Growth Hormone Treatment in Children With Phelan McDermid Syndrome

NCT04003207 | Completed Phase 2 Results FDA Drug

• 1 other identifier: GCO 18-2549
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Phelan McDermid Syndrome

Keywords

Phelan McDermid Syndrome; 22q13 deletion Syndrome; Growth hormone; Autism; Insulin like growth factor 1

Outcome Measures

Primary Outcomes (4)

• ABC - Social Withdrawal Subscale

  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)

  A 43 item instrument with total score from 0-129, with higher score indicating more restricted, repetitive and stereotyped behaviors. Subscales Stereotyped Behavior (0-27) Self-injurious Behavior (0-24) Compulsive Behavior (0-18) Ritualistic Behavior (0-36) Sameness Behavior (0-33) Restricted Behavior (0-12)

  After 12 weeks of growth hormone therapy

• The Sensory Profile

  The full Sensory Profile has 125 items and the short version contains 38 items. 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. Subscales Tactile (7-35) Taste / Smell (4-20) Movement (3-15) Sensation (7-35) Auditory (6-30) Low Energy / Weak (6-30) Visual / Auditory (5-25)

  After 12 weeks of growth hormone therapy

• The Sensory Assessment for Neurodevelopmental Disorders (SAND)

  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 Outcomes (2)

• Visual Evoked Potentials (VEP)

  After 12 weeks of growth hormone therapy

• Change in Auditory Event Related Potentials (AERP)

  Baseline and 12 weeks of growth hormone therapy

Study Arms (1)

Phelan-McDermid syndrome

EXPERIMENTAL

Patients with Phelan-McDermid syndrome receive 12 weeks of growth hormone therapy

Drug: Recombinant human Growth hormone

Interventions

Recombinant human Growth hormone DRUG

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.

Phelan-McDermid syndrome

Eligibility Criteria

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

You may qualify if:

• 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

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);
• 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

Sponsors & Collaborators

• Swathi Sethuram: lead

Study Sites (1)

Seaver Autism Center

New York, New York, 10029, United States

Location

Related Publications (6)

• Kolevzon A, Bush L, Wang AT, Halpern D, Frank Y, Grodberg D, Rapaport R, Tavassoli T, Chaplin W, Soorya L, Buxbaum JD. A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome. Mol Autism. 2014 Dec 12;5(1):54. doi: 10.1186/2040-2392-5-54. eCollection 2014.

  PMID: 25685306 BACKGROUND

• De Rubeis S, Siper PM, Durkin A, Weissman J, Muratet F, Halpern D, Trelles MDP, Frank Y, Lozano R, Wang AT, Holder JL Jr, Betancur C, Buxbaum JD, Kolevzon A. Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations. Mol Autism. 2018 Apr 27;9:31. doi: 10.1186/s13229-018-0205-9. eCollection 2018.

  PMID: 29719671 BACKGROUND

• Costales J, Kolevzon A. The therapeutic potential of insulin-like growth factor-1 in central nervous system disorders. Neurosci Biobehav Rev. 2016 Apr;63:207-22. doi: 10.1016/j.neubiorev.2016.01.001. Epub 2016 Jan 15.

  PMID: 26780584 BACKGROUND

• Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB, Rossi WC, Feudtner C, Murad MH; Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society. Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency. Horm Res Paediatr. 2016;86(6):361-397. doi: 10.1159/000452150. Epub 2016 Nov 25.

  PMID: 27884013 BACKGROUND

• Aramburo C, Alba-Betancourt C, Luna M, Harvey S. Expression and function of growth hormone in the nervous system: a brief review. Gen Comp Endocrinol. 2014 Jul 1;203:35-42. doi: 10.1016/j.ygcen.2014.04.035. Epub 2014 May 13.

  PMID: 24837495 BACKGROUND

• Sethuram S, Levy T, Foss-Feig J, Halpern D, Sandin S, Siper PM, Walker H, Buxbaum JD, Rapaport R, Kolevzon A. A proof-of-concept study of growth hormone in children with Phelan-McDermid syndrome. Mol Autism. 2022 Jan 29;13(1):6. doi: 10.1186/s13229-022-00485-7.

  PMID: 35093163 DERIVED

MeSH Terms

Conditions

Telomeric 22q13 Monosomy Syndrome; Autistic Disorder

Interventions

Growth Hormone

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; 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

Results Point of Contact

• Title: Alexander Kolevzon, MD
• Organization: Icahn School of Medicine at Mount Sinai

alexander.kolevzon@mssm.edu

(212) 659-9134

Study Officials

• Swathi Sethuram, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Alexander Kolevzon, MD

  Icahn School of Medicine at Mount Sinai

  STUDY DIRECTOR

• Robert Rapaport, MD

  Icahn School of Medicine at Mount Sinai

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Fellow, Division of Pediatric Endocrinology & Diabetes

Study Record Dates

• First Submitted: June 27, 2019
• First Posted: July 1, 2019
• Study Start: September 13, 2019
• Primary Completion: June 5, 2020
• Study Completion: June 5, 2020
• Last Updated: May 2, 2024
• Results First Posted: May 2, 2024

Record last verified: 2024-04

Locations

US (1)