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

Autism Spectrum Disorders Clinical Trial

Official title:

A Pilot Dose Finding Study of Pioglitazone in Children With ASD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01205282
• Other study ID #: 10-002
• Status: Completed
• Phase: Phase 2
• First received: September 16, 2010
• Last updated: March 17, 2017
• Start date: April 2013
• Est. completion date: September 2015

Study information

• Verified date: March 2017
• Source: Anagnostou, Evdokia, M.D.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 12 Years

Eligibility

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.

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autism Spectrum Disorders
• Child Development Disorders, Pervasive

Intervention

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

Locations

Country	Name	City	State
Canada	Holland Bloorview Kids Rehabilitation Hospital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Evdokia Anagnostou	Holland Bloorview Kids Rehabilitation Hospital

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Maximum tolerated dose to be used in the follow-up multisite randomized controlled trial	Maximum Tolerated Dose (MTD)	16 Weeks
Secondary	Efficacy of pioglitazone on markers of inflammation (cytokine levels) and oxidative stress (superoxide dismutase, malonyl aldehydes)	Cytokine level and oxidative stress marker measurement	16 Weeks
Secondary	Relationship between different doses and response to treatment	Pioglitazone dose and treatment response	16 Weeks