A Pilot Treatment Study of Insulin-Like Growth Factor-1 (IGF-1) in Autism Spectrum Disorder

The proposed project will pilot the use of IGF-1 as a novel treatment for core symptoms of autism. We will use a double-blind, placebo-controlled crossover trial design in five children with autism to evaluate the impact of IGF-1 treatment on autism-specific impairments in socialization, language, and repetitive behaviors. We expect to provide evidence for the safety and feasibility of IGF-1 in ameliorating social withdrawal in children with Autistic Disorder. Further, we expect to demonstrate that IGF-1 is associated with improvement on secondary outcomes of social impairment, language delay, and repetitive behavior, as well as on functional outcomes of global severity.

Study Overview

• Status: Terminated
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: IGF-1; Drug: Placebo/saline

Detailed Description

IGF-1 is an FDA approved, commercially available compound that crosses the blood-brain barrier and has beneficial effects on synaptic development by promoting neuronal cell survival, synaptic maturation, and synaptic plasticity. IGF-1 is effective in reversing mouse and neuronal models of Rett syndrome and Phelan McDermid syndrome, both single gene causes of ASD and may therefore be effective in treating autism spectrum disorders (ASD) more broadly.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lexie Massa; Phone Number: 212-241-3692; Email: alexandra.massa@mssm.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Meet DSM-5 criteria for Autism Spectrum Disorder confirmed by the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule- Generic (ADOS-G)
• Children between the ages of 5-12 years of age
• Language delay (lack of fluent phrase speech) reflected by use of ADOS Module 1 or 2
• Must be on stable medication regimens for at least three months prior to enrollment, assuming the concomitant medication is safe for use with IGF-1

Exclusion Criteria:

• Closed epiphyses
• Active or suspected neoplasia
• Intracranial hypertension
• Hepatic insufficiency
• Renal insufficiency
• Cardiomegaly/valvulopathy
• History of allergy to IGF-1
• Patients with comorbid conditions deemed too medically compromised to tolerate the risk of experimental treatment with IGF-1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo/saline; Placebo; Other Names: Saline
Experimental: IGF-1; Randomized, placebo-controlled, crossover format with 12 weeks in each treatment arm (IGF-1 and placebo), separated by a four-week wash-out phase. Dose titration will be initiated at 0.04 mg/kg twice daily by subcutaneous injection, and increased, as tolerated, every week by 0.04 mg/kg per dose to a maximum of 0.12 mg/kg twice daily. Doses may be decreased according to tolerability by 0.04 mg/kg per dose. Medication will be administered twice daily with meals, and preprandial glucose monitoring will be performed by parents at treatment initiation, prior to each injection, and until a well tolerated dose is established.	Drug: IGF-1; IGF-1 is an FDA-approved (IND exemption #113450), commercially available compound that crosses the blood-brain barrier and has beneficial effects on synaptic development by promoting neuronal cell survival, synaptic maturation, and synaptic plasticity.; Other Names: Increlex; mecasermin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aberrant Behavior Checklist - Social Withdrawal Subscale	Aberrant Behavior Checklist - Social Withdrawal Subscale has16 items, Each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). Total Subscale scores range from 0 to 48. Higher score indicates poorer health outcomes.	Phase 1 - Week 4 and 12, Phase 2 - Week 4 and 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Social Pervasive Developmental Disorder-Behavior Inventory (PDDBI)	Social Pervasive Developmental Disorder-Behavior Inventory (PDDBI) - Each item is marked as "0" (does not show the behavior), "1" (rarely shows the behavior), "2" (sometimes/partially shows the behavior), "3" (usually/typically shows the behavior), or "?" (uncertain/don't understand). The Sensory, Ritual, Social Pragmatic, Semantic Pragmatic, Arouse, Specific Fears, and Aggressiveness subscales range from 0 to 100, where higher score indicates worse severity than the average child with autism. The Social Approach, Expressive, and Learning Memory subscales range from 0 to 100, where higher score indicates better skills relative to the average child with autism. Scores reported in subscales. Scores were not reported as full scale.	Week 4 of Phase 1
Social Pervasive Developmental Disorder-Behavior Inventory (PDDBI)	Social Pervasive Developmental Disorder-Behavior Inventory (PDDBI) - Each item is marked as "0" (does not show the behavior), "1" (rarely shows the behavior), "2" (sometimes/partially shows the behavior), "3" (usually/typically shows the behavior), or "?" (uncertain/don't understand). The Sensory, Ritual, Social Pragmatic, Semantic Pragmatic, Arouse, Specific Fears, and Aggressiveness subscales range from 0 to 100, where higher score indicates worse severity than the average child with autism. The Social Approach, Expressive, and Learning Memory subscales range from 0 to 100, where higher score indicates better skills relative to the average child with autism. Scores reported in subscales. Scores were not reported as full scale.	Week 12 of Phase 1
Social Pervasive Developmental Disorder-Behavior Inventory (PDDBI)	Social Pervasive Developmental Disorder-Behavior Inventory (PDDBI) - Each item is marked as "0" (does not show the behavior), "1" (rarely shows the behavior), "2" (sometimes/partially shows the behavior), "3" (usually/typically shows the behavior), or "?" (uncertain/don't understand). The Sensory, Ritual, Social Pragmatic, Semantic Pragmatic, Arouse, Specific Fears, and Aggressiveness subscales range from 0 to 100, where higher score indicates worse severity than the average child with autism. The Social Approach, Expressive, and Learning Memory subscales range from 0 to 100, where higher score indicates better skills relative to the average child with autism. Scores reported in subscales. Scores were not reported as full scale.	Week 4 of Phase 2
Social Pervasive Developmental Disorder-Behavior Inventory (PDDBI)	Social Pervasive Developmental Disorder-Behavior Inventory (PDDBI) - Each item is marked as "0" (does not show the behavior), "1" (rarely shows the behavior), "2" (sometimes/partially shows the behavior), "3" (usually/typically shows the behavior), or "?" (uncertain/don't understand). The Sensory, Ritual, Social Pragmatic, Semantic Pragmatic, Arouse, Specific Fears, and Aggressiveness subscales range from 0 to 100, where higher score indicates worse severity than the average child with autism. The Social Approach, Expressive, and Learning Memory subscales range from 0 to 100, where higher score indicates better skills relative to the average child with autism. Scores reported in subscales. Scores were not reported as full scale.	Week 8 of Phase 2
Repetitive Behavior	Repetitive Behavior: Repetitive Behavior Scale (RBS) - Includes 43 items scored 0 (behavior does not occur), 1 (behavior occurs and is a mild problem), 2 (behavior occurs and is a moderate problem), 3 (behavior occurs and is a severe problem). Full scale from 0-129, with higher scores indicating worse outcomes.	Phase 1 - Week 4 and 12, Phase 2 - Week 4 and 8
Caregiver Strain	Caregiver Strain Index - 21 question tool, with response 1 (not al all) - 5 (very much). Total score on scale from 21-105. Higher score indicates poorer health outcomes.	Phase 1 - Week 4 and 12, Phase 2 - Week 4 and 8
Children's Yale-Brown Obsessive Compulsive Disorder Scale for Pervasive Developmental Disorders	Clinician-rated interview designed to evaluate repetitive behavior in children with pervasive developmental disorders (PDDs). It is a modification of the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), developed to assess typically-developing children with obsessive compulsive behavior. Because of language limitations in children with PDDs the CY-BOCS-PDD only includes the five compulsion items: Time Spent, Interference, Distress, Resistance of repetitive behavior, and Control of repetitive behavior. Each item is rated from 0 (none) through 4 (extreme), and scores can range from 0 to 20, with higher scores reflecting more severe symptoms. Usually a score 8 is considered clinically significant.	Phase 1 - Week 4 and 12, Phase 2 - Week 4 and 8
The Clinical Global Impression - Severity Scale (CGI-S)	The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating. Full scale is 1 (normal, not at all ill) to 7 (extremely ill).	Phase 1 - Week 4 and 12, Phase 2 - Week 4 and 8
Vineland Adaptive Behavior Composite Score	The Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) yields an overall standard score (Adaptive Behavior Composite, ABC) and age standard scores in four domains. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160). Higher scores suggest a higher level of adaptive functioning.	Baseline and Phase 1 Week 12

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Autism Science Foundation
• Investigators: Principal Investigator: Alexander Kolevzon, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): September 13, 2017
• Study Completion (Actual): September 13, 2017

Study Registration Dates

• First Submitted: October 22, 2013
• First Submitted That Met QC Criteria: October 22, 2013
• First Posted (Estimated): October 28, 2013

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Autism Spectrum Disorder; IGF-1
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Physiological Effects of Drugs; Growth Substances; Mecasermin
• Other Study ID Numbers: GCO 13-1206