NAC for Treatment-Resistant OCD and Other Related Disorders

NCT ID: NCT06956157

Last Updated: 2025-09-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-22
• Study Completion Date: 2025-11-13

Brief Summary

This is a randomized, double-blind, placebo-controlled study investigating N-acetylcysteine (NAC) as an augmentation therapy for individuals with treatment-resistant obsessive-compulsive disorder (TR-OCD), studied within a broader cohort of treatment-resistant Obsessive-Compulsive and Related Disorders (OCRDs).

The study's primary aim is to investigate the neurobiological mechanism by which NAC improves inhibitory control deficits in TR-OCD. This is achieved by using Magnetic Resonance Spectroscopy (MRS) to measure changes in thalamic glutamatergic metabolism. A secondary aim is to assess the clinical efficacy of this augmentation strategy on symptom severity. The central hypothesis is that improvements in inhibitory control are mediated by NAC-induced changes in brain glutamate levels.

Detailed Description

Please note: This study was initially designed to investigate the effects of N-acetylcysteine (NAC) across the broader spectrum of treatment-resistant Obsessive-Compulsive and Related Disorders (OCRDs), including cohorts such as Excoriation (Skin-Picking) Disorder. The overarching scientific objective was to use NAC to elucidate the neurobiological mechanisms underlying inhibitory control deficits in this difficult-to-treat population, and thereby inform the development of novel therapeutic strategies.

Upon completion of recruitment for the current analysis phase and prior to any unblinking, we finalized our analytical strategy. To ensure the primary analysis was adequately powered to yield a definitive conclusion, it was focused on the treatment-resistant OCD (TR-OCD) cohort, which comprised the substantial majority of the sample accrued to date.

Consequently, the TR-OCD cohort was designated as the primary population for the main efficacy and mechanistic analyses. Other OCRD subgroups enrolled under the same protocol were designated for planned secondary and exploratory analyses, in line with their respective sample sizes. Analyses of these subgroups, including the SPD cohort, will be conducted once sufficient data have been accrued for robust statistical testing.

This registration has been updated to accurately and transparently reflect this final, pre-specified analytical plan, ensuring the public record aligns with the study's primary, hypothesis-driven conclusions.

Conditions

Obsessive Compulsive Disorder (OCD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

N-acetylcysteine group

NAC (N-Acetylcysteine Tablets, brand name: Flumucil) has a drug specification of 600 mg per tablet. In the first week, participants took 1200mg/d (one tablet three times daily: morning, noon, and evening). Starting from the second week until the end of the 12-week study, they took 3600mg/d (three tablets twice daily: morning and evening).

Group Type: EXPERIMENTAL

N-Acetylcysteine Tablets

Intervention Type: DRUG

In addition to participants' existing medication regimens, NAC will be added.

Placebo group

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Placebo oral tablets are identical in appearance (size, shape, color), packaging, taste, and administration schedule to the N-Acetylcysteine tablets to maintain blinding. The tablets contain inert excipients and no active pharmacological ingredients.

Healthy Control Group

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

N-Acetylcysteine Tablets

In addition to participants' existing medication regimens, NAC will be added.

Intervention Type: DRUG

Placebo Oral Tablet

Placebo oral tablets are identical in appearance (size, shape, color), packaging, taste, and administration schedule to the N-Acetylcysteine tablets to maintain blinding. The tablets contain inert excipients and no active pharmacological ingredients.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

(1) Age between 12 and 55 years. (2) A primary diagnosis of OCD according to DSM-5 criteria. (3) Excoriation (Skin-Picking) Disorder (SPD) according to DSM-5 criteria.

(4) Met criteria for treatment resistance, defined as: (a) A Y-BOCS score ≥ 16. (b) A history of inadequate response (<25% reduction in Y-BOCS score) to at least two different serotonin reuptake inhibitors (SSRIs) at an adequate dose for at least 12 weeks each.

(1) Age and sex-matched to the patient group. (2) No personal history of any psychiatric disorder.

Exclusion Criteria

(1) Current or lifetime diagnosis of a primary psychotic disorder (e.g., schizophrenia), bipolar I/II disorder, or intellectual disability. (2) Any contraindication to the use of N-acetylcysteine.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Guangdong Provincial People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

sunnyrong

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Huirong Zheng, MD

Role: PRINCIPAL_INVESTIGATOR

Guangdong Provincial People's Hospital

Locations

Guangdong Mental Health Center, Guangdong Provincial People's Hospital

GuangDong, Guangdong, China

Countries

China

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

2021A1515011431

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

KY2020-572

Identifier Type: -

Identifier Source: org_study_id