Riluzole Augmentation in Treatment-refractory Obsessive-compulsive Disorder

NCT ID: NCT00523718

Last Updated: 2020-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2015-08-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

riluzole

Intervention Type: DRUG

50 mg PO bid, 12 weeks

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo, 1 capsule PO bid, 12 weeks

Interventions

riluzole

50 mg PO bid, 12 weeks

Intervention Type: DRUG

placebo

placebo, 1 capsule PO bid, 12 weeks

Intervention Type: DRUG

Other Intervention Names

Rilutek (Sanofi-Aventis)

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher J Pittenger, MD, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale OCD Research Clinic

New Haven, Connecticut, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 16490414 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15993857 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21963369 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26214725 (View on PubMed)

Related Links

http://www.ocd.yale.edu

Yale OCD Research Clinic website

Other Identifiers

R34MH083115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0509000614

Identifier Type: -

Identifier Source: org_study_id