Clinical Trial in 22q13 Deletion Syndrome(Phelan-McDermid Syndrome)

This study is ongoing, but not recruiting participants.
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Alexander Kolevzon, Icahn School of Medicine at Mount Sinai Identifier:
First received: February 1, 2012
Last updated: January 26, 2016
Last verified: January 2016
The purpose of this study is to pilot the use of Insulin-Like Growth Factor-1 (IGF-1) treatment in 22q13 Deletion Syndrome (Phelan-McDermid Syndrome) caused by SHANK3 gene deficiency in order to evaluate safety, tolerability, and efficacy. IGF-1 is an injection under the skin that contains human IGF-1. IGF-1 is approved by the FDA under the brand name Increlex for the treatment of children with short stature due to primary IGF-1 deficiency. It is being used off-label in the current study and is not FDA approved, nor has it yet been studied in humans for the treatment of SHANK3 deficiency.

Condition Intervention Phase
22q13 Deletion Syndrome
Phelan-McDermid Syndrome
Drug: Insulin-Like Growth Factor-1 (IGF-1)
Drug: Normal saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind Placebo-Controlled Crossover Trial of Insulin-Like Growth Factor-1 (IGF-1) in Children and Adolescents With 22q13 Deletion Syndrome(Phelan-McDermid Syndrome)

Resource links provided by NLM:

Further study details as provided by Icahn School of Medicine at Mount Sinai:

Primary Outcome Measures:
  • Aberrant Behavior Checklist - Social Withdrawal (ABC-SW) subscale [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Repetitive Behavior Scale [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • CGI-Improvement and Severity Scales [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Caregiver Strain Index [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Exploratory outcomes [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Expressive language, social orienting, and motor skills,

Enrollment: 20
Study Start Date: February 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Insulin-Like Growth Factor-1 (IGF-1)
Drug: Insulin-Like Growth Factor-1 (IGF-1)
IGF-1 and placebo will each be administered for 3 months with a four-week washout period in between. IGF-1 will be administered for 3 months subcutaneously.
Other Name: Mecasermin; Increlex
Placebo Comparator: Normal saline
Drug: Normal saline
Saline solution will be administered for three months subcutaneously.
Other Name: Placebo

Detailed Description:

Overall, there will be 1-3 screening visits, a baseline visit where study drug will first be administered, and then 10 follow-up visits. Follow-up visits will occur at week 2, week 4, week 8, and week 12 in each treatment phase (IGF-1 or placebo), and then again 4 weeks after study completion, Parents/guardians will be asked to administer the IGF-1/ placebo by injection at home and will also be responsible for monitoring glucose levels in the child. Parents/guardians will be trained in these methods, and will have scheduled phone calls and appointments where the dose and tolerability will be discussed.

Assessments include the following:

  • Physical and neurological examination
  • Medical and psychiatric history
  • X-ray of long bone (e.g., hand) to ensure your child's growth plates are not closed
  • Electrocardiography
  • Echocardiography
  • Pregnancy test if applicable
  • Lab safety measures (through blood draw)
  • Autism Diagnostic Interview (ADI)
  • Autism Diagnostic Observation Schedule (ADOS)
  • The Mullen Scales of Early Learning or the Leiter International Performance Scale-Revised
  • Vineland Adaptive Behavior Scale (VABS)
  • Clinical Global Impressions (CGI) Rating Scales
  • The Repetitive Behaviors Scale (RBS)
  • Aberrant Behavior Checklist (ABC)
  • The Caregiver Strain Questionnaire (CSI)
  • Language Environment Analysis (LENA)
  • The Macarthur-Bates Communication Inventory (MCDI)
  • Unified Parkinson's Disease Rating Scale (UPDRS)
  • Quick Neurological Screening Test 2nd Edition (QNST-2)
  • Gait Analysis with motion capture video systems and interactive 3-dimensional modeling systems

Ages Eligible for Study:   5 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 5 to 12 years old
  • pathogenic deletions or mutations of the SHANK3 gene
  • minimum raw score of 12 on the Aberrant Behavior Checklist-Social Withdrawal subscale (ABC-SW)
  • stable medication regimens for at least three months prior to enrollment

Exclusion Criteria:

  • closed epiphyses
  • active or suspected neoplasia
  • intracranial hypertension
  • hepatic insufficiency
  • renal insufficiency
  • cardiomegaly / valvulopathy
  • history of allergy to IGF-1 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 deemed too medically compromised to tolerate the risk of experimental treatment with IGF-1
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01525901

United States, New York
Seaver Austin Center, Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
National Institute of Mental Health (NIMH)
Principal Investigator: Alexander Kolevzon, MD Icahn School of Medicine at Mount Sinai
  More Information

Additional Information:
Responsible Party: Alexander Kolevzon, Principal Investigator, Icahn School of Medicine at Mount Sinai Identifier: NCT01525901     History of Changes
Other Study ID Numbers: GCO 12-0929  IF# 1358648  1R34MH100276-01  GCO 11-1555  R34MH100276 
Study First Received: February 1, 2012
Last Updated: January 26, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Icahn School of Medicine at Mount Sinai:

Additional relevant MeSH terms:
Chromosome Deletion
Chromosome Disorders
Chromosome Aberrations
Congenital Abnormalities
Genetic Diseases, Inborn
Pathologic Processes
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action processed this record on May 24, 2016