A Controlled Trial of Growth Hormone in Phelan-McDermid Syndrome and Idiopathic Autism

NCT05187377 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: STUDY-18-00245R01NS105845GCO 17-1159
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  After 12 weeks of growth hormone therapy

Secondary Outcomes (4)

• Aberrant Behavior Checklist (ABC) Social Withdrawal Subscale

  After 12 weeks of growth hormone therapy

• Repetitive Behavior Scale-Revised (RBS-R)

  After 12 weeks of growth hormone therapy

• Sensory Profile

  After 12 weeks of growth hormone therapy

• Sensory Assessment for Neurodevelopmental Disorders (SAND)

  After 12 weeks of growth hormone therapy

Study Arms (2)

Growth Hormone then Saline

EXPERIMENTAL

12 weeks in each treatment phase (rhGH then placebo) and a four week wash-out period between phases.

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.

Drug: Saline

Interventions

Growth Hormone DRUG

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.

Also known as: rhGH

Growth Hormone then Saline

Saline DRUG

Placebo (saline) will be administered subcutaneously once daily.

Also known as: placebo

Placebo (saline) then Growth Hormone

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Seaver Autism Center for Research & Treatment

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Telomeric 22q13 Monosomy Syndrome; Autism Spectrum Disorder

Interventions

Growth Hormone; Sodium Chloride

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Alexander Kolevzon, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Director, Seaver Autism Center for Research & Treatment

Model Details: 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.

Study Record Dates

• First Submitted: December 28, 2021
• First Posted: January 11, 2022
• Study Start: January 19, 2022
• Primary Completion: January 28, 2025
• Study Completion: February 5, 2025
• Last Updated: April 20, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Immediately following publication. No end date.
• 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).

Locations

US (1)