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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
22q13 Deletion Syndrome; Phelan-McDermid Syndrome	Drug: Insulin-Like Growth Factor-1 (IGF-1); Drug: Normal saline	Phase 2

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

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	35 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Quadruple (Participant, Care Provider, 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)
Study Start Date :	February 2012
Estimated Primary Completion Date :	April 2021
Estimated Study Completion Date :	April 2021

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Insulin-Like Growth Factor-1 (IGF-1); Injection	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; Injection	Drug: Normal saline; Saline solution will be administered for three months subcutaneously.; Other Name: Placebo

Outcome Measures

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Primary Outcome Measures :

1. Aberrant Behavior Checklist - Social Withdrawal (ABC-SW) subscale [ Time Frame: Week 12 ]

Secondary Outcome Measures :

1. Repetitive Behavior Scale [ Time Frame: Week 12 ]
2. CGI-Improvement and Severity Scales [ Time Frame: Week 12 ]
3. Caregiver Strain Index [ Time Frame: Week 12 ]
4. Exploratory outcomes [ Time Frame: Week 12 ]
   Expressive language, social orienting, and motor skills,

Eligibility Criteria

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Ages Eligible for Study:	5 Years to 12 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 5 to 12 years old
• pathogenic deletions or mutations of the SHANK3 gene
• 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

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Contacts

Contact: Jordana Norry	212-241-3072	jordana.norry@mssm.edu

Locations

United States, New York
Seaver Austin Center, Icahn School of Medicine at Mount Sinai	Recruiting
New York, New York, United States, 10029
Principal Investigator: Alexander Kolevzon, MD

Sponsors and Collaborators

Icahn School of Medicine at Mount Sinai

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:	Alexander Kolevzon, MD	Icahn School of Medicine at Mount Sinai

More Information

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Additional Information:

Seaver Autism Center 

SHANK3 gene 

Phelan-McDermid Syndrome Foundation 

Publications of Results:

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. Erratum in: Mol Autism. 2015;6:31.

Responsible Party:	Alexander Kolevzon, Principal Investigator, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier:	NCT01525901 History of Changes
Other Study ID Numbers:	GCO 12-0929; IF# 1358648; 1R34MH100276-01 ( U.S. NIH Grant/Contract ); GCO 11-1555 ( Other Identifier: Icahn School of Medicine at Mount Sinai ); R34MH100276 ( U.S. NIH Grant/Contract )
First Posted:	February 3, 2012
Last Update Posted:	August 2, 2018
Last Verified:	July 2018

Keywords provided by Alexander Kolevzon, Icahn School of Medicine at Mount Sinai:

SHANK3; IGF-1; Autism

Additional relevant MeSH terms:

Syndrome; Chromosome Deletion; Chromosome Disorders; Disease; Pathologic Processes; Monosomy; Aneuploidy; Chromosome Aberrations; Congenital Abnormalities; Genetic Diseases, Inborn	Insulin, Globin Zinc; Insulin; Mitogens; Mecasermin; Hypoglycemic Agents; Physiological Effects of Drugs; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Growth Substances