Evaluating the Effectiveness of Aripiprazole and D-Cycloserine to Treat Symptoms Associated With Autism

NCT00198107 | Completed Phase 3 Results DMC

• 2 other identifiers: R01MH072961DSIR 82-SEDR
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine the effectiveness of aripiprazole and D-Cycloserine in treating symptoms associated with autism in children.

Conditions

Autistic Disorder

Keywords

Children; Adolescents; Aripiprazole; Cycloserine; Aggression; Irritability; Self-Injurious Behavior; Social Interaction; Antipsychotics; Pharmacology; Glutamatergic Agents

Outcome Measures

Primary Outcomes (2)

• Mean Post-baseline Aberrant Behavior Checklist Irritability Score, Parent Report, Double-blind Phase

  The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials of children with developmental disabilities. The interpretation of the tool and its subscales is that higher scores, indicate greater severity. Fifteen item scores with values ranging from 0 (not a problem) to 3 (problem is severe) are summed to arrive at the total irritability scale store ranging from 0 to 45. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and sex x Tanner stage stratum as covariates. A linear contrast estimated the average across study timepoints. Confidence intervals reflect a Bonferroni multiple testing correction accounting

  Weeks 1, 2, 3, 4, 6, and 8

• Odds of Improvement as Measured by the Clinical Global Impression-Global Improvement Scale (Improvement Defined as CGI-I=1 or CGI-I=2)

  Clinical Global Impressions (Guy, 1976) global improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7, with lower scores indicating greater improvement (1=very much improved and 2=much improved). Participants with a CGI-I score of 1 or 2 were classified as improved. Odds were estimated using a repeated measures logistic regression model with treatment group, study week (in categories), and sex x Tanner stage stratum as covariates. A linear contrast estimated the average log odds across study timepoints. Confidence intervals reflect a Bonferroni multiple testing correction accounting for the selection of two primary outcomes.

  Weeks 1, 2, 3, 4, 6 and 8

Secondary Outcomes (8)

• Mean Post-baseline Aberrant Behavior Checklist Hyperactivity Score, Parent Report, Double-blind Phase

  Weeks 1, 2, 3, 4, 6 and 8

• Mean Post-baseline Aberrant Behavior Checklist Inappropriate Speech Score, Parent Report, Double-blind Phase

  Weeks 1, 2, 3, 4, 6, and 8

• Mean Post-baseline Aberrant Behavior Checklist Social Withdrawal Score, Parent Report, Double-blind Phase

  Weeks 1, 2, 3, 4, 6, and 8

• Mean Post-baseline Aberrant Behavior Checklist Stereotypy Score, Parent Report, Double-blind Phase

  Weeks 1, 2, 3, 4, 6, and 8

• Mean Post-baseline Score on a Modified Version of the Compulsion Subscale of the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)

  Weeks 2, 4, 6 and 8

Study Arms (3)

1 Placebo

PLACEBO COMPARATOR

Participants will take placebo

Drug: Placebo

2 Aripiprazole

ACTIVE COMPARATOR

Participants will take aripiprazole

Drug: Aripiprazole

3 Aripiprazole + D-cycloserine

ACTIVE COMPARATOR

Participants first will take aripiprazole then will also take D-cycloserine

Drug: Aripiprazole; Drug: D-cycloserine

Interventions

Aripiprazole DRUG

Participants will receive 8 weeks of initial treatment with aripiprazole. If responsive to treatment, participants may be assigned to an additional 16 weeks of aripiprazole and then an additional 8 more weeks of aripiprazole with D-cycloserine. Dosing schedule for participants less than 50 kg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.

Also known as: Abilify

2 Aripiprazole; 3 Aripiprazole + D-cycloserine

Placebo DRUG

Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.

1 Placebo

D-cycloserine DRUG

D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

3 Aripiprazole + D-cycloserine

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Weight of at least 15 kg (33.75 lbs)
• Meets DSM-IV criteria for autistic disorder
• Outpatient
• Medication-free for at least 2 weeks prior to baseline for all psychotropic medications. More information about this criterion, including exceptions, can be found in the protocol.
• Clinical Global Impression Scale Severity score (CGI-S) of at least 4
• Irritability subscale of the Aberrant Behavior Checklist (ABC) score of at least 18
• An IQ of at least 35 or a mental age of at least 18 months
• In good physical health

You may not qualify if:

• Meets DSM-IV criteria for Asperger's disorder, Rett's disorder, childhood disintegrative disorder, any other pervasive developmental disorder (PDD), schizophrenia, psychotic disorder, or bipolar disorder
• Current or past history of alcohol or other substance abuse within 6 months of study entry
• Comorbid neurodevelopmental disorder with possible association to autism (e.g., fragile-X syndrome, tuberous sclerosis)
• A significant medical condition such as heart, liver, kidney, or lung disease, or a seizure disorder
• Pregnant
• Prior adequate use of aripiprazole. More information about this criterion can be found in the protocol.
• Evidence of hypersensitivity to aripiprazole
• History of neuroleptic malignant syndrome

Sponsors & Collaborators

• Indiana University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Riley Hospital for Children, Christian Sarkine Autism Treatment Center

Indianapolis, Indiana, 46202, United States

Location

Related Publications (1)

• 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.

  PMID: 37811711 DERIVED

MeSH Terms

Conditions

Autistic Disorder; Aggression; Self-Injurious Behavior

Interventions

Aripiprazole; Cycloserine

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Social Behavior

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Isoxazoles; Azoles; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Christopher J. McDougle, MD
• Organization: Indiana University

cmcdougle@partners.org

781-860-1783

Study Officials

• Christopher J. McDougle, MD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: September 1, 2005
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: April 9, 2019
• Results First Posted: March 29, 2019

Record last verified: 2018-04

Locations

US (1)