N-Acetylcysteine Augmentation in Treatment-Refractory Obsessive-Compulsive Disorder
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| ClinicalTrials.gov Identifier: NCT00539513 |
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Recruitment Status :
Terminated
(Researchers terminated study due to limited enrollment.)
First Posted : October 4, 2007
Results First Posted : March 8, 2013
Last Update Posted : April 2, 2020
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Obsessive-Compulsive Disorder | Drug: N-Acetylcysteine Drug: placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 10 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 N-Acetylcysteine Augmentation in Serotonin Reuptake Inhibitor-Refractory Obsessive-Compulsive Disorder and Depression |
| Study Start Date : | June 2006 |
| Actual Primary Completion Date : | April 2011 |
| Actual Study Completion Date : | April 2011 |
| Arm | Intervention/treatment |
|---|---|
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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
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Drug: N-Acetylcysteine
3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks
Other Name: NAC |
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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.
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Drug: placebo
placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks |
- Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at Baseline [ Time Frame: 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 [ Time Frame: 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.
- The Hamilton Depression Inventory (HAM-D)at Baseline [ Time Frame: 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 [ Time Frame: 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
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00539513
| Principal Investigator: | Christopher J Pittenger, MD, Ph.D. | Yale University |
Publications:
| Responsible Party: | Yale University |
| ClinicalTrials.gov Identifier: | NCT00539513 |
| Other Study ID Numbers: |
0603001215 |
| First Posted: | October 4, 2007 Key Record Dates |
| Results First Posted: | March 8, 2013 |
| Last Update Posted: | April 2, 2020 |
| Last Verified: | March 2020 |
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obsessive-compulsive disorder OCD glutamate N-Acetylcysteine augmentation |
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Disease Compulsive Personality Disorder Obsessive-Compulsive Disorder Pathologic Processes Personality Disorders Mental Disorders Anxiety Disorders Acetylcysteine N-monoacetylcystine Antiviral Agents |
Anti-Infective Agents Expectorants Respiratory System Agents Free Radical Scavengers Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Physiological Effects of Drugs Antidotes |