Effects of NAC on Symptoms of CHR Patients

Status Recruiting

Clinical Trial Summary

Schizophrenia is a chronic debilitating psychotic disorder. Identifying persons with "clinical high-risk" (CHR) symptoms, which are like those of schizophrenia but less severe, and providing psychiatric care to these individuals has been shown to help prevent psychosis. Current medications used for CHR symptoms, however, are associated with substantial side effect burden. Therefore, practice guidelines do not recommend current medications as routine treatment for the CHR state, and there is a need to identify new treatments for this condition. Research suggests that abnormal brain oxidative stress may contribute to schizophrenia, offering a potential novel treatment target in the CHR state. Oxidative stress is an excess of free radicals, which are generated from normal metabolism and environmental exposures, and can damage cells. Antioxidants in the body normally neutralize free radicals. Antioxidant deficiency could result in excess oxidative stress that damages brain cells, leading to schizophrenia. Recent studies suggest that N-acetylcysteine (NAC), a precursor of the most abundant brain antioxidant, glutathione, may be a safe, well-tolerated treatment for schizophrenia. In light of this, NAC may also reduce symptoms and brain abnormalities in CHR patients.

Clinical Trial Description

The primary aim is to examine the effect of NAC on psychosis-like symptoms in CHR patients. Secondary aims are to examine the effect of NAC, in these patients, on the amplitude of the mismatch negativity (MMN), an electroencephalographic event-related potential (ERP) response to rare sounds among frequent ones; and the amplitude of the N400 semantic priming effect, an ERP response to unexpected compared to expected meaningful stimuli (e.g., words, pictures); both of which have been found to be reduced in both schizophrenia and the CHR state. This will be a randomized, double-blind, placebo-controlled trial. Ninety CHR patients will take either NAC 2000 mg orally or placebo, daily for 8 weeks. Psychosis-like symptoms will be assessed at baseline, week 4 and week 8 using the Positive symptom score of the Scale of Psychosis-Risk Symptoms in the Structured Interview for Psychosis-Risk Syndromes. MMN amplitude and the N400 semantic priming effect will be measured at baseline and week 8. We hypothesize that patients will have more improvement in psychosis-like symptoms, and greater increases in MMN amplitudes and N400 semantic priming effects, after taking NAC vs. placebo. If we find that NAC improves psychosis-like symptoms and/or these neurophysiological biomarkers of the CHR state, this would support further research on NAC as a preventive treatment against psychosis. ;

Study Design

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT05142735
Study type	Interventional
Source	Centre for Addiction and Mental Health
Contact	Michael Kiang, MD, PhD
Phone	416-535-8501
Email	michael.kiang@camh.ca
Status	Recruiting
Phase	N/A
Start date	January 13, 2023
Completion date	December 31, 2024

View Details

See also
Status	Clinical Trial	Phase
Terminated	`NCT03149107` - "Multimodal Prevention of Psychosis - Investigating Efficacy of N-Acetylcysteine and Psychotherapy in CHR-Patients"	Phase 3
Recruiting	`NCT05131035` - Targeting Processing Speed Deficits to Improve Social Functioning and Lower Psychosis Risk	N/A
Completed	`NCT01269710` - Second-Generation Antipsychotic Treatment Indication Effectiveness And Tolerability In Youth (Satiety) Study	N/A
Enrolling by invitation	`NCT05567848` - Accelerated TMS in Psychosis	Phase 1/Phase 2
Recruiting	`NCT03751865` - Early Detection and Intervention for Women At-risk of Psychosis	N/A
Recruiting	`NCT05052853` - Early Intervention of Prodromal Schizophrenia Using an NMDA Enhancer	Phase 2
Recruiting	`NCT05877716` - EPI-MINN: Targeting Cognition and Motivation - National	N/A
Completed	`NCT01597141` - Psychosis: Early Detection, Intervention and Prevention	N/A
Completed	`NCT00169988` - Antidepressant and Antipsychotic to Treat Attenuated Positive and Negative Symptoms	N/A
Completed	`NCT03447548` - Neurofeedback Training for High Risk Psychosis	N/A
Completed	`NCT06190483` - Investigating the Role of Diazepam on Brain Function and Chemistry in Psychosis Risk	N/A
Completed	`NCT01619319` - Effects of Cognitive Remediation on Cognition in Young People at Clinical High Risk of Psychosis	N/A
Recruiting	`NCT05167396` - REtinal and VIsual Cortical Response in Early PSYchosis	N/A
Terminated	`NCT00169949` - Aripiprazole Treatment of the Prodrome	N/A
Recruiting	`NCT04338152` - Family-Focused Therapy for Individuals at High Clinical Risk for Psychosis: A Confirmatory Efficacy Trial	N/A
Enrolling by invitation	`NCT05532683` - Feasibility Trial of a Lifestyle Intervention for CHR-P	N/A
Enrolling by invitation	`NCT03970005` - Evaluation of Step-Based Care for Individuals at Clinical High Risk for Psychosis

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.