Riluzole Augmentation in Treatment-refractory Obsessive-compulsive Disorder

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
A Double-blind Study of Riluzole Augmentation in Serotonin Reuptake Inhibitor-refractory Obsessive-compulsive Disorder and Depression

Conditions
-----------------
Obsessive-compulsive Disorder, Ocd

Intervention / Treatment
-----------------
* Drug: riluzole
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) diagnosis of OCD, confirmed by Structured Clinical Interview for DSM-IV (SCID-IV); symptoms of at least 1 year duration moderate to severe OCD symptoms as measured by a score on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of 16 or greater documented failure of an adequate trial of a selective serotonin reuptake inhibitor (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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: riluzole<br>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<br>* 50 mg PO bid, 12 weeks<br>* Other names: Rilutek (Sanofi-Aventis);|
| Placebo Comparator: placebo<br>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<br>* placebo, 1 capsule PO bid, 12 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial Responders by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) | 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 | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Hamilton Depression Inventory (HAM-D) | The HDRS (also known as the HAM-D) is the most widely used clinician-administered depression assessment scale. The HAM-D 17-item scale ranges from 0 (normal) to >23 (very severe depression), with a maximum score of 52. The 24-item scale has a maximum score of 75. Severity of depression (e.g. normal or very severe) is based upon the score in the first 17-items. | 14 weeks | 
| Average Hamilton Anxiety Inventory (HAM-A) | 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. A score of 25 to 30 indicates a moderate to severe anxiety severity. A score of 31 or greater represents very severe anxiety severity. | 14 weeks | 
| Clinical Global Impression (CGI) - Severity of Illness Item | 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. | 14 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
obsessive-compulsive disorder, OCD, glutamate, riluzole, augmentation, treatment