Back to resultsA Controlled Trial of Growth Hormone in Phelan-McDermid Syndrome and Idiopathic Autism
Primary Purpose
Phelan-McDermid Syndrome, Autism Spectrum Disorder (ASD)
Status
Enrolling by invitation
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Growth Hormone
Saline
Sponsored by
About this trial
This is an interventional treatment trial for Phelan-McDermid Syndrome focused on measuring Autism Spectrum Disorder, Phelan-McDermid Syndrome, 22q13 deletion Syndrome, Growth Hormone, Insulin-Like Growth Factor-1, Electrophysiology
Eligibility Criteria
Inclusion Criteria:
- Children between 2 and 12 years of age
- Open epiphyses on bone age x ray
- Must be on stable medication and psychosocial treatment regimens for at least three months prior to enrollment, assuming the concomitant medication is safe for use with Growth Hormone
- No prior use of Growth Hormone or IGF-1
- ASD group: Meet DSM-5 criteria for Autism Spectrum Disorder confirmed by the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2); absence of known pathogenic copy number variants
- PMS group: Known pathogenic deletions or mutations in SHANK3 gene diagnosed by array CGH and/or direct sequencing
Exclusion Criteria:
- Closed epiphyses
- Active or suspected neoplasia
- Intracranial hypertension
- Hepatic insufficiency
- Renal insufficiency
- Cardiomegaly/valvulopathy
- History of allergy to growth hormone or any component of the formulation (mecasermin)
- Patients with comorbid conditions who are deemed too medically compromised to tolerate the risk of experimental treatment with growth hormone (including severe obesity, sleep apnea, and various acute health conditions)
- Visual problems that preclude the use of VEP
Sites / Locations
- Seaver Autism Center for Research & Treatment
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Growth Hormone then Saline
Placebo (saline) then Growth Hormone
Arm Description
12 weeks in each treatment phase (rhGH then placebo) and a four week wash-out period between phases.
12 weeks in each treatment phase (placebo then rhGH) and a four week wash-out period between phases.
Outcomes
Primary Outcome Measures
Visual Evoked Potentials (VEP)
A noninvasive technique to evaluate the functional integrity of visual pathways in the brain from the retina to the visual cortex via the optic nerve/optic radiations. The VEP is recorded from the head's surface, over the visual cortex, and is extracted from ongoing EEG through signal averaging. VEPs reflect the sum of excitatory and inhibitory postsynaptic potentials occurring on apical dendrites which modulate excitatory and inhibitory signals received by the pyramidal cells.
Secondary Outcome Measures
Aberrant Behavior Checklist (ABC) Social Withdrawal Subscale
A caregiver report symptom checklist. 58-item instrument into 5 subscales: Irritability (score 0-45); Lethargy/Social Withdrawal (score 0-48); Stereotypic Behavior (score 0-21); Hyperactivity (score 0-48); Inappropriate Speech (score 0-12). Total scale 0-174, with higher score indicating more aberrant behavior.
Repetitive Behavior Scale-Revised (RBS-R)
A 43 item instrument with total score from 0-129, with higher score indicating more restricted, repetitive and stereotyped behaviors.
Sensory Profile
The Sensory Profile has 125 items. Parents use a Likert scale to rate how frequently their child demonstrates a particular behavior (ranging from 1 = always to 5 = never). Total scale from 125-625, with a lower score indicates greater deviation from typically developing children and indicates more sensory reactivity symptoms.
Sensory Assessment for Neurodevelopmental Disorders (SAND)
A clinician-administered assessment and corresponding caregiver interview that is not dependent on verbal or cognitive ability and is therefore appropriate for severely affected or nonverbal individuals with PMS. Responses are rated by a trained examiner on an algorithm. Scores are dichotomous, 0 (not present) or 1 (present) and are based on a summary of observed sensory behaviors throughout the duration of the observation. A total SAND score ranging from 0 to 90. Higher scores represent a higher level of sensory reactivity symptoms.
Full Information
NCT ID
NCT05187377
First Posted
December 28, 2021
Last Updated
October 6, 2023
Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
1. Study Identification
Unique Protocol Identification Number
NCT05187377
Brief Title
A Controlled Trial of Growth Hormone in Phelan-McDermid Syndrome and Idiopathic Autism
Official Title
Electrophysiological Markers for Interventions in Phelan-McDermid Syndrome and Idiopathic Autism
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
January 19, 2022 (Actual)
Primary Completion Date
March 1, 2024 (Anticipated)
Study Completion Date
March 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This clinical trial will use growth hormone as a novel treatment for Phelan-McDermid syndrome (PMS) and idiopathic autism. A double-blind, placebo-controlled crossover trial design will be used in 30 children with idiopathic autism and 15 children with PMS to evaluate the the effects of growth hormone on visual evoked potentials (VEPs), socialization, language, and repetitive behaviors. The researchers expect to provide evidence for the feasibility of using VEPs in PMS, and to show support for growth hormone in ameliorating clinical symptoms of ASD.
Detailed Description
This study will show that select electrophysiological markers in PMS are relevant to iASD and predictive of treatment response with growth hormone. The long-term goal is to optimize treatment selection in iASD by establishing biological signature(s) derived from PMS. The expected outcome is to establish the feasibility of electrophysiological biomarkers for use in clinical trials in PMS and iASD, demonstrate efficacy of growth hormone in PMS and iASD, and to define a biological profile that will mark a subset of patients with iASD likely to show clinical response to growth hormone.
The study will enroll 45 children (15 PMS; 30 iASD; age 2-12 years) and administer growth hormone/placebo as once daily subcutaneous injection for 12 weeks at standard doses. The study team will monitor baseline anthropometric measures, laboratory parameters for growth, IGF-1 levels, and bone age throughout the study. Evaluations will include validated behavioral scales. Visual evoked potentials (VEPs) will be used as biomarkers of visual sensory reactivity.
Growth Hormone is approved by the FDA for the treatment of children with short stature due to primary growth hormone deficiency, among several other indications. It is being used off-label in the current study and is not FDA approved for use in PMS or ASD.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Phelan-McDermid Syndrome, Autism Spectrum Disorder (ASD)
Keywords
Autism Spectrum Disorder, Phelan-McDermid Syndrome, 22q13 deletion Syndrome, Growth Hormone, Insulin-Like Growth Factor-1, Electrophysiology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
A randomized, double-blind, placebo-controlled, crossover design, with 12 weeks in each treatment phase (rhGH and placebo) and a four week wash-out period between phases.
During each phase, participants will be monitored at Baseline, Week 2, Week 4, Week 8, and Week 12.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Mount Sinai Pharmacy will be responsible for randomizing research participants and preparing investigational drug/placebo. The participant, caregivers, and study team will all remain blinded for the duration of the study.
Allocation
Randomized
Enrollment
45 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Growth Hormone then Saline
Arm Type
Experimental
Arm Description
12 weeks in each treatment phase (rhGH then placebo) and a four week wash-out period between phases.
Arm Title
Placebo (saline) then Growth Hormone
Arm Type
Placebo Comparator
Arm Description
12 weeks in each treatment phase (placebo then rhGH) and a four week wash-out period between phases.
Intervention Type
Drug
Intervention Name(s)
Growth Hormone
Other Intervention Name(s)
rhGH
Intervention Description
Growth hormone will be administered subcutaneously once daily. A starting dose of 0.15 mg/kg/week divided daily for 2 weeks to ensure safety and tolerance. The dose will then be increased to 0.3 mg/kg/week for 10 weeks. Doses will be titrated based on IGF-1 levels and monitored every four weeks up to a maximum dose of 0.45 mg/kg/week based on the package insert.
Intervention Type
Drug
Intervention Name(s)
Saline
Other Intervention Name(s)
placebo
Intervention Description
Placebo (saline) will be administered subcutaneously once daily.
Primary Outcome Measure Information:
Title
Visual Evoked Potentials (VEP)
Description
A noninvasive technique to evaluate the functional integrity of visual pathways in the brain from the retina to the visual cortex via the optic nerve/optic radiations. The VEP is recorded from the head's surface, over the visual cortex, and is extracted from ongoing EEG through signal averaging. VEPs reflect the sum of excitatory and inhibitory postsynaptic potentials occurring on apical dendrites which modulate excitatory and inhibitory signals received by the pyramidal cells.
Time Frame
After 12 weeks of growth hormone therapy
Secondary Outcome Measure Information:
Title
Aberrant Behavior Checklist (ABC) Social Withdrawal Subscale
Description
A caregiver report symptom checklist. 58-item instrument into 5 subscales: Irritability (score 0-45); Lethargy/Social Withdrawal (score 0-48); Stereotypic Behavior (score 0-21); Hyperactivity (score 0-48); Inappropriate Speech (score 0-12). Total scale 0-174, with higher score indicating more aberrant behavior.
Time Frame
After 12 weeks of growth hormone therapy
Title
Repetitive Behavior Scale-Revised (RBS-R)
Description
A 43 item instrument with total score from 0-129, with higher score indicating more restricted, repetitive and stereotyped behaviors.
Time Frame
After 12 weeks of growth hormone therapy
Title
Sensory Profile
Description
The Sensory Profile has 125 items. Parents use a Likert scale to rate how frequently their child demonstrates a particular behavior (ranging from 1 = always to 5 = never). Total scale from 125-625, with a lower score indicates greater deviation from typically developing children and indicates more sensory reactivity symptoms.
Time Frame
After 12 weeks of growth hormone therapy
Title
Sensory Assessment for Neurodevelopmental Disorders (SAND)
Description
A clinician-administered assessment and corresponding caregiver interview that is not dependent on verbal or cognitive ability and is therefore appropriate for severely affected or nonverbal individuals with PMS. Responses are rated by a trained examiner on an algorithm. Scores are dichotomous, 0 (not present) or 1 (present) and are based on a summary of observed sensory behaviors throughout the duration of the observation. A total SAND score ranging from 0 to 90. Higher scores represent a higher level of sensory reactivity symptoms.
Time Frame
After 12 weeks of growth hormone therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Children between 2 and 12 years of age
Open epiphyses on bone age x ray
Must be on stable medication and psychosocial treatment regimens for at least three months prior to enrollment, assuming the concomitant medication is safe for use with Growth Hormone
No prior use of Growth Hormone or IGF-1
ASD group: Meet DSM-5 criteria for Autism Spectrum Disorder confirmed by the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2); absence of known pathogenic copy number variants
PMS group: Known pathogenic deletions or mutations in SHANK3 gene diagnosed by array CGH and/or direct sequencing
Exclusion Criteria:
Closed epiphyses
Active or suspected neoplasia
Intracranial hypertension
Hepatic insufficiency
Renal insufficiency
Cardiomegaly/valvulopathy
History of allergy to growth hormone or any component of the formulation (mecasermin)
Patients with comorbid conditions who are deemed too medically compromised to tolerate the risk of experimental treatment with growth hormone (including severe obesity, sleep apnea, and various acute health conditions)
Visual problems that preclude the use of VEP
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexander Kolevzon, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seaver Autism Center for Research & Treatment
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
IPD Sharing Time Frame
Immediately following publication. No end date.
IPD Sharing Access Criteria
Anyone who wishes to access the data. Any purpose. Proposals should be directed to PI. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (tbd).
Learn more about this trial
A Controlled Trial of Growth Hormone in Phelan-McDermid Syndrome and Idiopathic Autism
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