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

Phase 2

Terminated

Conditions: Autism Spectrum Disorder

Interventions: Drug: Placebo/saline
Drug: IGF-1

Registration Number: NCT01970345

Lead Sponsor: Icahn School of Medicine at Mount Sinai

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

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 & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo/saline	Placebo
IGF-1	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.

Primary Outcome Measures

Name	Time	Method
Aberrant Behavior Checklist - Social Withdrawal Subscale	Phase 1 - Week 4 and 12, Phase 2 - Week 4 and 8	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.

Secondary Outcome Measures

Name	Time	Method
The Clinical Global Impression - Severity Scale (CGI-S)	Phase 1 - Week 4 and 12, Phase 2 - Week 4 and 8	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).
Caregiver Strain	Phase 1 - Week 4 and 12, Phase 2 - Week 4 and 8	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.
Vineland Adaptive Behavior Composite Score	Baseline and Phase 1 Week 12	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.
Children's Yale-Brown Obsessive Compulsive Disorder Scale for Pervasive Developmental Disorders	Phase 1 - Week 4 and 12, Phase 2 - Week 4 and 8	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.
Social Pervasive Developmental Disorder-Behavior Inventory (PDDBI)	Week 8 of Phase 2	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.
Repetitive Behavior	Phase 1 - Week 4 and 12, Phase 2 - Week 4 and 8	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.