Obsessive-Compulsive DisorderPhase 2NCT00539513

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

A Phase 2 study testing N-Acetylcysteine in people with Obsessive-Compulsive Disorder, run by Yale University.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Obsessive-Compulsive Disorder
What is being tested?: N-Acetylcysteine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 10 participants
Where: No sites listed yet
Study dates: Jun 2006to Apr 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

Show all 10Show fewer

liver function tests (LFTs) elevated to more than 2x the upper limit of normal
evidence of active liver disease
seizure disorder
active suicidal ideation

About this study

Official title: A Double-Blind Study of N-Acetylcysteine Augmentation in Serotonin Reuptake Inhibitor-Refractory Obsessive-Compulsive Disorder and Depression

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.

Read the detailed description

Due to limited participation, this study has closed.

Conditions: Obsessive-Compulsive Disorder
Being tested: N-Acetylcysteine, placebo
Keywords: obsessive-compulsive disorder, OCD, glutamate, N-Acetylcysteine, augmentation
Medical subject headings: Obsessive-Compulsive Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

N-AcetylcysteineDrug
Also called NAC
3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks
placeboDrug
placebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks

Study groups in NCT00539513
Study group	Role	What they receive
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 Receives: 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. Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 12 Weeks

Secondary outcomes (2)

The Hamilton Depression Inventory (HAM-D)at 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
Measured: Baseline
The Hamilton Depression Inventory (HAM-D)at 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
Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2006Apr 2011

First posted4 Oct 2007 (estimated)
Study startJun 2006
Primary completionApr 2011
Study completionApr 2011

Why it stopped: Researchers terminated study due to limited enrollment.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Obsessive-Compulsive DisorderStudies of the same condition, open and under way.
More trials run by Yale UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00539513
Sponsor's protocol ID: 0603001215
Status last verified: Mar 2020
First submitted: 2 Oct 2007
Last updated: 2 Apr 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 16490414
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.
PubMed 15993857
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.
PubMed 21963369

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Enrolling by invitation
Family Accommodation Reduction in Adult Obsessive Compulsive Disorder
Obsessive - Compulsive Disorder, Family Accommodation
Not yet recruitingObservational study
Investigation of Obsessive-Compulsive Disorder in Patients With Elbow Epicondylitis
Lateral Epicondylitis, Medial Epicondylitis
Recruiting
Precision Analytic Research Methods in OCD
Obsessive Compulsive Disorder
Recruiting
Focused Ultrasound for Behavioral Health
Depression, Anxiety
Not yet recruiting
Linear Accelerator Radiosurgical Anterior Capsulotomy With Task-based fMRI Identification of PERSonalized and PrEdictiVE Biomarkers of REsponse in Treatment-Refractory Obsessive-Compulsive Disorder (PERSEVERE Trial)
Treatment-refractory Obsessive-compulsive Disorder (trOCD)

All Obsessive-Compulsive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-Blind Study of N-Acetylcysteine Augmentation in Serotonin Reuptake Inhibitor-Refractory Obsessive-Compulsive Disorder and Depression
ClinicalTrials.gov ID: NCT00539513
Acronym / sponsor ID: 0603001215
Conditions: Obsessive-Compulsive Disorder
Keywords: obsessive-compulsive disorder, OCD, glutamate, N-Acetylcysteine, augmentation
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Researchers terminated study due to limited enrollment.
Enrolment: 10 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Study start: Jun 2006
Primary completion: Apr 2011 (actual)
Study completion: Apr 2011 (actual)
First posted: 4 Oct 2007 (estimated)
Results: Posted 8 Mar 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Due to limited participation, this study has closed.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
N-Acetylcysteine	Experimental	Drug: N-AcetylcysteinePatients 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
placebo	Placebo comparator	Drug: placeboPatients 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.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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)

Key exclusion criteria (10 listed)

primary diagnosis of a psychotic disorder
active substance abuse or dependence
unstable medical condition
prior exposure to N-Acetylcysteine
prior psychosurgery

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
N-AcetylcysteineAlso: NAC3000 mg by mouth PO (1200 mg AM, 1800 mg PM), 12 weeks	Drug	N-Acetylcysteine
placeboplacebo, 2 capsules PO AM, 3 capsules PO PM, 12 weeks	Drug	placebo

Primary outcome

Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at Baseline
Time frame: 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.
Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at 12 Weeks
Time frame: 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.

2 secondary outcomes

The Hamilton Depression Inventory (HAM-D)at Baseline
Time frame: Baseline
The Hamilton Depression Inventory (HAM-D)at 12 Weeks
Time frame: 12 weeks

Results and safety

Results posted to the registry on 8 Mar 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
N-Acetylcysteine	5	3
Placebo	5	3

Primary outcome: Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at Baseline

Time frame: Baseline. Mean (Standard Deviation). Unit: units on a scale

Measure	N-Acetylcysteine n = 3	Placebo n = 3
Value	30.3 (5.7)	28.6 (5.0)

Population analysed: Participants who completed the intervention were included in the analysis

Primary outcome: Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at 12 Weeks

Time frame: 12 Weeks. Mean (Standard Deviation). Unit: units on a scale

Measure	N-Acetylcysteine n = 3	Placebo n = 3
Value	30.6 (7.6)	28.7 (1.6)

Population analysed: Participants who completed the intervention were included in the analysis

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
N-Acetylcysteine	0 of 3 (0%)	0 of 3 (0%)	Not reported
Placebo	0 of 4 (0%)	0 of 4 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16490414Pittenger 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.
Background: PubMed 15993857Coric 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.
Background: PubMed 21963369Pittenger 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.
Yale OCD Research Clinic siteLink provided by the sponsor.
Related InfoLink provided by the sponsor.

Related trials for Obsessive-Compulsive Disorder

Enrolling by invitation
Family Accommodation Reduction in Adult Obsessive Compulsive Disorder
Obsessive - Compulsive Disorder, Family Accommodation
Not yet recruitingObservational study
Investigation of Obsessive-Compulsive Disorder in Patients With Elbow Epicondylitis
Lateral Epicondylitis, Medial Epicondylitis
Recruiting
Precision Analytic Research Methods in OCD
Obsessive Compulsive Disorder
Recruiting
Focused Ultrasound for Behavioral Health
Depression, Anxiety
Not yet recruiting
Linear Accelerator Radiosurgical Anterior Capsulotomy With Task-based fMRI Identification of PERSonalized and PrEdictiVE Biomarkers of REsponse in Treatment-Refractory Obsessive-Compulsive Disorder (PERSEVERE Trial)
Treatment-refractory Obsessive-compulsive Disorder (trOCD)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Christopher J Pittenger, MD, Ph.D. principal investigator

Yale University

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing N-Acetylcysteine in people with Obsessive-Compulsive Disorder, run by Yale University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)at Baseline (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00539513, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2020.