N-Acetylcysteine Augmentation in Treatment-Refractory Obsessive-Compulsive Disorder
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Obsessive-Compulsive Disorder |
Drug: N-Acetylcysteine Drug: placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Double-Blind Study of N-Acetylcysteine Augmentation in Serotonin Reuptake Inhibitor-Refractory Obsessive-Compulsive Disorder and Depression |
- Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
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.
- The Hamilton Depression Inventory (HAM-D)at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
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
| Enrollment: | 10 |
| Study Start Date: | June 2006 |
| Study Completion Date: | April 2011 |
| Primary Completion Date: | April 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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
|
Drug: N-Acetylcysteine
3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks
Other Name: NAC
|
|
Placebo Comparator: 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.
|
Drug: placebo
placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks
|
Detailed Description:
Due to limited participation, this study has closed.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts 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
Contacts and Locations More Information
Additional Information:
Publications:
| Responsible Party: | Christopher Pittenger, Principal Investigator, Yale University |
| ClinicalTrials.gov Identifier: | NCT00539513 History of Changes |
| Other Study ID Numbers: | YOCD-2 |
| Study First Received: | October 2, 2007 |
| Results First Received: | December 21, 2012 |
| Last Updated: | March 25, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Yale University:
|
obsessive-compulsive disorder OCD glutamate N-Acetylcysteine augmentation |
Additional relevant MeSH terms:
|
Obsessive-Compulsive Disorder Compulsive Personality Disorder Anxiety Disorders Mental Disorders Personality Disorders Acetylcysteine N-monoacetylcystine Serotonin Uptake Inhibitors Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions |
Expectorants Respiratory System Agents Free Radical Scavengers Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Physiological Effects of Drugs Antidotes Neurotransmitter Uptake Inhibitors Neurotransmitter Agents Serotonin Agents |
ClinicalTrials.gov processed this record on June 18, 2013