Riluzole Augmentation in Treatment-refractory Obsessive-compulsive Disorder

NCT00523718 | Completed Phase 2 Results

• 2 other identifiers: 0509000614R34MH083115
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Obsessive-compulsive Disorder; Ocd

Keywords

obsessive-compulsive disorder; OCD; glutamate; riluzole; augmentation; treatment

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Average Hamilton Depression Inventory (HAM-D)

  14 weeks

• Average Hamilton Anxiety Inventory (HAM-A)

  14 weeks

• Clinical Global Impression (CGI) - Severity of Illness Item

  14 weeks

Study Arms (2)

riluzole

EXPERIMENTAL

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

placebo

PLACEBO COMPARATOR

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

Interventions

riluzole DRUG

50 mg PO bid, 12 weeks

Also known as: Rilutek (Sanofi-Aventis)

riluzole

placebo DRUG

placebo, 1 capsule PO bid, 12 weeks

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Yale OCD Research Clinic

New Haven, Connecticut, 06508, United States

Location

Related Publications (4)

• Pittenger C, Krystal JH, Coric V. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder. NeuroRx. 2006 Jan;3(1):69-81. doi: 10.1016/j.nurx.2005.12.006.

  PMID: 16490414 BACKGROUND

• Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, Saksa J, Wu YT, Gueorguieva R, Sanacora G, Malison RT, Krystal JH. Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005 Sep 1;58(5):424-8. doi: 10.1016/j.biopsych.2005.04.043.

  PMID: 15993857 BACKGROUND

• Pittenger C, Bloch MH, Williams K. Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment. Pharmacol Ther. 2011 Dec;132(3):314-32. doi: 10.1016/j.pharmthera.2011.09.006. Epub 2011 Sep 22.

  PMID: 21963369 BACKGROUND

• Pittenger C, Bloch MH, Wasylink S, Billingslea E, Simpson R, Jakubovski E, Kelmendi B, Sanacora G, Coric V. Riluzole augmentation in treatment-refractory obsessive-compulsive disorder: a pilot randomized placebo-controlled trial. J Clin Psychiatry. 2015 Aug;76(8):1075-84. doi: 10.4088/JCP.14m09123.

  PMID: 26214725 DERIVED

Related Links

• Yale OCD Research Clinic website
• new Yale OCD Research Clinic website

MeSH Terms

Conditions

Obsessive-Compulsive Disorder; Compulsive Personality Disorder

Interventions

Riluzole

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders; Personality Disorders

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Christopher Pittenger
• Organization: Yale University

christopher.pittenger@yale.edu

(203) 974-7675

Study Officials

• Christopher J Pittenger, MD, Ph.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2007
• First Posted: August 31, 2007
• Study Start: September 1, 2006
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: March 6, 2020
• Results First Posted: March 23, 2016

Record last verified: 2020-03

Locations

US (1)