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.

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.

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

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Immediately following publication. No end date.

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).

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.