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

Autistic Disorder Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00873509
• Other study ID #: 10888
• Secondary ID: 5U01NS061264
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: March 30, 2009
• Last updated: July 25, 2016
• Start date: May 2009
• Est. completion date: January 2015

Study information

• Verified date: July 2016
• Source: Chugani, Diane C.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: NINDS Data Safety Monitoring Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 166
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 6 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Autistic Disorder
• Disease

Intervention

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
• 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
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

Locations

Country	Name	City	State
United States	Cleveland Clinic Lerner College of Medicine	Cleveland	Ohio
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Children's Hospital of Michigan Wayne State University	Detroit	Michigan
United States	New York University Langone Medical Center	New York	New York
United States	University California Davis M.I.N.D. Institute	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
Chugani, Diane C.	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Restric — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Baseline 1, Week 24	No
Secondary	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.		Baseline 1, Week 24 and Week 48	No
Secondary	To determine whether there are age group differences in the effects of buspirone on social interaction, repetitive behavior, language, sensory dysfunction and anxiety.		Baseline 1, Week 1, Week 24, Week 48	No
Secondary	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.		Duration of the study	Yes
Secondary	To determine whether the whole brain PET measure of serotonin synthesis capacity is a predictor of buspirone effect.		Baseline 2	No
Secondary	To determine whether blood serotonin concentration is a predictor of buspirone effect.		Baseline 2	No