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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2010 by National Institute of Mental Health (NIMH).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:
NCT00198107
First received: September 12, 2005
Last updated: August 24, 2010
Last verified: August 2010
  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
Other: fMRI
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Novel Pharmacological Strategies in Autism

Resource links provided by NLM:


Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:
  • Aberrant Behavior Checklist (ABC) Irritability Subscale [ Time Frame: Measured at Week 8 ] [ Designated as safety issue: No ]
  • Clinical Global Impression (CGI) Scale [ Time Frame: Measured at Weeks 8 and 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ABC Subscales [ Time Frame: Measured at Weeks 8 and 16 ] [ Designated as safety issue: No ]
  • Vineland Maladaptive Behavior Subscales [ Time Frame: Measured at Weeks 8 and 16 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Autism Diagnostic Observation Schedule (ADOS) [ Time Frame: Measured at Weeks 8 and 16 ] [ Designated as safety issue: No ]
  • Social Reciprocity Scale (SRS) [ Time Frame: Measured at Weeks 8 and 16 ] [ Designated as safety issue: No ]

Estimated Enrollment: 88
Study Start Date: September 2005
Estimated Study Completion Date: September 2011
Estimated Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
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
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
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.
Add-on Study
To conduct a double-blind, placebo-controlled fMRI study of brain activation and connectivity patterns before and after aripiprazole with 20 subjects who enter the Study A Phase.
Other: fMRI
Subjects will undergo an fMRI and a facial affect processing task.

Detailed Description:

Autism is a developmental disability that affects every child differently. A wide range of symptoms accompany autism, including self-injurious behavior, severe aggression, and irritability. 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, the core deficit in autism. Studies on drug treatment combinations that are designed to reduce self-injurious behavior, aggression, and irritability 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 irritability 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 last phase, D-Cycloserine will be added to the treatment regimen. 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.

Add-study: The Effects of Aripiprazole on Brain Circuitry in Children and Adolescents with Autism

The purpose of this added phase is to conduct a double-blind, placebo-controlled fMRI study of brain activation and connectivity patterns before and after aripiprazole treatment with 20 subjects who enter Study phase A. Children must be able to comply with the fMRI scan and a facial affect processing task. The child must have the ability to lie still during the scanning procedures and to comply with instructions. The aim is to determine the effects of aripiprazole treatment on amygdalar activation in response to a negative facial emotional task vs. a neutral (control) task. We that hypothesize that compared to placebo, aripiprazole treatment will increase amygdalar activation in response to a negative facial emotion task. In addition we hypothesize that increases in amygdalar activation will positively correlate with improvement on behavioral rating scales.

  Eligibility

Ages Eligible for Study:   5 Years to 17 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00198107

Contacts
Contact: Lauren Mathieu- Frasier, MA 317-948-9766 kidpsych@iupui.edu
Contact: Jennifer E. Mullett, RN 317-948-9766 kidpsych@iupui.edu

Locations
United States, Indiana
Riley Hospital for Children, Christian Sarkine Autism Treatment Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Arlene E. Kohn, BA         
Principal Investigator: Christopher J. McDougle, MD         
Sponsors and Collaborators
Investigators
Principal Investigator: Christopher J. McDougle, MD Indiana University School of Medicine
  More Information

No publications provided

Responsible Party: Christopher J. McDougle, MD, Indiana University School of Medicine
ClinicalTrials.gov Identifier: NCT00198107     History of Changes
Other Study ID Numbers: R01 MH072961, DSIR 82-SEDR
Study First Received: September 12, 2005
Last Updated: August 24, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):
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
Mental Disorders Diagnosed in Childhood
Mental Disorders
Cycloserine
Excitatory Amino Acid Agents
Aripiprazole
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Renal Agents
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Psychotropic Drugs

ClinicalTrials.gov processed this record on July 23, 2014