Back to results

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

Primary Purpose

Autism Spectrum Disorders

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Pioglitazone

Placebo

About this trial

This is an interventional treatment trial for Autism Spectrum Disorders focused on measuring ASD

Eligibility Criteria

5 Years - 12 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female outpatients 5-12 years of age inclusive (see Note below).
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).
Have a Clinical Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Baseline.
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.
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:

Patients born prior to 35 weeks gestational age.
Families without sufficient command of the English Language.
Patients with any primary psychiatric diagnosis other than autism at Screening.
Patients with a current neurological disease, including, but not limited to, movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes.
Pregnant female patients, female patients who are sexually active, female patients using the birth control pill for whatever reason.
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.
Patients taking psychoactive medication(s).
Patients taking insulin.
Patients unable to tolerate venipuncture procedures for blood sampling.
Patients with parent(s)/caregiver(s) who smoke.
Patients who have had previous bladder infection(s).
Patients with a family history of bladder cancer.

Sites / Locations

Holland Bloorview Kids Rehabilitation Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Pioglitazone

Placebo

Arm Description

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.

Outcomes

Primary Outcome Measures

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)

Safety of pioglitazone in children with ASD ages 5-12 years

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

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

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

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

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

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

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

Maximum Tolerated Dose (MTD)

Secondary Outcome Measures

Efficacy of pioglitazone on markers of inflammation (cytokine levels) and oxidative stress (superoxide dismutase, malonyl aldehydes)

Cytokine level and oxidative stress marker measurement

Relationship between different doses and response to treatment

Pioglitazone dose and treatment response

Full Information

NCT ID

NCT01205282

First Posted

September 16, 2010

Last Updated

March 17, 2017

Sponsor

Evdokia Anagnostou

Collaborators

Holland Bloorview Kids Rehabilitation Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01205282

Brief Title

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

Official Title

A Pilot Dose Finding Study of Pioglitazone in Children With ASD

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

April 2013 (undefined)

Primary Completion Date

September 2015 (Actual)

Study Completion Date

September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Evdokia Anagnostou

Collaborators

Holland Bloorview Kids Rehabilitation Hospital

4. Oversight

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autism Spectrum Disorders

Keywords

ASD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

Participant

Allocation

Non-Randomized

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pioglitazone

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Pioglitazone

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Safety of pioglitazone in children with ASD ages 5-12 years

Description

This will be measured by the Clinical Global Impressions - Improvement Scale - Global (CGI-I-Global)

Time Frame

16 Weeks

Title

Safety of pioglitazone in children with ASD ages 5-12 years

Description

This will be measured by the Safety Monitoring Uniform Report Form (SMURF)

Time Frame

16 Weeks

Title

Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD

Description

This will be measured by the Aberrant Behavior Checklist (ABC)

Time Frame

16 Weeks

Title

Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD

Description

This will be measured the Social Responsiveness Scale (SRS)

Time Frame

16 Weeks

Title

Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD

Description

This will be measured by the the Child Yale-Brown Obsessive-Compulsive Scale (CY-BOCS)

Time Frame

16 Weeks

Title

Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD

Description

This will be measured by the Repetitive Behavior Scale - Revised (RBS-R)

Time Frame

16 Weeks

Title

Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD

Description

This will be measured by the Behavioral Assessment System for Children (BASC-2)

Time Frame

16 Weeks

Title

Efficacy of outcome measure to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD

Description

This will be measured by the Child and Adolescent Symptom Inventory (CASI) - Anxiety Subscale

Time Frame

16 Weeks

Title

Maximum tolerated dose to be used in the follow-up multisite randomized controlled trial

Description

Maximum Tolerated Dose (MTD)

Time Frame

16 Weeks

Secondary Outcome Measure Information:

Title

Efficacy of pioglitazone on markers of inflammation (cytokine levels) and oxidative stress (superoxide dismutase, malonyl aldehydes)

Description

Cytokine level and oxidative stress marker measurement

Time Frame

16 Weeks

Title

Relationship between different doses and response to treatment

Description

Pioglitazone dose and treatment response

Time Frame

16 Weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female outpatients 5-12 years of age inclusive (see Note below). 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). Have a Clinical Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Baseline. 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. 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: Patients born prior to 35 weeks gestational age. Families without sufficient command of the English Language. Patients with any primary psychiatric diagnosis other than autism at Screening. Patients with a current neurological disease, including, but not limited to, movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes. Pregnant female patients, female patients who are sexually active, female patients using the birth control pill for whatever reason. 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. Patients taking psychoactive medication(s). Patients taking insulin. Patients unable to tolerate venipuncture procedures for blood sampling. Patients with parent(s)/caregiver(s) who smoke. Patients who have had previous bladder infection(s). Patients with a family history of bladder cancer.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Evdokia Anagnostou, M.D.

Organizational Affiliation

Holland Bloorview Kids Rehabilitation Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Holland Bloorview Kids Rehabilitation Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M4G 1R8

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

30498564

Citation

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs