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

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ClinicalTrials.gov Identifier: NCT01205282
Recruitment Status : Completed
First Posted : September 20, 2010
Last Update Posted : March 20, 2017
Sponsor:
Collaborator:
Holland Bloorview Kids Rehabilitation Hospital
Information provided by (Responsible Party):
Evdokia Anagnostou, Anagnostou, Evdokia, M.D.

Tracking Information
First Submitted Date  ICMJE September 16, 2010
First Posted Date  ICMJE September 20, 2010
Last Update Posted Date March 20, 2017
Study Start Date  ICMJE April 2013
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 9, 2016)
  • Safety of pioglitazone in children with ASD ages 5-12 years [ Time Frame: 16 Weeks ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    Maximum Tolerated Dose (MTD)
Original Primary Outcome Measures  ICMJE
 (submitted: September 17, 2010)
Clinical Global Impression - Improvement (CGI-I) [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2016)
  • Efficacy of pioglitazone on markers of inflammation (cytokine levels) and oxidative stress (superoxide dismutase, malonyl aldehydes) [ Time Frame: 16 Weeks ]
    Cytokine level and oxidative stress marker measurement
  • Relationship between different doses and response to treatment [ Time Frame: 16 Weeks ]
    Pioglitazone dose and treatment response
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Finding Study of Pioglitazone in Children With Autism Spectrum Disorders (ASD) (PIO)
Official Title  ICMJE A Pilot Dose Finding Study of Pioglitazone in Children With ASD
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Autism Spectrum Disorders
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 12, 2016)
28
Original Estimated Enrollment  ICMJE
 (submitted: September 17, 2010)
35
Actual Study Completion Date  ICMJE September 2015
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years to 12 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01205282
Other Study ID Numbers  ICMJE 10-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Evdokia Anagnostou, Anagnostou, Evdokia, M.D.
Study Sponsor  ICMJE Evdokia Anagnostou
Collaborators  ICMJE Holland Bloorview Kids Rehabilitation Hospital
Investigators  ICMJE
Principal Investigator: Evdokia Anagnostou, M.D. Holland Bloorview Kids Rehabilitation Hospital
PRS Account Anagnostou, Evdokia, M.D.
Verification Date March 2017

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