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

This study has been completed.
Sponsor:
Collaborator:
Holland Bloorview Kids Rehabilitation Hospital
Information provided by (Responsible Party):
Evdokia Anagnostou, Anagnostou, Evdokia, M.D.
ClinicalTrials.gov Identifier:
NCT01205282
First received: September 16, 2010
Last updated: April 12, 2016
Last verified: April 2016

September 16, 2010
April 12, 2016
April 2013
September 2015   (final data collection date for primary outcome measure)
  • Safety of pioglitazone in children with ASD ages 5-12 years [ Time Frame: 16 Weeks ] [ Designated as safety issue: Yes ]
    This will be measured by the Clinical Global Impressions - Improvement Scale - Global (CGI-I-Global)
  • Safety of pioglitazone in children with ASD ages 5-12 years [ Time Frame: 16 Weeks ] [ Designated as safety issue: Yes ]
    This will be measured by the Safety Monitoring Uniform Report Form (SMURF)
  • Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    This will be measured by the Aberrant Behavior Checklist (ABC)
  • Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    This will be measured the Social Responsiveness Scale (SRS)
  • Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    This will be measured by the the Child Yale-Brown Obsessive-Compulsive Scale (CY-BOCS)
  • Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    This will be measured by the Repetitive Behavior Scale - Revised (RBS-R)
  • Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    This will be measured by the Behavioral Assessment System for Children (BASC-2)
  • Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    This will be measured by the Child and Adolescent Symptom Inventory (CASI) - Anxiety Subscale
  • Maximum tolerated dose to be used in the follow-up multisite randomized controlled trial [ Time Frame: 16 Weeks ] [ Designated as safety issue: Yes ]
    Maximum Tolerated Dose (MTD)
Clinical Global Impression - Improvement (CGI-I) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01205282 on ClinicalTrials.gov Archive Site
  • Efficacy of pioglitazone on markers of inflammation (cytokine levels) and oxidative stress (superoxide dismutase, malonyl aldehydes) [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    Cytokine level and oxidative stress marker measurement
  • Relationship between different doses and response to treatment [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    Pioglitazone dose and treatment response
Not Provided
Not Provided
Not Provided
 
Dose Finding Study of Pioglitazone in Children With Autism Spectrum Disorders (ASD) (PIO)
A Pilot Dose Finding Study of Pioglitazone in Children With ASD
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.
Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Autism Spectrum Disorders
  • Drug: Pioglitazone
    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.
  • Drug: Placebo
    There will be a 2 week period of placebo run-in.
  • Experimental: Pioglitazone
    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.
    Intervention: Drug: Pioglitazone
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
28
September 2015
September 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Male or female outpatients 5-12 years of age inclusive (see Note below).
  2. 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).
  3. Have a Clinical Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Baseline.
  4. 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.
  5. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigator.

Exclusion Criteria:

  1. Patients born prior to 35 weeks gestational age.
  2. Families without sufficient command of the English Language.
  3. Patients with any primary psychiatric diagnosis other than autism at Screening.
  4. Patients with a current neurological disease, including, but not limited to, movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes.
  5. Pregnant female patients, female patients who are sexually active, female patients using the birth control pill for whatever reason.
  6. 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.
  7. Patients taking psychoactive medication(s).
  8. Patients taking insulin.
  9. Patients unable to tolerate venipuncture procedures for blood sampling.
  10. Patients with parent(s)/caregiver(s) who smoke.
  11. Patients who have had previous bladder infection(s).
  12. Patients with a family history of bladder cancer.
Both
5 Years to 12 Years
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01205282
10-002
No
No
Not Provided
Evdokia Anagnostou, Anagnostou, Evdokia, M.D.
Evdokia Anagnostou
Holland Bloorview Kids Rehabilitation Hospital
Principal Investigator: Evdokia Anagnostou, M.D. Holland Bloorview Kids Rehabilitation Hospital
Anagnostou, Evdokia, M.D.
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP