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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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)
Actual Enrollment :	20 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
Actual Primary Completion Date :	September 2016
Actual Study Completion Date :	September 2016

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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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Locations

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)

Investigators

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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Seaver Autism Center 

SHANK3 gene 

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:	January 11, 2017
Last Verified:	October 2016

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