Clinical trial NCT01525901: Clinical Trial in 22q13 Deletion Syndrome(Phelan-McDermid Syndrome)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 22q13 Deletion Syndrome
Phelan-McDermid Syndrome
Keywords: SHANK3
IGF-1
Autism
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2012-02-03
Enrollment: 19
Sex: ALL
Minimum age (years): 5
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Change in Aberrant Behavior Checklist - Social Withdrawal (ABC-SW) Subscale - Study 1
timeFrame: Baseline and Week 12
measure: Change in Aberrant Behavior Checklist - Social Withdrawal (ABC-SW) Subscale Study 2
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change in Repetitive Behavior Scale - Study 2
timeFrame: Baseline and Week 12
measure: Change in CGI-Improvement and Severity Scales; - Study 2
timeFrame: Baseline and Week 12
measure: Change in Caregiver Strain Questionnaire
timeFrame: Baseline and Week 12
measure: Change in Sensory Profile (SP) - Study 2
timeFrame: Baseline and Week 12
measure: Change in Short Sensory Profile (SSP) - Study 2
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Seaver Austin Center, Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Alexander Kolevzon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.