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

Mount Sinai Health System

Status and phase: Completed; Phase 2

Conditions: 22q13 Deletion Syndrome; Phelan-McDermid Syndrome

Treatments: Drug: Insulin-Like Growth Factor-1 (IGF-1); Drug: Normal saline

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01525901

R34MH100276 (U.S. NIH Grant/Contract)

GCO 12-0929

1R34MH100276-01 (U.S. NIH Grant/Contract)

IF# 1358648

GCO 11-1555 (Other Identifier)

Details and patient eligibility

About

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.

Full 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

Enrollment: 19 patients

Sex: All

Ages: 5 to 12 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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19 participants in 2 patient groups, including a placebo group

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

Experimental group

Description:

Injection

Treatment:

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

Normal saline

Placebo Comparator group

Description:

Injection

Treatment:

Drug: Normal saline