Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00251303
First received: November 9, 2005
Last updated: September 18, 2012
Last verified: September 2012
  Purpose

This study will examine the effectiveness of riluzole for treating Obsessive-Compulsive Disorder in Youth, Including those with Autism Spectrum Disorders.


Condition Intervention Phase
Obsessive-Compulsive Disorder
Autism Spectrum Disorder
Autism
Asperger Disorder
Development Disorder
Drug: Riluzole
Phase 2

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: An Investigation of the Efficacy in Childhood Obsessive-Compulsive Disorder of Riluzole: An Antiglutamatergic Agent

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Reduction of 30% or more in Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) and Repetitive Behavior Scale [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Much/Very much improved on Clinical Global Impressions - Improvement score (CGI-I) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 78
Study Start Date: August 2005
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Riluzole
    N/A
Detailed Description:

Obsessive-Compulsive Disorder (OCD) is a chronic psychiatric disorder characterized by the presence of intrusive and unwanted obsessional thoughts and images and of compulsive behaviors. Its presentation during childhood is similar to that seen in adulthood, except that children sometimes lack insight into the senselessness of the thoughts and behaviors. Although many patients benefit from treatment with selective serotonin reuptake inhibitors (SSRIs), a significant proportion have limited or no response to these medications. Additionally, these medicines have been associated with a slight but significant increase in onset of suicidal thoughts among adolescents being treated for depression or OCD. Cognitive behavioral therapy (CBT) may also be effective for OCD, alone or in combination with SSRIs, but there is a shortage of qualified therapists, and many patients and families cannot participate effectively in the therapy. Further, in a recent report on a multi-site study of childhood OCD, CBT alone at one site fared little better than placebo.

There is a pressing need, then, for the development of alternative, novel treatments for pediatric OCD. Neuropsychological and neuroimaging data suggest that OCD may arise from dysfunction of orbitofronto-striato-thalamocortical circuitry. Glutamate plays a crucial role in the regulation of excitatory activity within this circuit and may be involved in the etiopathogenesis of OCD. If so, then agents which reduce glutamatergic neurotransmission may provide unique antiobsessional benefits. Riluzole is a medication that reduces glutamatergic activity. It is currently being studied in adults with OCD, and this two-stage study will evaluate the possibility that riluzole will help children with OCD, Riluzole has been approved by the Food and Drug Administration (FDA) for treatment of amyotrophic lateral sclerosis (ALS), and is currently under investigation at the NIMH for treatment of depression.

The first stage of this investigation has been completed. Six children with OCD, ages 7 to 17 years, received riluzole as part of a study that evaluated the drug's safety and estimated the appropriate dose of riluzole Riluzole was added to the children's current medication regimen or was used as sole agent. The second stage of the investigation will enroll up to 60 additional subjects with OCD including some who have both autistic spectrum disorder (ASD) and OCD. The subjects will participate in a double-blind, placebo-controlled12-week trial of riluzole as a sole agent or as an augmentation to their currently inadequate therapy. Following the double-blind portion of the trial, subjects may receive three months of open-label treatment with riluzole, if it is clinically indicated. All subjects will be followed at regular intervals until one year from baseline.

  Eligibility

Ages Eligible for Study:   7 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Subjects may be included in the study only if they meet all of the following criteria:

  1. Male or female subjects, 7 to 17 years of age.
  2. Male and female subjects of childbearing potential must be using a medically accepted means of contraception or must remain abstinent.
  3. Each legal guardian must have a level of understanding sufficient to agree to all required tests and examinations. Each legal guardian must understand the nature of the study. Each legal guardian must consent to study protocol.
  4. Subjects must fulfill DSM-IV criteria for (OCD) and have a CY-BOCS score of greater than 20. In the double-blind phase, subjects enrolled in the combined OCD and ASD cohort must also meet DSM-IV criteria for Pervasive Developmental Disorder as well as OCD.
  5. Each subject already taking medicine must be taking usually effective doses of a medicine demonstrated to be effective in childhood OCD, must have been stable on that dose for at least six weeks, and must have no newly recognized or intolerable adverse effects from that medicine. Subjects who are currently not taking such a medication must have had adequate trial in the past of at least one medicine that has been shown to be effective for the symptoms of childhood OCD, and must have failed to see improvement or must have had intolerable adverse effects from the medicine.
  6. Subjects must be able to swallow capsules.

EXCLUSION CRITERIA:

Subjects will be excluded from the study for any of the following reasons:

  1. Presence of psychotic symptoms or lifetime history of schizophrenia, bipolar disorder, other psychotic disorder, or other serious unstable psychiatric illness. Medically unstable due to binging, purging, or starvation.
  2. Judged clinically to be at risk for suicide (suicidal ideation, severe depression, or other factors). Diagnosis of DSM-IV Major Depressive Disorder is not necessarily an exclusion criterion.
  3. Disabling Tic Disorder requiring contraindicated medicines.
  4. Male or female subjects who are unwilling to use effective contraception, or female subjects who are pregnant or nursing.
  5. Serious unstable illnesses, including gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
  6. Renal or hepatic dysfunction that would interfere with excretion or metabolism of riluzole as evidenced by increase above upper limits of normal for BUN/creatinine, or more than two-fold elevation above upper limits of normal of serum transaminases (ALT/SGPT, AST/SGOT), gamma glutamate (GGT), or bilirubin.
  7. Documented history of hypersensitivity or intolerance to riluzole.
  8. DSM-IV Substance Abuse Disorder within the past 90 days or Substance Dependence Disorder within the past 5 years, or any use of tobacco.
  9. Taking contraindicated drugs.
  10. Unable to swallow capsules.
  11. In addition, patients will not receive cognitive-behavior therapy during the period of the study.
  12. Abnormal EEG unless evaluated by a neurologist and approved by that specialist for this protocol.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00251303

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Jennifer A Cameron, Ph.D. National Institute of Mental Health (NIMH)
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Susan E. Swedo, M.D./National Institute of Mental Health, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00251303     History of Changes
Other Study ID Numbers: 050225, 05-M-0225
Study First Received: November 9, 2005
Last Updated: September 18, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Clinical Trial
Glutamate Antagonist
Pediatrics
Basal Ganglia
Neurophyschological
Obsessive Compulsive Disorder
OCD
Riluzole
Rilutek

Additional relevant MeSH terms:
Autistic Disorder
Obsessive-Compulsive Disorder
Asperger Syndrome
Child Development Disorders, Pervasive
Compulsive Personality Disorder
Mental Disorders Diagnosed in Childhood
Mental Disorders
Anxiety Disorders
Personality Disorders
Riluzole
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants

ClinicalTrials.gov processed this record on April 14, 2014