Growth Hormone Treatment in Children With Phelan McDermid Syndrome
Condition: Phelan McDermid Syndrome
MeSH terms: Chromosome Disorders; Syndrome; Chromosome Deletion
Study type: Interventional
Phase: Phase 2

Summary: 
      Phelan McDermid syndrome (PMS) is a rare genetic form of autism spectrum disorder (ASD) due
      to deletions or mutations in the SHANK3 gene. This is a pilot open labeled trial of growth
      hormone therapy in children with PMS targeting social withdrawal and repetitive behavior.
      This research study will include children with PMS between 2-12 years of age who will receive
      growth hormone daily for 12 weeks, if found to be eligible. The aim of this study is to
      evaluate the effect of growth hormone on behavioral outcomes such as the aberrant behavior
      checklist social withdrawal subscale (ABC-SW) and repetitive behavior scale- revised (RBS-R).
      The effects of growth hormone on visual evoked potentials will also be assessed. Growth
      hormone increases insulin like growth factor 1 (IGF-1) levels and a previous trial of IGF-1
      therapy in PMS children showed improvement in these behavioral scales. Growth hormone has
      been studied for decades with an excellent safety profile and fewer adverse effects compared
      to IGF-1 therapy in other conditions. Hence, this may be a viable therapeutic option. There
      is no treatment currently available for PMS and this trial is therefore extremely important.
    

Detailed description: 
      BACKGROUND: Phelan-McDermid syndrome (PMS) is a genetic form of autism spectrum disorder
      (ASD) associated with developmental delay and hypotonia. IGF-1 promotes brain vessel growth,
      neurogenesis, and synaptogenesis.

      The research team previous clinical trial of IGF-1 in patients with Phelan McDermid Syndrome
      has shown improvement in core ASD symptoms using the Aberrant Behavior Checklist (ABC) and
      the Repetitive Behavior Scale-Revised (RBS-R). Growth hormone (GH) binds to its receptor and
      initiates a cascade of events which directly increases synthesis and release of IGF-1 levels.
      HYPOTHESIS: The study team hypothesize that rise in IGF-1 stimulated by growth hormone (GH)
      administration should produce improvement in behavior in children and adolescents with PMS as
      previously demonstrated with use of IGF-1.

      RESEARCH PLAN: The study team seek to recruit 10 patients with PMS and administer growth
      hormone as once daily subcutaneous injections for 12 weeks at standard doses. The study team
      will monitor baseline anthropometric measures, laboratory parameters for growth, IGF-1
      levels, and bone age prior to therapy and continue to monitor safety laboratory parameters
      during and after therapy. The goal of therapy would be to maintain IGF-1 levels between 1-2SD
      above the mean for age and puberty. Evaluations will include validated behavioral scales.
      Visual evoked potentials (VEPs) will be used as biomarkers of visual sensory reactivity.
    

Intervention name(s): Recombinant human Growth hormone
Intervention type(s): Drug
Intervention description(s): Subcutaneous growth hormone injections given once daily at a dose between 0.15mg/kg/week to 0.47 mg/kg/week titrated based on IGF-1 levels in serum for a duration of 12 weeks.
Intervention MeSH terms: Hormones
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Phelan McDermid Syndrome; 22q13 deletion Syndrome; Growth hormone; Autism; Insulin like growth factor 1