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

Purpose

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.

Condition	Intervention	Phase
Autistic Disorder	Drug: Buspirone Drug: Placebo	Phase 2 Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Placebo-controlled, Double-masked Clinical Trial of Buspirone in the Treatment of 2- 6 Year Old Children With Autistic Disorder

Resource links provided by NLM:

MedlinePlus related topics: Anxiety Autism

Drug Information available for: Buspirone hydrochloride Buspirone

U.S. FDA Resources

Further study details as provided by Chugani, Diane C.:

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. [ Time Frame: Baseline 1, Week 24 ] [ Designated as safety issue: No ]

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. [ Time Frame: Baseline 1, Week 24 and Week 48 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
To determine whether the whole brain PET measure of serotonin synthesis capacity is a predictor of buspirone effect. [ Time Frame: Baseline 2 ] [ Designated as safety issue: No ]
To determine whether blood serotonin concentration is a predictor of buspirone effect. [ Time Frame: Baseline 2 ] [ Designated as safety issue: No ]

Estimated Enrollment:	166
Study Start Date:	May 2009
Estimated Study Completion Date:	September 2014
Estimated Primary Completion Date:	September 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Buspirone 2.5 mg	Drug: Buspirone 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
Experimental: 2 Buspirone 5.0 mg	Drug: Buspirone 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
Placebo Comparator: 3 Placebo match	Drug: Placebo 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

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.

Eligibility

Ages Eligible for Study:	2 Years to 6 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00873509

Contacts

Contact: Kristin Kennedy, RN

1-313-745-6615

kkennedy@med.wayne.edu

Locations

United States, California
University California Davis M.I.N.D. Institute	Recruiting
Sacramento, California, United States, 95817
Contact: Erika Bickel 916-703-0281 erika.bickel@ucdmc.ucdavis.edu
Principal Investigator: Robin L Hansen, MD
United States, Michigan
Children's Hospital of Michigan Wayne State University	Active, not recruiting
Detroit, Michigan, United States, 48201
United States, New York
New York University Langone Medical Center	Active, not recruiting
New York, New York, United States, 10016
United States, Ohio
Cleveland Clinic Lerner College of Medicine	Active, not recruiting
Cleveland, Ohio, United States, 44195
Rainbow Babies and Children's Hospital	Active, not recruiting
Cleveland, Ohio, United States, 44106
United States, Texas
University of Texas Southwestern	Active, not recruiting
Dallas, Texas, United States, 75390

Sponsors and Collaborators

Chugani, Diane C.

Investigators

Principal Investigator:

Diane C Chugani, PhD

Wayne State University

More Information

No publications provided

Responsible Party:	Diane C Chugani, Chief, Division of Clinical Pharmacology and Toxicology, Wayne State University
ClinicalTrials.gov Identifier:	NCT00873509 History of Changes
Other Study ID Numbers:	10888, 5-U01-NS061264
Study First Received:	March 30, 2009
Last Updated:	February 25, 2013
Health Authority:	United States: Food and Drug Administration United States: NINDS Data Safety Monitoring Board

Keywords provided by Chugani, Diane C.:

Autism

Additional relevant MeSH terms:

Autistic Disorder
Buspirone
Child Development Disorders, Pervasive
Mental Disorders Diagnosed in Childhood
Mental Disorders
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on June 18, 2013

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