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

This study has been terminated.
(Researchers terminated study due to limited enrollment.)
Sponsor:
Information provided by (Responsible Party):
Christopher Pittenger, Yale University
ClinicalTrials.gov Identifier:
NCT00539513
First received: October 2, 2007
Last updated: March 25, 2013
Last verified: March 2013
  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

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00539513

Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Christopher J Pittenger, MD, Ph.D. Yale University
  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:
Compulsive Personality Disorder
Disease
Obsessive-Compulsive Disorder
Anxiety Disorders
Mental Disorders
Pathologic Processes
Personality Disorders
Acetylcysteine
N-monoacetylcystine
Serotonin Uptake Inhibitors
Anti-Infective Agents
Antidotes
Antioxidants
Antiviral Agents
Expectorants
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Serotonin Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014