Dose Finding Study of Pioglitazone in Children With Autism Spectrum Disorders (ASD) (PIO)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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.
|
Outcome Measures
Primary Outcome Measures
- Safety of pioglitazone in children with ASD ages 5-12 years [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 [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 [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 [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 [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 [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 [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 [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 [16 Weeks]
Maximum Tolerated Dose (MTD)
Secondary Outcome Measures
- Efficacy of pioglitazone on markers of inflammation (cytokine levels) and oxidative stress (superoxide dismutase, malonyl aldehydes) [16 Weeks]
Cytokine level and oxidative stress marker measurement
- Relationship between different doses and response to treatment [16 Weeks]
Pioglitazone dose and treatment response
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female outpatients 5-12 years of age inclusive (see Note below).
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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).
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Have a Clinical Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Baseline.
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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.
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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:
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Patients born prior to 35 weeks gestational age.
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Families without sufficient command of the English Language.
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Patients with any primary psychiatric diagnosis other than autism at Screening.
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Patients with a current neurological disease, including, but not limited to, movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes.
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Pregnant female patients, female patients who are sexually active, female patients using the birth control pill for whatever reason.
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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.
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Patients taking psychoactive medication(s).
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Patients taking insulin.
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Patients unable to tolerate venipuncture procedures for blood sampling.
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Patients with parent(s)/caregiver(s) who smoke.
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Patients who have had previous bladder infection(s).
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Patients with a family history of bladder cancer.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 10-002