Clinical trial NCT00523718: Riluzole Augmentation in Treatment-refractory Obsessive-compulsive Disorder
Official title: A Double-blind Study of Riluzole Augmentation in Serotonin Reuptake Inhibitor-refractory Obsessive-compulsive Disorder and Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obsessive-compulsive Disorder
Ocd
Keywords: obsessive-compulsive disorder
OCD
glutamate
riluzole
augmentation
treatment
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2007-08-31
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Partial Responders by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)
timeFrame: 14 weeks
Secondary outcomes:
measure: Average Hamilton Depression Inventory (HAM-D)
timeFrame: 14 weeks
measure: Average Hamilton Anxiety Inventory (HAM-A)
timeFrame: 14 weeks
measure: Clinical Global Impression (CGI) - Severity of Illness Item
timeFrame: 14 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale OCD Research Clinic
state: Connecticut
Study officials:
affiliation: Yale University
name: Christopher J Pittenger, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.