Clinical trial NCT00539513: N-Acetylcysteine Augmentation in Treatment-Refractory Obsessive-Compulsive Disorder
Official title: A Double-Blind Study of N-Acetylcysteine Augmentation in Serotonin Reuptake Inhibitor-Refractory Obsessive-Compulsive Disorder and Depression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Obsessive-Compulsive Disorder
Keywords: obsessive-compulsive disorder
OCD
glutamate
N-Acetylcysteine
augmentation
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2007-10-04
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility 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

Primary outcomes:
measure: Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at Baseline
timeFrame: Baseline
measure: Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at 12 Weeks
timeFrame: 12 Weeks
Secondary outcomes:
measure: The Hamilton Depression Inventory (HAM-D)at Baseline
timeFrame: Baseline
measure: The Hamilton Depression Inventory (HAM-D)at 12 Weeks
timeFrame: 12 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Yale University
name: Christopher J Pittenger, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.