .
* Able to perform the PVT and ORRT of the NIH-TCB
* Have a consistent caregiver(s) who is willing and able to be present regularly and reliably with the participant
* Able to swallow tablets or capsules
Exclusion Criteria:
History of or current medical condition other than FXS and related issues that would place the participant at higher risk from study participation DRUG: Low dose of MRM-3379, DRUG: Middle Dose of MRM-3379, DRUG: High dose of MRM-3379, DRUG: Placebo, DRUG: Low dose of MRM-3379 Open-Label
Fragile X Syndrome
Fragile X Syndrome, FXS, FMR, Phosphodiesterase 4, PDE4
Global Patient Registry to Monitor Long-term Safety and Effectiveness of Increlex® in Children and Adolescents With Severe Primary Insulin-like Growth Factor-1 Deficiency (SPIGFD).
Leah Tyzinski - Leah.Tyzinski@cchmc.org
ALL
2 years to 18 years old
NCT00903110
Inclusion Criteria:
* For US : patients starting or planning to start or currently receiving treatment with Increlex® therapy for severe primary IGF-1 deficiency as defined by the US Increlex® prescribing information or for growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.For EU : patients starting or planning to start or currently receiving treatment with Increlex® therapy according to the locally approved product information.
* Parents or legally authorized representatives if applicable must give signed informed consent before any registry-related activities are conducted. Assent from the subject should also be obtained as appropriate
Exclusion Criteria:
* Subject currently participating in an Increlex® clinical trial
* Subject currently participating in any clinical trial for growth retardation
* Patient with any contraindication to Increlex® or any condition subject to special warning as per the locally approved label
* For US patients, these include patients with hypersensitivity to the active substance or any of the excipients, patients with active or suspected neoplasia and patients with closed epiphyses.
* For EU patients: these include patients with hypersensitivity to the active substance or any of the excipients, patients with active or suspected neoplasia or any condition or medical history which increases the risk of benign or malignant neoplasia and patients with closed epiphyses DRUG: Increlex®
IGF1 Deficiency
Prevention of Graft Rejection in Hematopoietic Stem Cell Transplant (HSCT) Recipients
Jessica Anderson - jessica.anderson@cchmc.org
ALL
EARLY_PHASE1
NCT07244419
Inclusion Criteria:
* All patients undergoing allogeneic HSCT at our institution will be evaluated for graft rejection risk factors. Patients deemed high risk for graft rejection will have 2 or more of the following: mismatched or haploidentical donor, ex vivo t-cell depleted graft, prior history of graft rejection.
Exclusion Criteria:
* Known hypersensitivity to any constituent of the study medication. DRUG: Emapalumab 3 mg/kg, DRUG: Emapalumab 10 mg/kg
Hematopoietic Stem Cell Transplantation, Graft Failure
Zoledronate to Prevent Bone Health Complications in Pediatric Hematopoietic Stem Cell Transplant Survivors
Jessica Anderson - jessica.anderson@cchmc.org
ALL
5 years to 18 years old
PHASE1
NCT07375290
Inclusion Criteria:
* Patients ≥5 and ≤18 years old who are preparing for HSCT with a height-for-age corrected DXA Z-score of \<-2.0 and admitted to a CCHMC inpatient unit.
* Patients ≥5 and ≤18 years old recovering from HSCT and who have developed de novo acute or chronic GVHD and are admitted to a CCHMC inpatient unit.
Exclusion Criteria:
* Age \<5 years and \>18 years
* Patients with Fanconi anemia or other radiation-sensitive syndromes with increased malignancy risk
* history of prior bisphosphonate use
* low 25-OH vitamin D levels (\<20 ng/mL)
* active febrile illness
* uncontrolled infection
* Elevated creatinine at the time of enrollment, history or renal failure, or documented low glomerular filtration rate (GFR≤90)
* Active bone disease including history of abnormal PTH level for any reason, active bone fracture/healing, or primary disorder of bone development or metabolism.
* Women who are pregnant or breast feeding. DRUG: Zoledronate
Hematopoietic Stem Cell Transplantation
A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation (The ReInspire Study)
Sarah Price - Sarah.price@cchmc.org
ALL
2 years and over
PHASE2
NCT06789913
Key
• Systemic therapy or antibody within 5 half-lives of the therapy.
• Local therapy including radiation, surgery, or other procedures within 28 days; lesion(s) must have demonstrated progression after the procedure.
Inclusion Criteria:
* The participant must have a clinical diagnosis of PROS or a malformation within the ISSVA classification.
* One or more documented activating PIK3CA mutation(s) that are targeted by selective PI3Kα inhibitors in lesional tissue and/or cell-free DNA from the lesion or blood. Some participants may be eligible without a documented PIK3CA mutation, with the sponsor's approval, as long as no other genetic driver has been documented.
* Lansky (\<16 yo) or Karnofsky (≥16 yo) performance status of ≥50.
* Agree to provide archived lesional fluid and/or tissue or be willing to undergo pretreatment lesional biopsy (if considered safe and medically feasible) to assess PIK3CA status.
Key Exclusion Criteria:
* Known hypersensitivity to RLY-2608.
* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
* Clinically significant, uncontrolled cardiovascular disease
* Received disease-directed therapy prior to the first dose of study drug:
• Systemic therapy or antibody within 5 half-lives of the therapy.
• Local therapy including radiation, surgery, or other procedures within 28 days; lesion(s) must have demonstrated progression after the procedure.
DRUG: RLY-2608, DRUG: Placebo
PIK3CA-Related Overgrowth Spectrum (PROS), Lymphatic Malformations, Vascular Malformations, PIK3CA Mutation, CLOVES Syndrome, Klippel Trenaunay Syndrome, Megalencephaly-capillary Malformation Polymicrogyria Syndrome (MCAP), Vascular Anomalies
Target Trial Emulation for Pharmacologic Treatment of Neonatal Opioid Withdrawal Syndrome (TreaT NOW)
Traci Beiersdorfer - Traci.Beiersdorfer@cchmc.org
ALL
Not specified
NCT07278375
Inclusion Criteria:
• Infant is ≥ 36 weeks' gestational age
• Infant had antenatal opioid exposure identified by at least one of the following:
• History of maternal opioid use during the second and/or third trimester of pregnancy as noted in the mother's or infant's medical record;
• Positive maternal toxicology screen for opioids during the second or third trimester of pregnancy; and/or
• Positive infant toxicology screen for opioids during the initial hospital stay.
• The infant is being assessed and managed for NOWS at an eligible study site.
• The infant is at risk for pharmacologic treatment for NOWS defined by either of the following: * At least 1 score ≥ 8 if assessed and managed with the Finnegan Neonatal Abstinence Scoring Tool (FNAST) or modification thereof * At least 1 "yes" if assessed and managed with the Eat, Sleep, Console (ESC) care approach
• Infant met all inclusion criteria on or after March 25, 2024.
Exclusion Criteria:
• Infant has major congenital anomalies.
• Infant has neonatal encephalopathy (inclusive of hypoxic ischemic encephalopathy), a metabolic disorder, stroke, intracranial hemorrhage, or meningitis diagnosed prior to the initiation of pharmacologic treatment.
• Infant is receiving respiratory support (any positive pressure or oxygen therapy) at 48 hours of age.
• Infant has undergone major surgical intervention prior to or at 48 hours of age.
• Infant has postnatal opioid exposure prior to the initiation of pharmacologic treatment for NOWS.
• Infant was outborn and pharmacologic treatment was initiated at the transferring hospital.
Neonatal Opioid Withdrawal Syndrome
Neonatal Opioid Withdrawal Syndrome, NOWS
Zinc Supplementation in Sickle Cell Disease: A Precursor to the Think Zinc for Bones Trial (ZnSCD)
Amy Shova - Amy.Shova@cchmc.org
ALL
15 years to 40 years old
PHASE2
NCT06260891
Inclusion Criteria:
* Age: ≥ 15.0 to ≤ 40.0 years
* Diagnosis: SCD-SS or SCD-S Beta zero Thalassemia, in steady state (defined as a minimum of 2 weeks days following pain crisis)
* Male or Female
Exclusion Criteria:
* Taking any supplement containing zinc and unable/willing to stop for 3 months prior to study start
* 25-Hydroxy Vitamin D \< 20 ng/mL
* On chronic transfusion therapy (defined as \>8 Transfusions/year) and iron overloaded (defined as liver iron concentration \> 7 mg/g OR average serum ferritin \>4000 ug/L)
* Unable swallow pills or take daily supplement as instructed
* Currently participating in another investigational drug trial
* Prior diagnosis of chronic kidney disease (eGFR \< 30 mL/min/1.73m2) DRUG: 25 mg/day zinc, DRUG: 40 mg/day zinc
Sickle Cell Disease
A Study of Mavorixafor in Participants With Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent and/or Serious Infections
Joan Moore - Joan.Moore@cchmc.org
ALL
12 years and over
PHASE3
NCT06056297
Key
• Isolated with a permanent (non-cyclic) presentation, for example, elastase, neutrophil expressed (ELANE), colony stimulating factor 3 receptor (CSF3R), C-X-C chemokine receptor 2 (CXCR2), Wiskott-Aldrich syndrome (WAS)
• Associated with extra-hematologic manifestations, for example, Barth syndrome, Cohen syndrome, glucose-6-phosphatase catalytic subunit 3 (G6PC3), Kostmann disease
• Associated with metabolic disorders, for example, glycogen storage disease 1b (GSD1b)
• Shwachman-Diamond syndrome * Acquired Primary Neutropenia
• Chronic idiopathic neutropenia
• Primary autoimmune neutropenia. Other chronic neutropenia (CN) disorders that may be eligible for enrollment can be clarified and approved upon discussion with study Medical Monitor. * Have an ANC \<1000 cells/µL during screening (single ANC value from hematology) and confirmed trough mean ANC (mean value of multiple ANC measurements over 6 hours) at baseline visit, with no clinical evidence of systemic infection. * Prior history of recurrent and/or serious infections during the 12 months preceding the screening visit (that is, suffering sequelae of chronic neutropenia), as defined by having at least 2 infections in the last 12 months that meet the following criteria: * Infection requiring the use of antibiotics (intravenous \[IV\]/oral); OR * Infection requiring a visit to healthcare facility (including but not limited to emergency room visit, urgent care facility, primary care physician's office, or in-patient hospitalization); AND for all potential participants: * Infections considered by the Investigator to be likely related to the potential participant's CN disorder. * Participants who are on G-CSF or other active background therapy must have been receiving these therapies during the previous 12 months while continuing to suffer from infections, be on a stable dose and dosing schedule for ≥4 weeks prior to screening visit and remain on this dose and dosing schedule throughout the study (unless ANC \>10,000 cells/µL for ≥4 weeks). * Participants must be willing to keep their G-CSF or other background therapy doses/regimens stable (other than for safety reasons) for the duration of the study. Key
• Hypersplenism
• Infection
• Malignancy
• Autoimmune disease, for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, graft-versus-host disease, thyroid disease
• Nutritional deficiency, for example, vitamin B12, folic acid, copper, caloric malnutrition
• Drug-induced cause, for example, chemotherapy, clozapine, antiretrovirals, antibiotics, monoclonal antibodies. * A diagnosis of any of the following:
• Aplastic anemia
• Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome
• Certain CNs, including but not limited to these classifications are excluded:
• Isolated with a cyclic presentation, for example, elastase, neutrophil expressed (ELANE)
• Associated with immune dysregulation, for example, common variable immunodeficiency (CVID), autoimmune lymphoproliferative syndrome (ALPS), familial hemophagocytic lymphohistiocytosis, Chédiak-Higashi syndrome, GATA-binding protein 2 (GATA2) deficiency syndrome
• Associated with bone marrow failure, for example, Fanconi anemia, Diamond-Blackfan anemia
• Neutropenia associated with a Duffy-null phenotype (formerly known as benign ethnic neutropenia). However, a participant with an autosomal dominant pathogenic variant in a gene associated with CN on a Duffy-null background may be eligible for inclusion * A medical or personal condition that may potentially compromise the safety of the participant, may preclude the participant's successful completion of the clinical study, or could, in the opinion of the Investigator or the Medical Monitor, interfere with the objectives of the study. * Received more than 1 dose of mavorixafor in the past. * Received C-X-C chemokine receptor 4 (CXCR4) antagonist (other than mavorixafor) in the past 6 months. * Participants taking pegylated-G-CSF unless they have a diagnosis of congenital neutropenia confirmed at screening. * Participant is currently taking or has taken other investigational drug \<30 days prior to the screening visit or 5 half-lives, whichever is longer. Note: Other protocol-defined inclusion and exclusion criteria may apply.
Inclusion Criteria:
* Diagnosis of congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorder ≥6 months prior to the screening visit that is not attributable to medications, active or recent infections or malignancy.
* Congenital Neutropenia, including but not limited to these classifications:
• Isolated with a permanent (non-cyclic) presentation, for example, elastase, neutrophil expressed (ELANE), colony stimulating factor 3 receptor (CSF3R), C-X-C chemokine receptor 2 (CXCR2), Wiskott-Aldrich syndrome (WAS)
• Associated with extra-hematologic manifestations, for example, Barth syndrome, Cohen syndrome, glucose-6-phosphatase catalytic subunit 3 (G6PC3), Kostmann disease
• Associated with metabolic disorders, for example, glycogen storage disease 1b (GSD1b)
• Shwachman-Diamond syndrome * Acquired Primary Neutropenia
• Chronic idiopathic neutropenia
• Primary autoimmune neutropenia. Other chronic neutropenia (CN) disorders that may be eligible for enrollment can be clarified and approved upon discussion with study Medical Monitor. * Have an ANC \<1000 cells/µL during screening (single ANC value from hematology) and confirmed trough mean ANC (mean value of multiple ANC measurements over 6 hours) at baseline visit, with no clinical evidence of systemic infection. * Prior history of recurrent and/or serious infections during the 12 months preceding the screening visit (that is, suffering sequelae of chronic neutropenia), as defined by having at least 2 infections in the last 12 months that meet the following criteria: * Infection requiring the use of antibiotics (intravenous \[IV\]/oral); OR * Infection requiring a visit to healthcare facility (including but not limited to emergency room visit, urgent care facility, primary care physician's office, or in-patient hospitalization); AND for all potential participants: * Infections considered by the Investigator to be likely related to the potential participant's CN disorder. * Participants who are on G-CSF or other active background therapy must have been receiving these therapies during the previous 12 months while continuing to suffer from infections, be on a stable dose and dosing schedule for ≥4 weeks prior to screening visit and remain on this dose and dosing schedule throughout the study (unless ANC \>10,000 cells/µL for ≥4 weeks). * Participants must be willing to keep their G-CSF or other background therapy doses/regimens stable (other than for safety reasons) for the duration of the study. Key
Exclusion Criteria:
* A diagnosis of secondary neutropenia including those due to:
• Hypersplenism
• Infection
• Malignancy
• Autoimmune disease, for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, graft-versus-host disease, thyroid disease
• Nutritional deficiency, for example, vitamin B12, folic acid, copper, caloric malnutrition
• Drug-induced cause, for example, chemotherapy, clozapine, antiretrovirals, antibiotics, monoclonal antibodies. * A diagnosis of any of the following:
• Aplastic anemia
• Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome
• Certain CNs, including but not limited to these classifications are excluded:
• Isolated with a cyclic presentation, for example, elastase, neutrophil expressed (ELANE)
• Associated with immune dysregulation, for example, common variable immunodeficiency (CVID), autoimmune lymphoproliferative syndrome (ALPS), familial hemophagocytic lymphohistiocytosis, Chédiak-Higashi syndrome, GATA-binding protein 2 (GATA2) deficiency syndrome
• Associated with bone marrow failure, for example, Fanconi anemia, Diamond-Blackfan anemia
• Neutropenia associated with a Duffy-null phenotype (formerly known as benign ethnic neutropenia). However, a participant with an autosomal dominant pathogenic variant in a gene associated with CN on a Duffy-null background may be eligible for inclusion * A medical or personal condition that may potentially compromise the safety of the participant, may preclude the participant's successful completion of the clinical study, or could, in the opinion of the Investigator or the Medical Monitor, interfere with the objectives of the study. * Received more than 1 dose of mavorixafor in the past. * Received C-X-C chemokine receptor 4 (CXCR4) antagonist (other than mavorixafor) in the past 6 months. * Participants taking pegylated-G-CSF unless they have a diagnosis of congenital neutropenia confirmed at screening. * Participant is currently taking or has taken other investigational drug \<30 days prior to the screening visit or 5 half-lives, whichever is longer. Note: Other protocol-defined inclusion and exclusion criteria may apply.
DRUG: Mavorixafor, DRUG: Placebo
Neutropenia
Mavorixafor, Chronic neutropenia, Chronic idiopathic neutropenia, Severe Congenital Neutropenia (SCN), C-X-C chemokine receptor 4 (CXCR4), Congenital and acquired neutropenia, Autoimmune disease, Cohen syndrome, Barth syndrome, ELANE, G6PC3, GSD1b, Kostmann disease, Shwachman-Diamond syndrome, Autoimmune neutropenia (AIN)
Dichoptic Treatment for Amblyopia in Children 4 to 7 Years of Age (ATS23)
Jillian Bulman - jillian.bulman@cchmc.org
ALL
4 years to 7 years old
PHASE3
NCT06380517
At the time of enrollment, individuals must meet all the following inclusion criteria to be eligible to participate in the study.
• Age 4 to 7 years.
• Visual acuity, measured in each eye without cycloplegia in current refractive correction (if applicable) using the ATS-HOTV VA protocol on a study-approved device displaying single surrounded optotypes, as follows:
• VA in the amblyopic eye 20/40 to 20/200 inclusive.
• Age-normal VA in the fellow eye:44,45 • 4 years: 20/40 or better; 5-6 years: 20/32 or better; 7 years: 20/25 or better
• Interocular difference ≥ 3 logMAR lines (i.e., amblyopic eye VA at least 3 logMAR lines worse than fellow eye VA).
• Amblyopia associated with strabismus, anisometropia, or both (previously treated or untreated).
• Criteria for strabismic amblyopia: At least one of the following must be met: * Presence of a heterotropia on examination at distance or near fixation (with optical correction), must be \<=5 prism diopters (∆) by SPCT at distance and near fixation (see #7 below). * Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia).
• Criteria for anisometropia: At least one of the following criteria must be met: * ≥1.00 D difference between eyes in spherical equivalent (SE). * ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes.
• Criteria for combined-mechanism: Both of the following criteria must be met: * A criterion for strabismus is met (see above). * ≥1.00 D difference between eyes in spherical equivalent OR ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes.
• No more than 2 weeks (cumulative) of prior dichoptic treatment.
• No treatment with cycloplegic eyedrops (e.g., atropine) in the past 2 weeks; other treatments allowed up to enrollment but then must be discontinued.
• Refractive correction is required (single vision lenses or contact lenses) for any of the following refractive errors based on a cycloplegic refraction completed within the last 7 months: * Hypermetropia of 2.50 D or more by SE * Myopia of amblyopic eye of 0.50D or more SE * Astigmatism of 1.00D or more * Anisometropia of more than 0.50D SE NOTE: Monocular or binocular contact lens wear is allowed provided the contact lenses meet the refractive error correction requirements below. For each child, all testing must be performed using the same form of optical correction (i.e., no changing between contacts and spectacles).
• Spectacles/contact lens correction prescribing instructions referenced to the cycloplegic refraction completed within the last 7 months: * SE must be within 0.50D of fully correcting the anisometropia (if new glasses are prescribed, reduction in plus sphere must be symmetric in the two eyes). * SE must not be under corrected by more than 1.50D SE. * Cylinder power in both eyes must be within 0.50D of fully correcting the astigmatism. * Axis must be within +/- 10 degrees if cylinder power is ≤1.00D, and within +/- 5 degrees if cylinder power is \>1.00D. * Myopia must not be under corrected by more than 0.25D or over corrected by more than 0.50D SE, and any change must be symmetrical in the two eyes.
• Spectacles/contact lens correction (with or without other treatment such as patching) meeting the above criteria must be worn: * For at least 18 weeks OR until VA stability is documented (defined as \<0.1 logMAR change by the same testing method measured on 2 consecutive exams at least 9 weeks apart). * For determining VA stability (non-improvement): * The first of two measurements may be made 1) in current correction, or 2) in trial frames with or without cycloplegia or 3) without correction (if new correction is prescribed), * The second measurement must be made without cycloplegia in the correct spectacles/contact lens correction that has been worn for at least 9 weeks. * NOTE: Because this determination is a pre-randomization, the method of measuring VA is not mandated.
• Participant is willing to wear the Luminopia headset.
• Participant is willing to continue full-time spectacles/contact lens wear (if needed).
• Participant is willing to accept assignment to either dichoptic shows (view 1 hour per day 6 days per week) OR part-time patching (2 hours per day 7 days per week) for 26 weeks.
• Interpupillary distance of 52mm to 72mm inclusive.
• Investigator is willing to prescribe Luminopia or patching per protocol.
• Parent understands the protocol and is willing to accept randomization.
• Parent has phone (or access to phone) and is willing to be contacted by JAEB Center.
• Relocation outside area of active PEDIG site within the next 52 weeks is not anticipated. Individuals meeting any of the following criteria will be excluded from study participation.
• Heterotropia more than 5∆ at distance or near (measured by SPCT in current correction)
• Prism lenses or need of a prism prescription at enrollment.
• Current bifocal spectacles (eligible only if bifocal discontinued 2 weeks prior to enrollment).
• Myopia greater than -6.00D spherical equivalent in either eye.
• Previous intraocular or refractive surgery.
• Known skin reactions to patch or bandage adhesives.
• Ocular co-morbidity that may reduce VA determined by an ocular examination performed within the past 7 months (Note: nystagmus per se does not exclude the participant if the above visual acuity criteria are met using patch occlusion. Fogging is not permitted).
• Diplopia more than once per week over the last week prior to enrollment by parental report.
• History of light-induced seizures.
• Severe developmental delay that would interfere with treatment or evaluation (in the opinion of the investigator). Participants with mild speech delay or reading and/or learning disabilities are not excluded.
• Participation in a prior study involving patching for amblyopia
• Immediate family member (biological or legal guardian, child, sibling, parent) of investigative site personnel directly affiliated with this study or an employee of the JAEB center for Health Research.
• Age 4 to 7 years.
• Visual acuity, measured in each eye without cycloplegia in current refractive correction (if applicable) using the ATS-HOTV VA protocol on a study-approved device displaying single surrounded optotypes, as follows:
• VA in the amblyopic eye 20/40 to 20/200 inclusive.
• Age-normal VA in the fellow eye:44,45 • 4 years: 20/40 or better; 5-6 years: 20/32 or better; 7 years: 20/25 or better
• Interocular difference ≥ 3 logMAR lines (i.e., amblyopic eye VA at least 3 logMAR lines worse than fellow eye VA).
• Amblyopia associated with strabismus, anisometropia, or both (previously treated or untreated).
• Criteria for strabismic amblyopia: At least one of the following must be met: * Presence of a heterotropia on examination at distance or near fixation (with optical correction), must be \<=5 prism diopters (∆) by SPCT at distance and near fixation (see #7 below). * Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia).
• Criteria for anisometropia: At least one of the following criteria must be met: * ≥1.00 D difference between eyes in spherical equivalent (SE). * ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes.
• Criteria for combined-mechanism: Both of the following criteria must be met: * A criterion for strabismus is met (see above). * ≥1.00 D difference between eyes in spherical equivalent OR ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes.
• No more than 2 weeks (cumulative) of prior dichoptic treatment.
• No treatment with cycloplegic eyedrops (e.g., atropine) in the past 2 weeks; other treatments allowed up to enrollment but then must be discontinued.
• Refractive correction is required (single vision lenses or contact lenses) for any of the following refractive errors based on a cycloplegic refraction completed within the last 7 months: * Hypermetropia of 2.50 D or more by SE * Myopia of amblyopic eye of 0.50D or more SE * Astigmatism of 1.00D or more * Anisometropia of more than 0.50D SE NOTE: Monocular or binocular contact lens wear is allowed provided the contact lenses meet the refractive error correction requirements below. For each child, all testing must be performed using the same form of optical correction (i.e., no changing between contacts and spectacles).
• Spectacles/contact lens correction prescribing instructions referenced to the cycloplegic refraction completed within the last 7 months: * SE must be within 0.50D of fully correcting the anisometropia (if new glasses are prescribed, reduction in plus sphere must be symmetric in the two eyes). * SE must not be under corrected by more than 1.50D SE. * Cylinder power in both eyes must be within 0.50D of fully correcting the astigmatism. * Axis must be within +/- 10 degrees if cylinder power is ≤1.00D, and within +/- 5 degrees if cylinder power is \>1.00D. * Myopia must not be under corrected by more than 0.25D or over corrected by more than 0.50D SE, and any change must be symmetrical in the two eyes.
• Spectacles/contact lens correction (with or without other treatment such as patching) meeting the above criteria must be worn: * For at least 18 weeks OR until VA stability is documented (defined as \<0.1 logMAR change by the same testing method measured on 2 consecutive exams at least 9 weeks apart). * For determining VA stability (non-improvement): * The first of two measurements may be made 1) in current correction, or 2) in trial frames with or without cycloplegia or 3) without correction (if new correction is prescribed), * The second measurement must be made without cycloplegia in the correct spectacles/contact lens correction that has been worn for at least 9 weeks. * NOTE: Because this determination is a pre-randomization, the method of measuring VA is not mandated.
• Participant is willing to wear the Luminopia headset.
• Participant is willing to continue full-time spectacles/contact lens wear (if needed).
• Participant is willing to accept assignment to either dichoptic shows (view 1 hour per day 6 days per week) OR part-time patching (2 hours per day 7 days per week) for 26 weeks.
• Interpupillary distance of 52mm to 72mm inclusive.
• Investigator is willing to prescribe Luminopia or patching per protocol.
• Parent understands the protocol and is willing to accept randomization.
• Parent has phone (or access to phone) and is willing to be contacted by JAEB Center.
• Relocation outside area of active PEDIG site within the next 52 weeks is not anticipated. Individuals meeting any of the following criteria will be excluded from study participation.
• Heterotropia more than 5∆ at distance or near (measured by SPCT in current correction)
• Prism lenses or need of a prism prescription at enrollment.
• Current bifocal spectacles (eligible only if bifocal discontinued 2 weeks prior to enrollment).
• Myopia greater than -6.00D spherical equivalent in either eye.
• Previous intraocular or refractive surgery.
• Known skin reactions to patch or bandage adhesives.
• Ocular co-morbidity that may reduce VA determined by an ocular examination performed within the past 7 months (Note: nystagmus per se does not exclude the participant if the above visual acuity criteria are met using patch occlusion. Fogging is not permitted).
• Diplopia more than once per week over the last week prior to enrollment by parental report.
• History of light-induced seizures.
• Severe developmental delay that would interfere with treatment or evaluation (in the opinion of the investigator). Participants with mild speech delay or reading and/or learning disabilities are not excluded.
• Participation in a prior study involving patching for amblyopia
• Immediate family member (biological or legal guardian, child, sibling, parent) of investigative site personnel directly affiliated with this study or an employee of the JAEB center for Health Research.
DEVICE: Luminopia, OTHER: Eye Patch
Amblyopia
Dichoptic, Luminopia, Patching, movie
Quercetin Dyskeratosis Congenita (DC)/Telomere Biology Disorders (TBD)
Stephanie Edwards - stephanie.edwards@cchmc.org
ALL
2 years and over
PHASE1
NCT07628972
Inclusion Criteria:
• Diagnosis of DC/TBD deficiency as defined by at least one of the following: * Age adjusted mean-telomere length of \<1 percentile in all tested peripheral blood cells such as granulocytes, lymphocytes, B-cells, naïve T-cells, memory T-cells, and NK cells * A pathogenic or likely pathogenic mutation in DKC1, TERC, TERT, NOP10, NHP2, TINF2, CTC1, PARN, RTEL1, ACD, NAF1, ZCCHC8, or WRAP53
• Patients ≥ 2.0 years of age\* * The first three enrolled patients must be ≥ 10.0 years of age
• Able to take medication orally
Exclusion Criteria:
• Renal failure requiring dialysis
• Total bilirubin \>3 mg/dl and/or SGPT \>300 at time of enrollment, unless elevation thought to be related to DC/TBD
• Patients who have received quercetin or any over-the-counter antioxidant supplementation within last 1 month
• Patients currently taking androgen therapy
• Patients receiving digoxin therapy, who are unable to discontinue treatment due to medical reasons
• Patients receiving fluoroquinolone therapy, who are unable to discontinue treatment due to medical reasons
• Patients who are pregnant or breastfeeding or are at risk of pregnancy and are unable to use acceptable methods of birth control during the length of the study
• Patients with morphologic or cytogenetic evidence of myelodysplasia or leukemia.
• Patients needing to start or actively receiving radiation therapy, chemotherapy or immunotherapy for treatment of SCC or other cancers.
• Patients with unstable disease status or other medical issues requiring hospitalization or rapid escalation of medical care
• Participating in another therapeutic study for DC/TBD
• Patients who are in the early post-stem cell transplant period (i.e. first 6 months post-transplant)
DRUG: Quercetin
Dyskeratosis Congenita, Telomere Disease
Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study (TSC-STEPS)
Molly Griffith - Molly.Griffith@cchmc.org
ALL
1 day to 6 months old
PHASE2
NCT05104983
Inclusion Criteria:
• 0-6 months of age at the time of enrollment (subject must be \<7 months of chronological age at time of randomization and treatment initiation). Corrected age must be at least 39 weeks (calculated by subtracting the number of weeks born before 40 weeks gestation from the chronological age).
• Has a confirmed diagnosis of TSC based on established clinical or genetic criteria
Exclusion Criteria:
• Prior history of seizures (clinical or electrographic) at the time of enrollment or identified on baseline EEG.
• Has been treated in the past or is currently being treated at the time of enrollment with conventional anticonvulsant medications (AEDs), systemic (oral) mTOR inhibitors (such as rapamycin, sirolimus, or everolimus), ketogenic-related special diet, or another anti-seizure therapeutic agent, device, or procedure.
• Has taken any other investigational drug as part of another research study, within 30 days prior to the baseline screening visit.
• Has a significant illness or active infection at the time of the baseline screening visit
• Has a history of significant prematurity, defined as gestational age \<30 weeks at the time of delivery, or other significant medical complications at birth or during the neonatal period that other than TSC would convey additional risk of seizures or neurodevelopmental delay (i.e. HIE, severe neonatal infection, major surgery, prolonged ventilatory or other life-saving supportive care or procedures).
• Abnormal laboratory values at baseline (i.e., renal function, liver function, or bone marrow production) that are in the opinion of the investigator clinically significant and may jeopardize the safety of the study subject.
• Prior, planned or anticipated neurosurgery within 3 months of the baseline visit
• Has a TSC-associated condition for which mTOR treatment is clinically indicated (i.e. SEGA or AML).
• Subjects who are, in the opinion of the investigator, unable to comply with the requirements of the study.
DRUG: Sirolimus, DRUG: Placebo
Tuberous Sclerosis Complex, Epilepsy
Tuberous Sclerosis Complex, TSC, epilepsy, prevention, mTOR, sirolimus, infant
Observational Study of THC Concentrations in Acute Cannabis-induced CNS Depression
Allison Ackermann - allison.ackermann@cchmc.org
ALL
NCT06017622
Inclusion Criteria:
•
Inclusion Criteria:
The patient is younger than 18 years old.
• The patient visits the ED with signs and symptoms of suspected acute cannabis-induced CNS depression, as evidenced by the patient suffering from clinically significant CNS depression combined with the following criteria: a) Exposure to cannabis or cannabis-derived products, or other products containing any CB1 agonist (such as Δ8-THC, HHC) within the last 12 hours, confirmed through one or more of the following: i. Positive toxicology testing, or ii. Other clinical evidence, such as reliable collateral history (e.g., from caregivers, EMS personnel, or witnesses), physical evidence (e.g., product packaging), or a consistent self-report. AND EITHER b) Symptoms are associated with cannabis exposure and developed during, or shortly after, cannabis exposure; OR c) In the judgment of investigator or designated clinician, the presentation includes symptoms consistent with acute cannabis-induced CNS depression (e.g. respiratory rate depression, increased sedative effects).
• Blood samples are taken as part of routine clinical procedures, or the patient has an IV line through which blood can be taken.
• The LAR is willing and able to provide consent.
• The patient is willing and able to provide assent, if applicable and feasible, based on age and clinical condition. Exclusion criteria A potential patient who meets any of the following criteria will be excluded from participation in this study:
• Anything that, in the opinion of the PI, would place the patient at increased risk or preclude the patient's compliance with or completion of the study.
• Patient is presenting with signs or symptoms that are better explained by another medical condition or mental disorder, exposure to a drug other than cannabis, and, at the PI's discretion, are not induced by acute cannabis exposure.
• Patient presenting with cannabis use disorder (CUD), cannabis hyperemesis syndrome (CHS) or cannabis withdrawal syndrome (CWS)
• Patients who are brought in by law enforcement, i.e., cannabis intoxication associated with a vehicle accident (driving under the influence).
Acute Cannabis-induced CNS Depression
Overlapping Pain Trajectory Study (COPC)
Catherine Jackson - catherine.jackson@cchmc.org
ALL
10 years to 19 years old
NCT05752396
Inclusion Criteria:
• General Criteria * Access to the internet either by laptop, tablet, or phone (for REDCap Surveys) * English-speaking * Parent or guardian willing to comply with protocol, complete study assessments, and provide written informed consent
• Control Specific Criteria * No history/active chronic pain
• Patient Specific Criteria * Patients will need a diagnosis of a chronic pain derived congruent with ICD-11 criteria related to headache (migraine, daily headache), abdominal (FAPD), localized MSK (single limb/joint, low back or chest pain), or diffuse MSK (widespread MSK pain) * If on medications, they need to be on stable doses of prescribed pain and/or psychiatric medications for 4 weeks before the baseline study visit.
Exclusion Criteria:
• General Criteria * Skin conditions (e.g., eczema) or past skin damage on the arms and legs in or near sites of sensory testing * Any comorbid rheumatic disease (e.g., arthritis, lupus), neurological (e.g., epilepsy, traumatic brain injury) or medical condition (e.g., cancer, diabetes)
• Control Specific Criteria * Taking medications that can alter pain sensitivity (e.g., NSAIDs, opioids, stimulants, anticonvulsants; psychiatric)
• Patient Specific Criteria * Present psychiatric disease as defined by DSM IV (e.g. psychosis, bipolar disorder, major depression, generalized anxiety disorder), alcohol or drug dependence, or documented developmental delays or impairments (e.g., autism, cerebral palsy, ADHD, or mental retardation) that, in the opinion of the investigator, would interfere with adherence to study requirements or safe participation in the study
OTHER: Conditioned Pain Modulation, OTHER: Offset Analgesia, OTHER: Spatial Summation, OTHER: Temporal Summation
Migraine, Musculoskeletal Pain, Functional Abdominal Pain Disorders, Chronic Pain, Widespread Chronic Pain, Low Back Pain, Healthy Volunteers
TSC Biosample Repository and Natural History Database
Salma Ihiri - salma.ihiri@cchmc.org
ALL
NCT05676099
Inclusion Criteria:
* Diagnosis of tuberous sclerosis complex or lymphangioleiomyomatosis (sporadic LAM).
Exclusion Criteria:
\- PROCEDURE: Phlebotomy, PROCEDURE: Buccal (cheek) swab, GENETIC: Genetic Testing, OTHER: Tissue donation after routine clinical procedure
Tuberous Sclerosis, Lymphangioleiomyomatosis
A Phase 3 Trial to Compare IV BCV Versus IV CDV for Treatment of Adenovirus Infection After Allo-HCT (ENOVIA)
Brady Landon - brady.landon@cchmc.org
ALL
2 month(s) and over
PHASE3
NCT07387367
Inclusion Criteria:
• Male and female, post-allo HCT within last 180 days, aged 2 months and older at time of signing informed consent form.
• Subject/Guardian willing and able to understand and provide written informed consent to participate in the study.
• In the investigator's judgement, the subject's clinical condition justifies treatment with IV BCV or IV CDV for AdV infection.
• Has adenoviremia, based on any of: * AdV viremia DNA ≥10,000 IU/mL, OR * Two consecutive and rising AdV viremia DNA results of ≥1,000 IU/mL at screening, OR * AdV viremia DNA of ≥1,000 IU/mL, AND 1\. Lymphocyte count \<180/mm3, OR 2. Received T cell depletion, cord blood, or haploidentical transplant, OR 3. prior alemtuzumab, OR 4. anti-thymocyte globulin (ATG)
Exclusion Criteria:
• Subject received an allo-HCT with a matched sibling donor
• Subject received more than 5 mg/kg of CDV for any reason in the 21 days prior to first dose of study drug.
• Subject is allergic or hypersensitive to IV BCV or IV CDV or any of their components.
• Subject received anti-AdV-specific cell-based therapy within 3 weeks prior to W1D1 or an anti-AdV vaccine at any time.
• Subject has participated in any other investigational study within 30 days (or within 5.5 half-lives of the investigational product, whichever is longer) before signing the informed consent form (ICF), is currently participating in another interventional treatment trial with an investigational agent or is using an investigational device at the time of Screening.
DRUG: cidofovir, DRUG: Brincidofovir
Adenovirus Infections
Brincidofovir, Cidofovir, Adenovirus, allo-HCT, BCV-PA02, ENOVIA
Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP)
Abigayle Gibson - abigayle.gibson@cchmc.org
ALL
2 days to 17 years old
NA
NCT05376267
Inclusion criteria:
* Age 2 days to \< 18 years with corrected gestational age of at least 38 weeks
* Chest compressions for at least 2 minutes
* Coma or encephalopathy after resuscitation from Out-of-Hospital Cardiac Arrest (OHCA)
* Requires continuous mechanical ventilation through endotracheal tube or tracheostomy
* Definitive temperature control device initiated
* Randomization within 6 hours of Return of Spontaneous Circulation (ROSC)
* Informed consent from Legally Authorized Representative (LAR) including intent to maintain life support for 120 hours
Exclusion criteria:
* Glasgow Coma Motor Score (GCMS) = 6
* LAR does not speak English or Spanish
* Duration of Cardiopulmonary Resuscitation (CPR) \> 60 minutes
* Severe hemodynamic instability with continuous infusion of epinephrine or norepinephrine of 2 micrograms per kilogram per minute (μg/kg/minute) or initiation of Extracorporeal membrane oxygenation (ECMO)
* Pre-existing severe neurodevelopmental deficits with Pediatric Cerebral Performance Category (PCPC) =5 or progressive degenerative encephalopathy
* Pre-existing terminal illness, unlikely to survive to one year
* Cardiac arrest associated with brain, thoracic, or abdominal trauma
* Active and refractory severe bleeding prior to randomization
* Extensive burns or skin lesions incompatible with surface cooling
* Planned early withdrawal of life support before 120 hours
* Sickle cell anemia
* Pre-existing cryoglobulinemia
* Non-fatal drowning in ice covered water
* Central nervous system tumor with ongoing chemotherapy
* Previous enrollment in P-ICECAP trial
* Prisoner
* Chronic hypothermia
* New post-cardiac arrest diabetes insipidus
* Pregnancy
DEVICE: Therapeutic Hypothermia
Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced, Hypoxia-Ischemia, Brain
Bayesian Adaptive Clinical Trial, Hypothermia, therapeutic, Coma, Pediatric
ESIS in Pediatric DRE
Molly Griffith - molly.griffith@cchmc.org
ALL
1 year to 30 years old
NCT05469373
Inclusion Criteria:
* Diagnosis of drug-refractory epilepsy (DRE)
* 1-30 years of age
* recommended to undergo stereoencephalography (sEEG) at CCHMC
Exclusion Criteria:
* \<1 and \>30 years of age Epilepsy
epilepsy surgery, drug-resistant epilepsy, tuberous sclerosis