Phelan-McDermid SyndromePhase 2NCT05187377
A Controlled Trial of Growth Hormone in Phelan-McDermid Syndrome and Idiopathic Autism
A Phase 2 study testing Growth Hormone and Saline in people with Phelan-McDermid Syndrome and Autism Spectrum Disorder (ASD), run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 12 years
- Conditions the study is for
- Phelan-McDermid Syndrome, Autism Spectrum Disorder (ASD)
- What is being tested?
- Growth Hormone and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jan 2022to 5 Feb 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- Closed epiphyses
- Active or suspected neoplasia
- Intracranial hypertension
- Hepatic insufficiency
- Renal insufficiency
- Cardiomegaly/valvulopathy
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Seaver Autism Center for Research & Treatment
New York, New York, 10029
About this study
Official title: Electrophysiological Markers for Interventions in Phelan-McDermid Syndrome and Idiopathic Autism
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.
Read the 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.
- Being tested
- Growth Hormone, Saline
- Keywords
- Autism Spectrum Disorder, Phelan-McDermid Syndrome, 22q13 deletion Syndrome, Growth Hormone, Insulin-Like Growth Factor-1, Electrophysiology
- Medical subject headings
- Telomeric 22q13 Monosomy Syndrome, Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Growth HormoneDrug
Also called rhGH
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.
SalineDrug
Also called placebo
Placebo (saline) will be administered subcutaneously once daily.
| Study group | Role | What they receive |
|---|---|---|
| Growth Hormone then Saline | Experimental | 12 weeks in each treatment phase (rhGH then placebo) and a four week wash-out period between phases. Receives: Drug: Growth Hormone |
| Placebo (saline) then Growth Hormone | Placebo comparator | 12 weeks in each treatment phase (placebo then rhGH) and a four week wash-out period between phases. Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After 12 weeks of growth hormone therapy
Secondary outcomes (4)
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.
Measured: After 12 weeks of growth hormone therapy
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.
Measured: After 12 weeks of growth hormone therapy
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.
Measured: After 12 weeks of growth hormone therapy
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.
Measured: After 12 weeks of growth hormone therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2022
- Study start19 Jan 2022
- Primary completion28 Jan 2025
- Study completion5 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Phelan-McDermid SyndromeStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Alexander Kolevzon, Icahn School of Medicine at Mount Sinai
- Investigators
- Alexander Kolevzon, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05187377
- Sponsor's protocol ID
- STUDY-18-00245
- Other IDs
- R01NS105845, GCO 17-1159
- Status last verified
- Apr 2025
- First submitted
- 28 Dec 2021
- Last updated
- 20 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).