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

• Sponsor: Yale University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00539513
• Collaborator: (none)
• Enrollment: 10
• Arms: 2
• Duration (Months): 58

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• 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: Jun 1, 2006
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

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 Names: 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

Outcome Measures

Primary Outcome Measures

1. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at Baseline [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 [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 [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 [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

No locations specified.

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Christopher J Pittenger, MD, Ph.D., Yale University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Yale OCD Research Clinic site
• Related Info

Publications

• 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.
• 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. Review.
• 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. Review.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00539513
• Other Study ID Numbers: 0603001215
• First Posted: Oct 4, 2007
• Last Update Posted: Apr 2, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by Yale University: obsessive-compulsive disorder; OCD; glutamate; N-Acetylcysteine; augmentation
• Additional relevant MeSH terms: Disease; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Acetylcysteine; N-monoacetylcystine

Study Results

Participant Flow

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	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 N-Acetylcysteine : 3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks	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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks
Period Title: Overall Study
STARTED	5	5
Received Allocated Intervention	3	4
COMPLETED	3	3
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	N-Acetylcysteine	Placebo	Total
Arm/Group Description	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 N-Acetylcysteine : 3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks	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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks	Total of all reporting groups
Overall Participants	5	5	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	5 100%	10 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 40%	2 40%	4 40%
Male	3 60%	3 60%	6 60%

Outcome Measures

1. Primary Outcome

Title	Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at Baseline
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Participants who completed the intervention were included in the analysis

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	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 N-Acetylcysteine : 3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks	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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks
Measure Participants	3	3
Mean (Standard Deviation) [units on a scale]	30.3 (5.7)	28.6 (5.0)

2. Secondary Outcome

Title	The Hamilton Depression Inventory (HAM-D)at Baseline
Description	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
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Participants that completed the study were analyzed

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	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 N-Acetylcysteine : 3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks	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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks
Measure Participants	3	3
Mean (Standard Deviation) [units on a scale]	17.3 (2.3)	8.7 (10.2)

3. Primary Outcome

Title	Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at 12 Weeks
Description	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.
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

Participants who completed the intervention were included in the analysis

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	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 N-Acetylcysteine : 3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks	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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks
Measure Participants	3	3
Mean (Standard Deviation) [units on a scale]	30.6 (7.6)	28.7 (1.6)

4. Secondary Outcome

Title	The Hamilton Depression Inventory (HAM-D)at 12 Weeks
Description	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
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Participants that completed the study were analyzed

Arm/Group Title	N-Acetylcysteine	Placebo
Arm/Group Description	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 N-Acetylcysteine : 3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks	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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks
Measure Participants	3	3
Mean (Standard Deviation) [units on a scale]	12.1 (8.2)	7.0 (6.6)

Adverse Events

Arm/Group Title	N-Acetylcysteine		Placebo
Arm/Group Description	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 N-Acetylcysteine : 3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks		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. placebo : placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks
All Cause Mortality
	N-Acetylcysteine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	N-Acetylcysteine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	N-Acetylcysteine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.