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Buspirone in the Treatment of 2-6 Year Old Children With Autistic Disorder (B-ACE)

Primary Purpose

Autistic Disorder

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Buspirone

Placebo

About this trial

This is an interventional treatment trial for Autistic Disorder focused on measuring Autism

Eligibility Criteria

2 Years - 6 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participants: must meet the study definition for diagnosis of autistic disorder as determined by clinical diagnosis based upon DSM-IV criteria, the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) performed at baseline 1. ADI-R will be conducted by trained study staff at Baseline 1 Visit. If the participant has had an ADI-R in the past 12 months, this will be accepted provided the person administering and scoring the test is site personnel validated for the study.
Age 2 to less than 6 years, male and female.
Parent/Legal Guardian/Caregiver must be able to understand , read and speak English
Written Informed Consent.

Exclusion Criteria:

Presence or history of neurological disorders, including seizure disorders (abnormal EEG without seizures will not be excluded), PKU, tuberous sclerosis, Rett syndrome, Fragile X syndrome, Down Syndrome and traumatic brain injury.
Other medical or behavioral problems requiring medications which are centrally active.
Clinical or laboratory evidence of renal or hepatic disease (SGPT, GGT > 2 x normal value, and serum creatinine > 1.5 x normal value).

Treatment with any medication known to alter the activity of the CYP3A4 enzyme including ketoconazole, itraconazole, grapefruit juice, erythromycin, clarithromycin, cimetidine, verapamil, diltiazem, rifampin, phenytoin, phenobarbital, or carbamazepine within the previous 2 months and for the duration of the study is prohibited.

Use of centrally acting drugs during the 6 weeks prior or during the study. These drugs include but are not limited to neuroleptics, benzodiazepines, anticonvulsants and antidepressants. Shorter times may be considered depending on the half life of the drug.
Prior treatment for periods longer than two weeks with buspirone or selective serotonin reuptake inhibitors. This includes herbal substances such as St John's Wort which have similar pharmacological actions.
Known allergies to study medication.
Unable to provide the required blood samples.

Sites / Locations

University California Davis M.I.N.D. Institute
Children's Hospital of Michigan Wayne State University
New York University Langone Medical Center
Rainbow Babies and Children's Hospital
Cleveland Clinic Lerner College of Medicine
University of Texas Southwestern

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

Buspirone 2.5 mg

Buspirone 5.0 mg

Placebo match

Outcomes

Primary Outcome Measures

To evaluate the effects of twice-daily oral buspirone on core features of autism in autistic children 2-6 years measuring the change from baseline in ADOS (Autism Diagnostic Observation Schedule) Composite Total scores compared to placebo at 6 months.

Secondary Outcome Measures

To evaluate the effects of twice-daily oral buspirone on the ADOS Composite calibrated severity score, social behavior, repetitive behavior, language, sensory dysfunction and anxiety.

To determine whether there are age group differences in the effects of buspirone on social interaction, repetitive behavior, language, sensory dysfunction and anxiety.

To determine whether there is a difference in the incidence of side effects and long term safety between the buspirone and placebo groups, and between the different dose groups.

To determine whether the whole brain PET measure of serotonin synthesis capacity is a predictor of buspirone effect.

To determine whether blood serotonin concentration is a predictor of buspirone effect.

Full Information

NCT ID

NCT00873509

First Posted

March 30, 2009

Last Updated

July 25, 2016

Sponsor

Chugani, Diane C.

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

1. Study Identification

Unique Protocol Identification Number

NCT00873509

Brief Title

Buspirone in the Treatment of 2-6 Year Old Children With Autistic Disorder

Acronym

B-ACE

Official Title

A Randomized, Placebo-controlled, Double-masked Clinical Trial of Buspirone in the Treatment of 2- 6 Year Old Children With Autistic Disorder

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Completed

Study Start Date

May 2009 (undefined)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chugani, Diane C.

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to evaluate the effects of twice-daily oral buspirone on core features of autism in autistic children aged 2-6 years as measured by the change from baseline in the Autism Diagnostic Observation Schedule (ADOS) Composite Total scores compared to placebo at 6 months.

Detailed Description

This is a multi-center, randomized, placebo-controlled, double-masked study of 166 evaluable participants taking buspirone twice daily for 6 months. Children aged 2-6 years with autism will be randomized to receive one of three treatments: 2.5mg, 5.0mg, or matched placebo. The placebo controlled trial will be followed by an optional follow-up trial to assess the long term safety of buspirone. In addition, a PET scan of serotonin synthesis and plasma serotonin will be measured at baseline to determine whether these measures are predictors of drug response. This trial is aimed at the core features of autism. The outcome measures for efficacy will be examiner and parent ratings on psychological tests and questionnaires. The outcome measure for the primary objective will be the Autism Diagnostic Observation Scale (ADOS) Composite Total score. The behavioral outcomes for the secondary aims are delineated in the study design.

6. Conditions and Keywords

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

Autistic Disorder

Keywords

Autism

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

166 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Buspirone 2.5 mg

Arm Title

Arm Type

Experimental

Arm Description

Buspirone 5.0 mg

Arm Title

Arm Type

Placebo Comparator

Arm Description

Placebo match

Intervention Type

Drug

Intervention Name(s)

Buspirone

Intervention Description

Buspirone liquid, 2.5 mg in 1 ml, once per day in the evening for the first week of administration and thereafter twice a day 12 hours apart for the entire study

Intervention Type

Drug

Intervention Name(s)

Buspirone

Intervention Description

Buspirone liquid, 5.0 mg in 1 ml , once per day in the evening for the first week of administration and thereafter twice a day 12 hours apart for the entire study

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo liquid, in 1 ml, once per day in the evening for the first week of administration and thereafter twice a day 12 hours apart for the entire study

Primary Outcome Measure Information:

Title

Time Frame

Baseline 1, Week 24

Secondary Outcome Measure Information:

Title

To evaluate the effects of twice-daily oral buspirone on the ADOS Composite calibrated severity score, social behavior, repetitive behavior, language, sensory dysfunction and anxiety.

Time Frame

Baseline 1, Week 24 and Week 48

Title

To determine whether there are age group differences in the effects of buspirone on social interaction, repetitive behavior, language, sensory dysfunction and anxiety.

Time Frame

Baseline 1, Week 1, Week 24, Week 48

Title

To determine whether there is a difference in the incidence of side effects and long term safety between the buspirone and placebo groups, and between the different dose groups.

Time Frame

Duration of the study

Title

To determine whether the whole brain PET measure of serotonin synthesis capacity is a predictor of buspirone effect.

Time Frame

Baseline 2

Title

To determine whether blood serotonin concentration is a predictor of buspirone effect.

Time Frame

Baseline 2

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participants: must meet the study definition for diagnosis of autistic disorder as determined by clinical diagnosis based upon DSM-IV criteria, the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) performed at baseline 1. ADI-R will be conducted by trained study staff at Baseline 1 Visit. If the participant has had an ADI-R in the past 12 months, this will be accepted provided the person administering and scoring the test is site personnel validated for the study. Age 2 to less than 6 years, male and female. Parent/Legal Guardian/Caregiver must be able to understand , read and speak English Written Informed Consent. Exclusion Criteria: Presence or history of neurological disorders, including seizure disorders (abnormal EEG without seizures will not be excluded), PKU, tuberous sclerosis, Rett syndrome, Fragile X syndrome, Down Syndrome and traumatic brain injury. Other medical or behavioral problems requiring medications which are centrally active. Clinical or laboratory evidence of renal or hepatic disease (SGPT, GGT > 2 x normal value, and serum creatinine > 1.5 x normal value). Treatment with any medication known to alter the activity of the CYP3A4 enzyme including ketoconazole, itraconazole, grapefruit juice, erythromycin, clarithromycin, cimetidine, verapamil, diltiazem, rifampin, phenytoin, phenobarbital, or carbamazepine within the previous 2 months and for the duration of the study is prohibited. Use of centrally acting drugs during the 6 weeks prior or during the study. These drugs include but are not limited to neuroleptics, benzodiazepines, anticonvulsants and antidepressants. Shorter times may be considered depending on the half life of the drug. Prior treatment for periods longer than two weeks with buspirone or selective serotonin reuptake inhibitors. This includes herbal substances such as St John's Wort which have similar pharmacological actions. Known allergies to study medication. Unable to provide the required blood samples.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Diane C Chugani, PhD

Organizational Affiliation

Wayne State University

Official's Role

Principal Investigator

Facility Information:

Facility Name

University California Davis M.I.N.D. Institute

City

Sacramento

State/Province

California

ZIP/Postal Code

95817

Country

United States

Facility Name

Children's Hospital of Michigan Wayne State University

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

New York University Langone Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

Rainbow Babies and Children's Hospital

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

Facility Name

Cleveland Clinic Lerner College of Medicine

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Facility Name

University of Texas Southwestern

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

26746121

Citation

Chugani DC, Chugani HT, Wiznitzer M, Parikh S, Evans PA, Hansen RL, Nass R, Janisse JJ, Dixon-Thomas P, Behen M, Rothermel R, Parker JS, Kumar A, Muzik O, Edwards DJ, Hirtz D; Autism Center of Excellence Network. Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial. J Pediatr. 2016 Mar;170:45-53.e1-4. doi: 10.1016/j.jpeds.2015.11.033. Epub 2015 Dec 30.

Results Reference

result

Available IPD and Supporting Information:

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

https://ndar.nih.gov

Learn more about this trial

Buspirone in the Treatment of 2-6 Year Old Children With Autistic Disorder

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