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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00198107
First Posted: September 20, 2005
Last Update Posted: April 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Indiana University
  Purpose
This study will determine the effectiveness of aripiprazole and D-Cycloserine in treating symptoms associated with autism in children.

Condition Intervention Phase
Autistic Disorder Drug: Aripiprazole Drug: Placebo Drug: D-cycloserine Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Novel Pharmacological Strategies in Autism

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Aberrant Behavior Checklist (ABC) Irritability Subscale [ Time Frame: Measured at Week 8 ]
  • Clinical Global Impression (CGI) Scale [ Time Frame: Measured at Weeks 8 and 16 ]

Secondary Outcome Measures:
  • ABC Subscales [ Time Frame: Measured at Weeks 8 and 16 ]
  • Vineland Maladaptive Behavior Subscales [ Time Frame: Measured at Weeks 8 and 16 ]
  • A modified version of the Compulsion Subscale of the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) [ Time Frame: Measured at Weeks 8 and 16 ]
  • Autism Diagnostic Observation Schedule (ADOS) [ Time Frame: Measured at Weeks 8 and 16 ]
  • Social Reciprocity Scale (SRS) [ Time Frame: Measured at Weeks 8 and 16 ]

Enrollment: 81
Study Start Date: September 2005
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1 Placebo
Participants will take placebo
Drug: Placebo
Participants assigned to placebo will take a placebo pill for the initial 8 weeks of treatment.
Active Comparator: 2 Aripiprazole
Participants will take aripiprazole
Drug: 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 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.
Other Name: Abilify
Active Comparator: 3 Aripiprazole + D-cycloserine
Participants first will take aripiprazole then will also take D-cycloserine
Drug: 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 mg maximum dose will be 10 mg per day. Dosing schedule for participants greater than 50 kg maximum dose will be 15 mg.
Other Name: Abilify
Drug: D-cycloserine
D-cycloserine will be dosed in the range of 25 to 200 mg daily for the final 8 weeks of treatment.

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00198107


Locations
United States, Indiana
Riley Hospital for Children, Christian Sarkine Autism Treatment Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Christopher J. McDougle, MD Indiana University School of Medicine
  More Information

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00198107     History of Changes
Other Study ID Numbers: R01MH072961 ( U.S. NIH Grant/Contract )
DSIR 82-SEDR
First Submitted: September 12, 2005
First Posted: September 20, 2005
Last Update Posted: April 20, 2017
Last Verified: April 2017

Keywords provided by Indiana University:
Children
Adolescents
Aripiprazole
Cycloserine
Aggression
Irritability
Self-Injurious Behavior
Social Interaction
Antipsychotics
Pharmacology
Glutamatergic Agents

Additional relevant MeSH terms:
Autistic Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Aripiprazole
Cycloserine
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action