NAC for Treatment-Resistant OCD and Other Related Disorders

Phase 4

Active, not recruiting

• Conditions: Obsessive Compulsive Disorder (OCD)
• Interventions: Drug: N-Acetylcysteine Tablets; Drug: Placebo Oral Tablet

• Registration Number: NCT06956157
• Lead Sponsor: Guangdong Provincial People's Hospital

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.

Study Timeline

• Study Start: 2022-06-22
• Primary Completion: 2024-11-13
• Study First Submitted: 2025-04-25
• Study First Submitted QC: 2025-04-25
• Study First Posted: 2025-05-04
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-01
• Last Update Posted: 2025-09-03
• Study Completion: 2025-11-13

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
N-acetylcysteine group	N-Acetylcysteine Tablets	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).
Placebo group	Placebo Oral Tablet	-

Primary Outcome Measures

Name	Time	Method
Change from Baseline in Neurometabolite Concentrations in Key Brain Regions	Baseline, Post-treatment (Week 12)	Change from baseline to Week 12 in the concentrations of Glutamate (Glu), Glutamate+Glutamine (Glx), and Glutathione (GSH) within two pre-specified regions of interest: the thalamus and the anterior cingulate cortex (ACC). Levels are measured in both resting and functional states using Magnetic Resonance Spectroscopy (MRS).
Change from Baseline in Inhibitory Control Performance	Baseline, Post-treatment (Week 12)	Change from baseline to Week 12 in inhibitory control performance, as measured by the error rate on a Go-Nogo task. A decrease in the error rate indicates improvement.

Secondary Outcome Measures

Name	Time	Method
Yale-Brown Obsessive Compulsive Scale	Baseline, Week 4, Week 8, Week 12	Change in the total score of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) from baseline. Scores range from 0 to 40, with higher scores indicating greater symptom severity.
Yale-Brown Obsessive Compulsive Scale modified for Neurotic Excoriation	Baseline, Week 4, Week 8, Week 12	Proportion of participants achieving a predefined percentage reduction in the total score from baseline to post-treatment.

Trial Locations

Locations (1)

Guangdong Mental Health Center, Guangdong Provincial People's Hospital; 🇨🇳 GuangDong, Guangdong, China

Guangdong Mental Health Center, Guangdong Provincial People's Hospital

🇨🇳GuangDong, Guangdong, China