Obsessive-Compulsive Disorder
Conditions
Keywords
obsessive-compulsive disorder, OCD, glutamate, N-Acetylcysteine, augmentation
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 researchers 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 N-Acetylcysteine, whose glutamatergic antagonistic properties may be effective in reducing the glutamatergic hyperactivity that is thought to contribute to the pathophysiology of OCD and major depressive disorder (MDD). Riluzole, which is FDA approved for amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease) is also a glutamatergic agent. There is evidence that riluzole possesses anti-depressant, anti-obsessional, and anti-anxiety properties. The modulation of glutamatergic activity is a promising new approach to the treatment of mood disorders. The researchers are therefore now recruiting patients to participate in a double-blind, placebo-controlled trial of N-Acetylcysteine, added to whatever other OCD medications they are taking.
Detailed description
Due to limited participation, this study has closed.
Interventions
DRUGN-Acetylcysteine
3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks
DRUGplacebo
placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks
Sponsors
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
* DSM-IV diagnosis of OCD, confirmed by SCID-IV; symptoms of at least 1 year duration * moderate to severe OCD symptoms (Y-BOCS \> 16) * documented failure of an adequate trial of an 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 N-Acetylcysteine * 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 |
|---|---|---|
| Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at Baseline | Baseline | The Y-BOCS is a 10 item clinician-rated scale used to both determine the severity of OCD and to monitor symptom improvement throughout the course of the study. The Y-BOCS, specifically measures the severity of symptoms of obsessive-compulsive disorder without being biased towards the type of obsessions or compulsions present. The scale includes questions about the amount of time spent on, how much impairment or distress experienced from, and how much resistance and control over these obsessive thoughts and compulsions. Each item is rated from 0 (no symptoms) to 4 (extreme symptoms) and yields a total possible score range from 0 to 40, with the following ranges indicating degree of severity: 0-7 = sub-clinical 8-15 = mild 16-23 = moderate 24-31 = severe 32-40 = extreme In this study, baseline ratings are compared to those of week 12 to produce a percent of change with positive percentages indicating a decrease in symptom severity. |
| Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at 12 Weeks | 12 Weeks | The Y-BOCS is a 10 item clinician-rated scale used to both determine the severity of OCD and to monitor symptom improvement throughout the course of the study. The Y-BOCS, specifically measures the severity of symptoms of obsessive-compulsive disorder without being biased towards the type of obsessions or compulsions present. The scale includes questions about the amount of time spent on, how much impairment or distress experienced from, and how much resistance and control over these obsessive thoughts and compulsions. Each item is rated from 0 (no symptoms) to 4 (extreme symptoms) and yields a total possible score range from 0 to 40, with the following ranges indicating degree of severity: 0-7 = sub-clinical 8-15 = mild 16-23 = moderate 24-31 = severe 32-40 = extreme In this study, baseline ratings are compared to those of week 12 to produce a percent of change with positive percentages indicating a decrease in symptom severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Hamilton Depression Inventory (HAM-D)at Baseline | Baseline | The Hamilton Rating Scale for Depression is a multiple item (traditionally 17) assessment used to provide an indication of depression and as a guide to evaluate recovery. The clinician-rated assessment is designed for adults and is used to rate the severity of patient depression by asking about mood, feelings of guilt, insomnia, agitation, weight change, suicidal ideation, and somatic symptoms. The scale also allows the clinician to assess the patient's level of retardation, and insight into their depression. In this study, the HAM-D17 (17 items scored) was used to obtain depression severity ratings with a maximum possible score of 52. Baseline ratings are compared to those of week 12 to produce a percentage of change, where positive values indicate a decrease in depressive severity/symptoms. Maximum score is a 52. Ranges 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression ≥23 = Very Severe Depression |
| The Hamilton Depression Inventory (HAM-D)at 12 Weeks | 12 weeks | The Hamilton Rating Scale for Depression is a multiple item (traditionally 17) assessment used to provide an indication of depression and as a guide to evaluate recovery. The clinician-rated assessment is designed for adults and is used to rate the severity of patient depression by asking about mood, feelings of guilt, insomnia, agitation, weight change, suicidal ideation, and somatic symptoms. The scale also allows the clinician to assess the patient's level of retardation, and insight into their depression. In this study, the HAM-D17 (17 items scored) was used to obtain depression severity ratings with a maximum possible score of 52. Baseline ratings are compared to those of week 12 to produce a percentage of change, where positive values indicate a decrease in depressive severity/symptoms. Maximum score is a 52. Ranges 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression ≥23 = Very Severe Depression |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| N-Acetylcysteine Patients randomized to this arm will receive N-Acetylcysteine augmentation, at a standard dose titrated to 3000 mg within the first week, in addition to the medication regimen they are on at enrollment
N-Acetylcysteine : 3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks | 5 |
| Placebo Patients randomized to this arm will receive placebo, formulated to be indistinguishable from N-Acetylcysteine, in addition to the medication regimen they are on at study enrollment.
placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks | 5 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | N-Acetylcysteine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 3 | 0 / 4 |
| serious Total, serious adverse events | 0 / 3 | 0 / 4 |
Outcome results
Primary
Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at 12 Weeks
The Y-BOCS is a 10 item clinician-rated scale used to both determine the severity of OCD and to monitor symptom improvement throughout the course of the study. The Y-BOCS, specifically measures the severity of symptoms of obsessive-compulsive disorder without being biased towards the type of obsessions or compulsions present. The scale includes questions about the amount of time spent on, how much impairment or distress experienced from, and how much resistance and control over these obsessive thoughts and compulsions. Each item is rated from 0 (no symptoms) to 4 (extreme symptoms) and yields a total possible score range from 0 to 40, with the following ranges indicating degree of severity: 0-7 = sub-clinical 8-15 = mild 16-23 = moderate 24-31 = severe 32-40 = extreme In this study, baseline ratings are compared to those of week 12 to produce a percent of change with positive percentages indicating a decrease in symptom severity.
Time frame: 12 Weeks
Population: Participants who completed the intervention were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-Acetylcysteine | Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at 12 Weeks | 30.6 units on a scale | Standard Deviation 7.6 |
| Placebo | Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at 12 Weeks | 28.7 units on a scale | Standard Deviation 1.6 |
Primary
Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at Baseline
The Y-BOCS is a 10 item clinician-rated scale used to both determine the severity of OCD and to monitor symptom improvement throughout the course of the study. The Y-BOCS, specifically measures the severity of symptoms of obsessive-compulsive disorder without being biased towards the type of obsessions or compulsions present. The scale includes questions about the amount of time spent on, how much impairment or distress experienced from, and how much resistance and control over these obsessive thoughts and compulsions. Each item is rated from 0 (no symptoms) to 4 (extreme symptoms) and yields a total possible score range from 0 to 40, with the following ranges indicating degree of severity: 0-7 = sub-clinical 8-15 = mild 16-23 = moderate 24-31 = severe 32-40 = extreme In this study, baseline ratings are compared to those of week 12 to produce a percent of change with positive percentages indicating a decrease in symptom severity.
Time frame: Baseline
Population: Participants who completed the intervention were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-Acetylcysteine | Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at Baseline | 30.3 units on a scale | Standard Deviation 5.7 |
| Placebo | Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at Baseline | 28.6 units on a scale | Standard Deviation 5 |
Secondary
The Hamilton Depression Inventory (HAM-D)at 12 Weeks
The Hamilton Rating Scale for Depression is a multiple item (traditionally 17) assessment used to provide an indication of depression and as a guide to evaluate recovery. The clinician-rated assessment is designed for adults and is used to rate the severity of patient depression by asking about mood, feelings of guilt, insomnia, agitation, weight change, suicidal ideation, and somatic symptoms. The scale also allows the clinician to assess the patient's level of retardation, and insight into their depression. In this study, the HAM-D17 (17 items scored) was used to obtain depression severity ratings with a maximum possible score of 52. Baseline ratings are compared to those of week 12 to produce a percentage of change, where positive values indicate a decrease in depressive severity/symptoms. Maximum score is a 52. Ranges 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression ≥23 = Very Severe Depression
Time frame: 12 weeks
Population: Participants that completed the study were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-Acetylcysteine | The Hamilton Depression Inventory (HAM-D)at 12 Weeks | 12.1 units on a scale | Standard Deviation 8.2 |
| Placebo | The Hamilton Depression Inventory (HAM-D)at 12 Weeks | 7.0 units on a scale | Standard Deviation 6.6 |
Secondary
The Hamilton Depression Inventory (HAM-D)at Baseline
The Hamilton Rating Scale for Depression is a multiple item (traditionally 17) assessment used to provide an indication of depression and as a guide to evaluate recovery. The clinician-rated assessment is designed for adults and is used to rate the severity of patient depression by asking about mood, feelings of guilt, insomnia, agitation, weight change, suicidal ideation, and somatic symptoms. The scale also allows the clinician to assess the patient's level of retardation, and insight into their depression. In this study, the HAM-D17 (17 items scored) was used to obtain depression severity ratings with a maximum possible score of 52. Baseline ratings are compared to those of week 12 to produce a percentage of change, where positive values indicate a decrease in depressive severity/symptoms. Maximum score is a 52. Ranges 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression ≥23 = Very Severe Depression
Time frame: Baseline
Population: Participants that completed the study were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-Acetylcysteine | The Hamilton Depression Inventory (HAM-D)at Baseline | 17.3 units on a scale | Standard Deviation 2.3 |
| Placebo | The Hamilton Depression Inventory (HAM-D)at Baseline | 8.7 units on a scale | Standard Deviation 10.2 |