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N-Acetylcysteine Augmentation in Treatment-Refractory Obsessive-Compulsive Disorder
This study is currently recruiting participants.
Verified by Yale University, October 2008
First Received: October 2, 2007   Last Updated: October 30, 2008   History of Changes
Sponsor: Yale University
Information provided by: Yale University
ClinicalTrials.gov Identifier: NCT00539513
  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 II

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment
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) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hamilton Depression Inventory (HAM-D) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Clinical Global Impression (CGI) - Severity of Illness item [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Hamilton Anxiety Inventory (HAM-A) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: June 2006
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
N-Acetylcysteine: Experimental
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
placebo: Placebo Comparator
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

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

Contacts
Contact: Suzanne Wasylink,, RN 203-974-7523
Contact: Eileen Billingslea, MA 203-974-7768 eileen.billingslea@yale.edu

Locations
United States, Connecticut
Yale OCD Research Clinic Recruiting
New Haven, Connecticut, United States, 06519
Contact: Suzanne Wasylink, RN     203-974-7523        
Principal Investigator: Christopher J Pittenger, MD, PhD            
Sub-Investigator: Gerard Sanacora, MD,PhD            
Sub-Investigator: Vladimir Coric, MD            
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Christopher J Pittenger, MD, Ph.D. Yale University
  More Information

Publications:
Responsible Party: Yale University ( Christopher Pittenger, MD, PhD; Principal Investigator )
Study ID Numbers: YOCD-2
Study First Received: October 2, 2007
Last Updated: October 30, 2008
ClinicalTrials.gov Identifier: NCT00539513     History of Changes
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
obsessive-compulsive disorder
OCD
glutamate
N-Acetylcysteine
augmentation

Additional relevant MeSH terms:
Acetylcysteine
N-monoacetylcystine
Anti-Infective Agents
Respiratory System Agents
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Antioxidants
Disease
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Protective Agents
Antiviral Agents
Serotonin Uptake Inhibitors
Pharmacologic Actions
Serotonin Agents
Pathologic Processes
Anxiety Disorders
Mental Disorders
Expectorants
Therapeutic Uses
Free Radical Scavengers
Obsessive-Compulsive Disorder
Antidotes

ClinicalTrials.gov processed this record on November 20, 2009