Riluzole Augmentation in Treatment-refractory Obsessive-compulsive Disorder

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT00523718
First received: August 29, 2007
Last updated: February 22, 2016
Last verified: February 2016
  Purpose

Obsessive-compulsive disorder (OCD) affects 2-3% of the population and leads to a great deal of suffering. Many patients benefit from established treatments, the mainstay of which are cognitive behavioral therapy and a group of antidepressant medications known as serotonin reuptake inhibitors. However, 20-30% of patients get minimal benefit from these established therapeutic strategies. New avenues of treatment are urgently needed.

Existing medications for obsessive-compulsive disorder affect the neurotransmitters serotonin or dopamine; but increasing evidence suggests that functional disruptions of a different neurotransmitter, glutamate, may contribute to some cases of OCD. The investigators are therefore interested in using medications that target glutamate as novel treatment options for those OCD patients who do not benefit from established treatments.

One such medication is the drug riluzole, which is FDA approved for amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, but may be of benefit to patients with psychiatric disorders due to its ability to moderate excessive glutamate. In preliminary studies, in which the investigators treated patients with riluzole (in addition to their established pharmacological regimen) in an open-label fashion (that is, without a placebo-treated control group), the investigators have found about 40-50% of patients to substantially improve over 2-3 months.

While immensely promising, these preliminary studies do not prove riluzole is truly a new beneficial medication for the treatment of OCD; a more rigorous placebo-controlled trial is needed for that purpose. The investigators are therefore now recruiting patients to participate in a double-blind, placebo-controlled trial of riluzole, added to whatever other OCD medications they are taking.


Condition Intervention Phase
Obsessive-compulsive Disorder
Ocd
Drug: riluzole
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind Study of Riluzole Augmentation in Serotonin Reuptake Inhibitor-refractory Obsessive-compulsive Disorder and Depression

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Partial Responders by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]

    The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is a test to rate the severity of obsessive-compulsive disorder (OCD) symptoms. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms), yielding a total possible score range from 0 to 40. The results can be interpreted based on the total score:

    0-7 is sub-clinical; 8-15 is mild; 16-23 is moderate; 24-31 is severe; 32-40 is extreme.

    Improvement was defined apriori as a 25% improvement from baseline



Secondary Outcome Measures:
  • Average Hamilton Depression Inventory (HAM-D) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The HDRS (also known as the Ham-D) is the most widely used clinician-administered depression assessment scale.The HAM-D ranges from 0 (Normal) to >23 (Very Severe Depression).

  • Average Hamilton Anxiety Inventory (HAM-A) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The Hamilton Anxiety Rating Scale (HARS or HAM-A) is a psychological questionnaire used by clinicians to rate the severity of a patient's anxiety. Total score ranges from 0 to 56. A score of 17 or less indicates mild anxiety severity. A score from 18 to 24 indicates mild to moderate anxiety severity. Lastly, a score of 25 to 30 indicates a moderate to severe anxiety severity.

  • Clinical Global Impression (CGI) - Severity of Illness Item [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.


Enrollment: 40
Study Start Date: September 2006
Study Completion Date: August 2015
Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: riluzole
Patients randomized to this arm will receive riluzole augmentation, at a standard, fixed dose (50 mg bid), in addition to the medication regimen they are on at enrollment
Drug: riluzole
50 mg PO bid, 12 weeks
Other Name: Rilutek (Sanofi-Aventis)
Placebo Comparator: placebo
Patients randomized to this arm will receive placebo, formulated to be indistinguishable from riluzole, in addition to the medication regimen they are on at study enrollment.
Drug: placebo
placebo, 1 capsule PO bid, 12 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • DSM-IV diagnosis of OCD, confirmed by SCID-IV; symptoms of at least 1 year duration
  • moderate to severe OCD symptoms (Y-BOCS > 16)
  • documented failure of an adequate trial of an SSRI
  • agreement to engage in a reliable form of birth control (women only)

Exclusion Criteria:

  • primary diagnosis of a psychotic disorder
  • active substance abuse or dependence
  • unstable medical condition
  • prior exposure to riluzole
  • prior psychosurgery
  • pregnancy, breastfeeding, or intent to become pregnant during study
  • liver function tests (LFTs) elevated to more than 2x the upper limit of normal
  • evidence of active liver disease
  • seizure disorder
  • active suicidal ideation
  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: NCT00523718

Locations
United States, Connecticut
Yale OCD Research Clinic
New Haven, Connecticut, United States, 06508
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Christopher J Pittenger, MD, Ph.D. Yale University
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00523718     History of Changes
Other Study ID Numbers: YOCD-1 
Study First Received: August 29, 2007
Results First Received: February 22, 2016
Last Updated: February 22, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
obsessive-compulsive disorder
OCD
glutamate
riluzole
augmentation
treatment

Additional relevant MeSH terms:
Compulsive Behavior
Compulsive Personality Disorder
Obsessive-Compulsive Disorder
Anxiety Disorders
Impulsive Behavior
Mental Disorders
Personality Disorders
Riluzole
Serotonin Uptake Inhibitors
Anticonvulsants
Central Nervous System Agents
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Serotonin Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 27, 2016