Riluzole Augmentation in Treatment-refractory Obsessive-compulsive Disorder

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00523718
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 107
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obsessive-compulsive Disorder; Ocd	Drug: riluzole; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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

Outcome Measures

Primary Outcome Measures

1. Partial Responders by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) [14 weeks]

   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

1. Average Hamilton Depression Inventory (HAM-D) [14 weeks]

   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.

2. Average Hamilton Anxiety Inventory (HAM-A) [14 weeks]

   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.

3. Clinical Global Impression (CGI) - Severity of Illness Item [14 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale OCD Research Clinic	New Haven	Connecticut	United States	06508

Sponsors and Collaborators

• Yale University
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Christopher J Pittenger, MD, Ph.D., Yale University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

• 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.
• 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. Review.
• 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. Review.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00523718
• Other Study ID Numbers: 0509000614; R34MH083115
• First Posted: Aug 31, 2007
• Last Update Posted: Mar 6, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by Yale University: obsessive-compulsive disorder; OCD; glutamate; riluzole; augmentation; treatment
• Additional relevant MeSH terms: Disease; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Riluzole

Study Results

Participant Flow

Recruitment Details	Subjects with selective serotonin reuptake inhibitor(SSRI)-refractory OCD were recruited through the Yale OCD Research Clinic between November 2006 and December 2012 using print and internet advertisements, community outreach, and physician referrals.
Pre-assignment Detail	Forty subjects with treatment-refractory OCD were consented; 1 dropped out after consent, and one was excluded after it was revealed they were not taking an SSRI. These individuals were not randomized.

Arm/Group Title	Riluzole	Placebo
Arm/Group Description	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 riluzole: 50 mg PO bid, 12 weeks	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. placebo: placebo, 1 capsule PO bid, 12 weeks
Period Title: Overall Study
STARTED	20	18
COMPLETED	17	18
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	Riluzole	Placebo	Total
Arm/Group Description	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 riluzole: 50 mg PO bid, 12 weeks	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. placebo: placebo, 1 capsule PO bid, 12 weeks	Total of all reporting groups
Overall Participants	19	18	37
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.5 (3.2)	36.4 (3.1)	38.52 (13.80)
Sex: Female, Male (Count of Participants)
Female	11 57.9%	9 50%	20 54.1%
Male	8 42.1%	9 50%	17 45.9%
Race/Ethnicity, Customized (participants) [Number]
White	19 100%	16 88.9%	35 94.6%
African American	0 0%	2 11.1%	2 5.4%
Y-BOCS baseline score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	30 (5.12)	30.73 (5.81)	30.37 (5.41)
HDRS baseline score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	12.68 (6.89)	13.05 (6.19)	12.87 (6.46)
HARS baseline score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	16.2 (7.35)	15.95 (6.433)	16.08 (6.80)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Riluzole	Placebo
Arm/Group Description	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 riluzole: 50 mg PO bid, 12 weeks	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. placebo: placebo, 1 capsule PO bid, 12 weeks
Measure Participants	19	18
Number [participants]	5 26.3%	2 11.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Riluzole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.24
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Average Hamilton Depression Inventory (HAM-D)
Description	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.
Time Frame	14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Riluzole	Placebo
Arm/Group Description	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 riluzole: 50 mg PO bid, 12 weeks	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. placebo: placebo, 1 capsule PO bid, 12 weeks
Measure Participants	19	18
Mean (Standard Deviation) [units on a scale]	11.941 (6.91)	12.53 (5.67)

3. Secondary Outcome

Title	Average Hamilton Anxiety Inventory (HAM-A)
Description	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.
Time Frame	14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Riluzole	Placebo
Arm/Group Description	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 riluzole: 50 mg PO bid, 12 weeks	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. placebo: placebo, 1 capsule PO bid, 12 weeks
Measure Participants	19	18
Mean (Standard Deviation) [units on a scale]	14.176 (6.80)	14.263 (6.19)

4. Secondary Outcome

Title	Clinical Global Impression (CGI) - Severity of Illness Item
Description	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.
Time Frame	14 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Riluzole	Placebo
Arm/Group Description	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 riluzole: 50 mg PO bid, 12 weeks	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. placebo: placebo, 1 capsule PO bid, 12 weeks
Measure Participants	19	18
Mean (Standard Deviation) [units on a scale]	3.94 (1.09)	3.95 (1.026)

Adverse Events

Adverse Event Reporting Description	Physical side effects were assessed by the Physical Symptom Checklist. Data from the Physical Symptom Checklist were not available for the first 4 patients randomized; the n for this analysis is therefore 16 for riluzole and 17 for placebo.
Arm/Group Title	Riluzole		Placebo
Arm/Group Description	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 riluzole: 50 mg PO bid, 12 weeks		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. placebo: placebo, 1 capsule PO bid, 12 weeks
All Cause Mortality
	Riluzole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Riluzole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/19 (5.3%)		1/18 (5.6%)
Psychiatric disorders
Passively Suicidal	1/19 (5.3%)	1	0/18 (0%)	0
Overdose of Narcotics	0/19 (0%)	0	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Riluzole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/16 (43.8%)		11/17 (64.7%)
Cardiac disorders
Pounding Heart Beat	0/16 (0%)		3/17 (17.6%)
Gastrointestinal disorders
Nausea	3/16 (18.8%)		1/17 (5.9%)
Constipation	1/16 (6.3%)		6/17 (35.3%)
Nervous system disorders
Poor Coordination	3/16 (18.8%)		1/17 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.