Dose Finding Study of Pioglitazone in Children With Autism Spectrum Disorders (ASD) (PIO)

NCT01205282 | Completed Phase 2

• 1 other identifier: 10-002
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose a pilot, single blind, placebo run-in, dose finding study of pioglitazone in children with autism with the ultimate goal of identifying appropriate dosing and outcome measures for a larger follow-up randomized placebo controlled clinical trial. The specific aims of this study are: 1) To examine the safety of pioglitazone in children with autism spectrum disorders (ASD) ages 5-12 years; 2) To identify appropriate outcome measures to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD; 3) To determine the maximum tolerated dose to be used in the follow-up multisite randomized controlled trial; 4) To examine the effect of pioglitazone on markers of inflammation (cytokine levels) and oxidative stress (superoxide dismutase, malonyl aldehydes); 5) To explore the relationship between different doses and response to treatment.

Conditions

Autism Spectrum Disorders

Keywords

ASD

Outcome Measures

Primary Outcomes (9)

• Safety of pioglitazone in children with ASD ages 5-12 years

  This will be measured by the Clinical Global Impressions - Improvement Scale - Global (CGI-I-Global)

  16 Weeks

• Safety of pioglitazone in children with ASD ages 5-12 years

  This will be measured by the Safety Monitoring Uniform Report Form (SMURF)

  16 Weeks

• Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD

  This will be measured by the Aberrant Behavior Checklist (ABC)

  16 Weeks

• Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD

  This will be measured the Social Responsiveness Scale (SRS)

  16 Weeks

• Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD

  This will be measured by the the Child Yale-Brown Obsessive-Compulsive Scale (CY-BOCS)

  16 Weeks

• Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD

  This will be measured by the Repetitive Behavior Scale - Revised (RBS-R)

  16 Weeks

• Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD

  This will be measured by the Behavioral Assessment System for Children (BASC-2)

  16 Weeks

• Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD

  This will be measured by the Child and Adolescent Symptom Inventory (CASI) - Anxiety Subscale

  16 Weeks

• Maximum tolerated dose to be used in the follow-up multisite randomized controlled trial

  Maximum Tolerated Dose (MTD)

  16 Weeks

Secondary Outcomes (2)

• Efficacy of pioglitazone on markers of inflammation (cytokine levels) and oxidative stress (superoxide dismutase, malonyl aldehydes)

  16 Weeks

• Relationship between different doses and response to treatment

  16 Weeks

Study Arms (2)

Pioglitazone

EXPERIMENTAL

A modified dose finding method will be used to determine safety and dose response among three dose levels (0.25mg/kg QD, 0.5mg/kg QD, and 0.75mg/kg QD). There will be 14 weeks of active treatment.

Drug: Pioglitazone

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Pioglitazone DRUG

A modified dose finding method will be used to determine safety and dose response among three dose levels (0.25mg/kg QD, 0.5mg/kg QD, and 0.75mg/kg QD). The dose has been based on the per weight maximum adult dose. Specifically, the FDA has approved 45mg as the maximum adult dose. For a 60kg adult, this is 0.75mg/kg. There will be 14 weeks of active treatment.

Pioglitazone

Placebo DRUG

There will be a 2 week period of placebo run-in.

Placebo

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female outpatients 5-12 years of age inclusive (see Note below).
• Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV) criteria. DSM-IV criteria for Autistic Disorder or Asperger's Disorder (autism spectrum disorder) will be confirmed by a clinician with expertise with individuals with ASD. Best estimate Diagnosis will be reached using DSM-IV criteria, the Autism Diagnostic Observation Schedule (ADOS-G) and the Autism Diagnostic Interview-Revised (ADI-R).
• Have a Clinical Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Baseline.
• If already receiving stable non-pharmacologic educational, behavioural, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening and will not electively initiate new or modify ongoing interventions for the duration of the study.
• Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigator.

You may not qualify if:

• Patients born prior to 35 weeks gestational age.
• Families without sufficient command of the English Language.
• Patients with any primary psychiatric diagnosis other than autism at Screening.
• Patients with a current neurological disease, including, but not limited to, movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes.
• Pregnant female patients, female patients who are sexually active, female patients using the birth control pill for whatever reason.
• Patients with a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease. Patients with stable epilepsy (no seizures for 6 months) and on stable doses of antiepileptic medications (no changes in 3 months) will be allowed in the study.
• Patients taking psychoactive medication(s).
• Patients taking insulin.
• Patients unable to tolerate venipuncture procedures for blood sampling.
• Patients with parent(s)/caregiver(s) who smoke.
• Patients who have had previous bladder infection(s).
• Patients with a family history of bladder cancer.

Sponsors & Collaborators

• Evdokia Anagnostou: lead
• Holland Bloorview Kids Rehabilitation Hospital: collaborator

Study Sites (1)

Holland Bloorview Kids Rehabilitation Hospital

Toronto, Ontario, M4G 1R8, Canada

Location

Related Publications (1)

• Capano L, Dupuis A, Brian J, Mankad D, Genore L, Hastie Adams R, Smile S, Lui T, Odrobina D, Foster JA, Anagnostou E. A pilot dose finding study of pioglitazone in autistic children. Mol Autism. 2018 Nov 26;9:59. doi: 10.1186/s13229-018-0241-5. eCollection 2018.

  PMID: 30498564 DERIVED

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Evdokia Anagnostou, M.D.

  Holland Bloorview Kids Rehabilitation Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinician Scientist

Study Record Dates

• First Submitted: September 16, 2010
• First Posted: September 20, 2010
• Study Start: April 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: March 20, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)