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

NCT ID: NCT01525901

Last Updated: 2022-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2016-08-23

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.

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

Conditions

22q13 Deletion Syndrome; Phelan-McDermid Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Insulin-Like Growth Factor-1 (IGF-1)

Injection

Group Type: EXPERIMENTAL

Insulin-Like Growth Factor-1 (IGF-1)

Intervention Type: DRUG

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.

Normal saline

Injection

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: DRUG

Saline solution will be administered for three months subcutaneously.

Interventions

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.

Intervention Type: DRUG

Normal saline

Saline solution will be administered for three months subcutaneously.

Intervention Type: DRUG

Other Intervention Names

Mecasermin; Increlex; Placebo

Eligibility 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

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Alexander Kolevzon

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alexander Kolevzon, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Seaver Austin Center, Icahn School of Medicine at Mount Sinai

New York, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 25685306 (View on PubMed)

Kolevzon A, Breen MS, Siper PM, Halpern D, Frank Y, Rieger H, Weismann J, Trelles MP, Lerman B, Rapaport R, Buxbaum JD. Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome. Mol Autism. 2022 Apr 8;13(1):17. doi: 10.1186/s13229-022-00493-7.

Reference Type: DERIVED

PMID: 35395866 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.shank3gene.org

SHANK3 gene

https://pmsf.org/

Phelan-McDermid Syndrome Foundation

Other Identifiers

IF# 1358648

Identifier Type: -

Identifier Source: secondary_id

1R34MH100276-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GCO 11-1555

Identifier Type: OTHER

Identifier Source: secondary_id

R34MH100276

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GCO 12-0929

Identifier Type: -

Identifier Source: org_study_id