Obsessive-compulsive Disorder, Ocd
Conditions
Keywords
obsessive-compulsive disorder, OCD, glutamate, riluzole, augmentation, 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.
Interventions
DRUGriluzole
50 mg PO bid, 12 weeks
DRUGplacebo
placebo, 1 capsule PO bid, 12 weeks
Sponsors
National Institute of Mental Health (NIMH)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 19 |
| 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 | 18 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Riluzole | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 41.5 years STANDARD_DEVIATION 3.2 | 36.4 years STANDARD_DEVIATION 3.1 | 38.52 years STANDARD_DEVIATION 13.8 |
| HARS baseline score | 16.2 units on a scale STANDARD_DEVIATION 7.35 | 15.95 units on a scale STANDARD_DEVIATION 6.433 | 16.08 units on a scale STANDARD_DEVIATION 6.8 |
| HDRS baseline score | 12.68 units on a scale STANDARD_DEVIATION 6.89 | 13.05 units on a scale STANDARD_DEVIATION 6.19 | 12.87 units on a scale STANDARD_DEVIATION 6.46 |
| Race/Ethnicity, Customized African American | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized White | 19 participants | 16 participants | 35 participants |
| Sex: Female, Male Female | 11 Participants | 9 Participants | 20 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
| Y-BOCS baseline score | 30 units on a scale STANDARD_DEVIATION 5.12 | 30.73 units on a scale STANDARD_DEVIATION 5.81 | 30.37 units on a scale STANDARD_DEVIATION 5.41 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 16 | 11 / 17 |
| serious Total, serious adverse events | 1 / 19 | 1 / 18 |
Outcome results
Primary
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
Time frame: 14 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Riluzole | Partial Responders by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) | 5 participants |
| Placebo | Partial Responders by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) | 2 participants |
p-value: 0.24Chi-squared
Secondary
Average Hamilton Anxiety Inventory (HAM-A)
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riluzole | Average Hamilton Anxiety Inventory (HAM-A) | 14.176 units on a scale | Standard Deviation 6.8 |
| Placebo | Average Hamilton Anxiety Inventory (HAM-A) | 14.263 units on a scale | Standard Deviation 6.19 |
Secondary
Average Hamilton Depression Inventory (HAM-D)
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riluzole | Average Hamilton Depression Inventory (HAM-D) | 11.941 units on a scale | Standard Deviation 6.91 |
| Placebo | Average Hamilton Depression Inventory (HAM-D) | 12.53 units on a scale | Standard Deviation 5.67 |
Secondary
Clinical Global Impression (CGI) - Severity of Illness Item
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riluzole | Clinical Global Impression (CGI) - Severity of Illness Item | 3.94 units on a scale | Standard Deviation 1.09 |
| Placebo | Clinical Global Impression (CGI) - Severity of Illness Item | 3.95 units on a scale | Standard Deviation 1.026 |