We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

N-Acetylcysteine Augmentation in Treatment-Refractory Obsessive-Compulsive Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00539513
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
Sponsor:
Information provided by (Responsible Party):
Yale University

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.


Condition or disease Intervention/treatment Phase
Obsessive-Compulsive Disorder Drug: N-Acetylcysteine Drug: placebo Phase 2

Detailed Description:
Due to limited participation, this study has closed.

Layout table for study information
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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.


  2. 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.



Secondary Outcome Measures :
  1. 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


  2. 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




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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


Sponsors and Collaborators
Yale University
Investigators
Layout table for investigator information
Principal Investigator: Christopher J Pittenger, MD, Ph.D. Yale University
Additional Information:
Publications:
Layout table for additonal information
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
Keywords provided by Yale University:
obsessive-compulsive disorder
OCD
glutamate
N-Acetylcysteine
augmentation
Additional relevant MeSH terms:
Layout table for MeSH terms
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