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
  Purpose
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.

Condition Intervention Phase
Autism Spectrum Disorders
Drug: Pioglitazone
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Pilot Dose Finding Study of Pioglitazone in Children With ASD

Resource links provided by NLM:


Further study details as provided by Anagnostou, Evdokia, M.D.:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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


Enrollment: 28
Study Start Date: April 2013
Study Completion Date: September 2015
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Placebo Comparator: Placebo Drug: Placebo
There will be a 2 week period of placebo run-in.

  Eligibility

Ages Eligible for Study:   5 Years to 12 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01205282

Locations
Canada, Ontario
Holland Bloorview Kids Rehabilitation Hospital
Toronto, Ontario, Canada, M4G 1R8
Sponsors and Collaborators
Evdokia Anagnostou
Holland Bloorview Kids Rehabilitation Hospital
Investigators
Principal Investigator: Evdokia Anagnostou, M.D. Holland Bloorview Kids Rehabilitation Hospital
  More Information

Responsible Party: Evdokia Anagnostou, Clinician Scientist, Anagnostou, Evdokia, M.D.
ClinicalTrials.gov Identifier: NCT01205282     History of Changes
Other Study ID Numbers: 10-002 
Study First Received: September 16, 2010
Last Updated: April 12, 2016
Health Authority: Canada: Health Canada
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Anagnostou, Evdokia, M.D.:
ASD

Additional relevant MeSH terms:
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 24, 2016