Trial Outcomes & Findings for Riluzole Augmentation in Treatment-refractory Obsessive-compulsive Disorder (NCT NCT00523718)

NCT ID: NCT00523718

Last Updated: 2020-03-06

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: 14 weeks
• Results posted on: 2020-03-06

Participant Flow

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.

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.

Participant milestones

Measure	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 riluzole: 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. placebo: placebo, 1 capsule PO bid, 12 weeks
Overall Study STARTED	20	18
Overall Study COMPLETED	17	18
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Measure	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 riluzole: 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. placebo: placebo, 1 capsule PO bid, 12 weeks
Overall Study Withdrawal by Subject	1	0
Overall Study Protocol Violation	2	0

Baseline Characteristics

Riluzole Augmentation in Treatment-refractory Obsessive-compulsive Disorder

Baseline characteristics by cohort

Measure	Riluzole n=19 Participants 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	Placebo n=18 Participants 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 n=37 Participants Total of all reporting groups
Age, Continuous	41.5 years STANDARD_DEVIATION 3.2 • n=93 Participants	36.4 years STANDARD_DEVIATION 3.1 • n=4 Participants	38.52 years STANDARD_DEVIATION 13.80 • n=27 Participants
Sex: Female, Male Female	11 Participants n=93 Participants	9 Participants n=4 Participants	20 Participants n=27 Participants
Sex: Female, Male Male	8 Participants n=93 Participants	9 Participants n=4 Participants	17 Participants n=27 Participants
Race/Ethnicity, Customized White	19 participants n=93 Participants	16 participants n=4 Participants	35 participants n=27 Participants
Race/Ethnicity, Customized African American	0 participants n=93 Participants	2 participants n=4 Participants	2 participants n=27 Participants
Y-BOCS baseline score	30 units on a scale STANDARD_DEVIATION 5.12 • n=93 Participants	30.73 units on a scale STANDARD_DEVIATION 5.81 • n=4 Participants	30.37 units on a scale STANDARD_DEVIATION 5.41 • n=27 Participants
HDRS baseline score	12.68 units on a scale STANDARD_DEVIATION 6.89 • n=93 Participants	13.05 units on a scale STANDARD_DEVIATION 6.19 • n=4 Participants	12.87 units on a scale STANDARD_DEVIATION 6.46 • n=27 Participants
HARS baseline score	16.2 units on a scale STANDARD_DEVIATION 7.35 • n=93 Participants	15.95 units on a scale STANDARD_DEVIATION 6.433 • n=4 Participants	16.08 units on a scale STANDARD_DEVIATION 6.80 • n=27 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	Riluzole n=19 Participants 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	Placebo n=18 Participants 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
Partial Responders by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)	5 participants	2 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Riluzole n=19 Participants 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	Placebo n=18 Participants 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
Average Hamilton Depression Inventory (HAM-D)	11.941 units on a scale Standard Deviation 6.91	12.53 units on a scale Standard Deviation 5.67

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Riluzole n=19 Participants 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	Placebo n=18 Participants 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
Average Hamilton Anxiety Inventory (HAM-A)	14.176 units on a scale Standard Deviation 6.80	14.263 units on a scale Standard Deviation 6.19

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Riluzole n=19 Participants 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	Placebo n=18 Participants 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
Clinical Global Impression (CGI) - Severity of Illness Item	3.94 units on a scale Standard Deviation 1.09	3.95 units on a scale Standard Deviation 1.026

Adverse Events

Riluzole

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	Riluzole n=16 participants at risk；n=19 participants at risk 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	Placebo n=17 participants at risk；n=18 participants at risk 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
Psychiatric disorders Passively Suicidal	5.3% 1/19 • Number of events 1 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.	0.00% 0/18 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.
Psychiatric disorders Overdose of Narcotics	0.00% 0/19 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.	5.6% 1/18 • Number of events 1 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.

Other adverse events

Measure	Riluzole n=16 participants at risk；n=19 participants at risk 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	Placebo n=17 participants at risk；n=18 participants at risk 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
Gastrointestinal disorders Nausea	18.8% 3/16 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.	5.9% 1/17 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.
Nervous system disorders Poor Coordination	18.8% 3/16 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.	5.9% 1/17 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.
Gastrointestinal disorders Constipation	6.2% 1/16 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.	35.3% 6/17 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.
Cardiac disorders Pounding Heart Beat	0.00% 0/16 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.	17.6% 3/17 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.

Additional Information

Christopher Pittenger

Yale University

Phone: (203) 974-7675

Email: christopher.pittenger@yale.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place