Growth Hormone Treatment in Children With Phelan McDermid Syndrome

June 11, 2020 updated by: Swathi Sethuram

An Open Label Trial of Growth Hormone in Children and Adolescents With Phelan-McDermid Syndrome Targeting Social Withdrawal

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Seaver Autism Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 12 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Known pathogenic deletions or mutations in SHANK3 gene diagnosed by array CGH and/or direct sequencing.
  • Children between 2 and 12 years of age.
  • Open epiphyses on bone age x ray

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);
  • history of extreme prematurity (<1000 grams) with associated early neo-natal complications, e.g. intra-cerebral
  • hemorrhage, prolonged hypoxia, prolonged hypoglycemia;
  • patients with comorbid conditions who are deemed too medically compromised to tolerate the risk of experimental treatment with growth hormone.
  • Patient with visual problems that preclude the use of VEP's

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phelan-McDermid syndrome
Patients with Phelan-McDermid syndrome receive 12 weeks of growth hormone therapy
Drug: Recombinant human Growth hormone
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ABC - Social Withdrawal subscale
Time Frame: After 12 weeks of growth hormone therapy
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.
After 12 weeks of growth hormone therapy
Repetitive Behavior Scale-Revised (RBS-R)
Time Frame: After 12 weeks of growth hormone therapy
A 43 item instrument with total score from 0-129, with higher score indicating more restricted, repetitive and stereotyped behaviors.
After 12 weeks of growth hormone therapy
The Sensory Profile
Time Frame: After 12 weeks of growth hormone therapy
The full Sensory Profile has 125 items and the short version contains 38 items. Irritability; Lethargy/Social Withdrawal; Stereotypic Behavior; Hyperactivity; Inappropriate Speech. Parents use a Likert scale to rate how frequently their child demonstrates a particular behavior (ranging from 1 = always to 5 = never). Total scale for the Short Sensory Profile 38-190, with a lower score indicates greater deviation from typically developing children and indicates more sensory reactivity symptoms.
After 12 weeks of growth hormone therapy
The Sensory Assessment for Neurodevelopmental Disorders (SAND)
Time Frame: After 12 weeks of growth hormone therapy
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.
After 12 weeks of growth hormone therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual evoked potentials (VEP)
Time Frame: After 12 weeks of growth hormone therapy
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 (Zemon et al., 1986) which modulate excitatory and inhibitory signals received by the pyramidal cells.
After 12 weeks of growth hormone therapy
Change in Auditory event related potentials (AERP)
Time Frame: Baseline and 12 weeks of growth hormone therapy
AERP is useful for characterizing early processing of auditory tones and habituation to rapidly repeated stimuli as in speech processing. AERP amplitudes are measured at 12 weeks and compared to baseline.
Baseline and 12 weeks of growth hormone therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Swathi Sethuram

Investigators

  • Principal Investigator: Swathi Sethuram, MD, Icahn School of Medicine at Mount Sinai
  • Study Director: Alexander Kolevzon, MD, Icahn School of Medicine at Mount Sinai
  • Study Director: Robert Rapaport, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 13, 2019

Primary Completion (Actual)

June 5, 2020

Study Completion (Actual)

June 5, 2020

Study Registration Dates

First Submitted

June 27, 2019

First Submitted That Met QC Criteria

June 27, 2019

First Posted (Actual)

July 1, 2019

Study Record Updates

Last Update Posted (Actual)

June 12, 2020

Last Update Submitted That Met QC Criteria

June 11, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 18-2549

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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