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

NCT ID: NCT00873509

Last Updated: 2016-07-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 166 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2015-01-31

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.

Conditions

Autistic Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Buspirone 2.5 mg

Group Type: EXPERIMENTAL

Buspirone

Intervention Type: DRUG

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

2

Buspirone 5.0 mg

Group Type: EXPERIMENTAL

Buspirone

Intervention Type: DRUG

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

3

Placebo match

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Chugani, Diane C.

INDIV

Sponsor Role: lead

Responsible Party

Diane C Chugani

Chief, Division of Clinical Pharmacology and Toxicology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Diane C Chugani, PhD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Locations

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

Sacramento, California, 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

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Cleveland Clinic Lerner College of Medicine

Cleveland, Ohio, United States

University of Texas Southwestern

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 26746121 (View on PubMed)

Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

Reference Type: DERIVED

PMID: 37811711 (View on PubMed)

Study Documents

Document Type: Individual Participant Data Set

View Document

Other Identifiers

5U01NS061264

Identifier Type: NIH

Identifier Source: secondary_id

View Link

10888

Identifier Type: -

Identifier Source: org_study_id