Clinical trial NCT05187377: 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
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2022-01-11
Enrollment: 32
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Visual Evoked Potentials (VEP)
timeFrame: After 12 weeks of growth hormone therapy
Secondary outcomes:
measure: Aberrant Behavior Checklist (ABC) Social Withdrawal Subscale
timeFrame: After 12 weeks of growth hormone therapy
measure: Repetitive Behavior Scale-Revised (RBS-R)
timeFrame: After 12 weeks of growth hormone therapy
measure: Sensory Profile
timeFrame: After 12 weeks of growth hormone therapy
measure: Sensory Assessment for Neurodevelopmental Disorders (SAND)
timeFrame: After 12 weeks of growth hormone therapy
Other outcomes:
Locations:
city: New York
country: United States
facility: Seaver Autism Center for Research & Treatment
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Alexander Kolevzon, MD
role: PRINCIPAL_INVESTIGATOR
References: