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

NCT ID: NCT00198107

Last Updated: 2019-04-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2011-09-30

Brief Summary

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

Detailed Description

Autism is a developmental disorder that affects every child differently. A wide range of symptoms accompany autism, including self-injurious behavior, aggression, and severe tantrums. Despite an improved ability to reduce these symptoms, existing drug treatments continue to be associated with adverse side effects. Also, there is no existing drug treatment that reliably improves social behavior, a core deficit in autism. Studies on drug treatment combinations that are designed to reduce self-injurious behavior, aggression, and severe tantrums and improve social behavior in children with autism have yet to be conducted. This study will address the above-mentioned limitations by evaluating aripiprazole in reducing self-injurious behavior, aggression, and severe tantrums and by evaluating the addition of D-Cycloserine in improving social behavior among children with autism.

This study will include three phases and an add-on component for some children. Participants will be randomly assigned to receive either aripiprazole or a placebo treatment for 8 weeks. Assessments measuring irritability, behavior, and social skills will be conducted at the end of this first phase. Those patients who respond well to aripiprazole will continue to receive aripiprazole treatment for another 16 weeks. This second phase will determine whether aripiprazole is associated with long-term maintenance of symptomatic improvement in patients who respond well to short-term treatment. Assessments will again be conducted at the end of this 16-week period. Those patients whose symptoms have stabilized and continue to improve while on aripiprazole will be asked to participate in the final phase of this study. During the this pilot phase, D-Cycloserine will be added to ongoing treatment with aripiprazole. Patients will take both aripiprazole and D-Cycloserine for an additional 8 weeks to determine if this combination of drug treatments results in improved social behavior once patients' aggression and self-injurious behavior have been stabilized with aripiprazole. At the end of this 8-week period, participants will be assessed for any changes in behavior, irritability, or social skills. Results from this study may aid in developing safer and more effective drug treatments for children and adolescents with autism.

Conditions

Autistic Disorder

Study Design

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

Study Groups

1 Placebo

Participants will take placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

2 Aripiprazole

Participants will take aripiprazole

Group Type: ACTIVE_COMPARATOR

Aripiprazole

Intervention Type: 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.

3 Aripiprazole + D-cycloserine

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

Group Type: ACTIVE_COMPARATOR

Aripiprazole

Intervention Type: 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.

D-cycloserine

Intervention Type: DRUG

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

Interventions

Aripiprazole

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

D-cycloserine

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

Intervention Type: DRUG

Other Intervention Names

Abilify

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher J. McDougle, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University School of Medicine

Locations

Riley Hospital for Children, Christian Sarkine Autism Treatment Center

Indianapolis, Indiana, United States

Countries

United States

References

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)

Other Identifiers

R01MH072961

Identifier Type: NIH

Identifier Source: secondary_id

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DSIR 82-SEDR

Identifier Type: -

Identifier Source: secondary_id

R01MH072961

Identifier Type: NIH

Identifier Source: org_study_id

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