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

NCT00539513 | Terminated Phase 2 Results

• 1 other identifier: 0603001215
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Obsessive-Compulsive Disorder

Keywords

obsessive-compulsive disorder; OCD; glutamate; N-Acetylcysteine; augmentation

Outcome Measures

Primary Outcomes (2)

• Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at 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.

  Baseline

• Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at 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.

  12 Weeks

Secondary Outcomes (2)

• The Hamilton Depression Inventory (HAM-D)at Baseline

  Baseline

• The Hamilton Depression Inventory (HAM-D)at 12 Weeks

  12 weeks

Study Arms (2)

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

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

Interventions

N-Acetylcysteine DRUG

3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks

Also known as: NAC

N-Acetylcysteine

placebo DRUG

placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead

Related Publications (3)

• Pittenger C, Krystal JH, Coric V. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder. NeuroRx. 2006 Jan;3(1):69-81. doi: 10.1016/j.nurx.2005.12.006.

  PMID: 16490414 BACKGROUND

• Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, Saksa J, Wu YT, Gueorguieva R, Sanacora G, Malison RT, Krystal JH. Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005 Sep 1;58(5):424-8. doi: 10.1016/j.biopsych.2005.04.043.

  PMID: 15993857 BACKGROUND

• Pittenger C, Bloch MH, Williams K. Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment. Pharmacol Ther. 2011 Dec;132(3):314-32. doi: 10.1016/j.pharmthera.2011.09.006. Epub 2011 Sep 22.

  PMID: 21963369 BACKGROUND

Related Links

• Yale OCD Research Clinic site
• Related Info

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Christopher Pittenger, MD Ph.D
• Organization: Yale University School of Medicine

christopher.pittenger@yale.edu

203-974-7675

Study Officials

• Christopher J Pittenger, MD, Ph.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2007
• First Posted: October 4, 2007
• Study Start: June 1, 2006
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: April 2, 2020
• Results First Posted: March 8, 2013

Record last verified: 2020-03