Effects of NAC on Symptoms of CHR Patients

February 23, 2024 updated by: Centre for Addiction and Mental Health

Effects of N-acetylcysteine on Psychosis-like Symptoms and a Neurophysiological Biomarker of the Clinical High Risk for Schizophrenia

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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 Type

Interventional

Enrollment (Estimated)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 35 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. meeting Criteria of Psychosis-Risk Syndromes (COPS) criteria on the Structured Interview for Psychosis-Risk Syndromes (SIPS)
  2. capacity to provide informed consent
  3. if female, participant is not of child-bearing potential, defined as females who have undergone a sterilization procedure or have been post-menopausal for at least 1 year prior to screening OR participant is of child-bearing potential and agrees to use a medically approved method of birth control for the duration of the study

Exclusion Criteria:

  1. meeting criteria for any other DSM-5 diagnosis at the time of the study (except -personality disorder, nicotine use disorder, or other substance use disorder in full remission)
  2. concomitant or past neurological condition
  3. visual impairment which is not corrected to normal by prescription glasses history of reading disability
  4. past antipsychotic treatment at a therapeutic dose
  5. current treatment with a psychotropic medication except antidepressants on which the participants has been on a stable dose for at least 30 days.
  6. pregnancy (as identified on self-report and/or rapid urine pregnancy test) or intent to become pregnant according to self-report
  7. breastfeeding or plan to do so
  8. history of kidney stones
  9. current treatment with an antibiotic
  10. current treatment with nitroglycerin
  11. allergy to any ingredients in either the investigational product or placebo product

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental
N-Acetylcysteine 2000 mg (4 x 500-mg tablets) orally every morning for 8 weeks
Dietary supplement: N-Acetylcysteine
2000 mg (4 x 500-mg tablets) every morning
Other Names:
  • NAC
Placebo Comparator: Placebo Comparator
N-Acetylcysteine Placebo tablet matching N-Acetylcysteine orally every morning for 8 weeks
Dietary supplement: Placebo
4 placebo tablets every morning

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in positive psychosis-like symptoms from baseline to 8 weeks
Time Frame: Week 0 to week 8
Measured by the Positive symptom score of the Scale of Psychosis-Risk Symptoms, where the minimum score is 0 and the maximum score is 30, and higher scores mean a worse outcome.
Week 0 to week 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in mismatch negativity (MMN) amplitude from baseline to 8 weeks
Time Frame: Week 0 to week 8
MMN amplitude will be measured as mean voltage from 135-205 ms post-stimulus onset of the ERP waveform formed by subtracting the average for standard tones from the average for deviant tones.
Week 0 to week 8
Change in N400 semantic priming effect from baseline to 8 weeks
Time Frame: Week 0 to week 8
N400 semantic priming effect will be measured as mean voltage from 300-500 ms post-stimulus onset of the ERP waveform formed by subtracting the average for related stimuli from the average for unrelated stimuli.
Week 0 to week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre for Addiction and Mental Health

Investigators

  • Principal Investigator: Michael Kiang, MD, PhD, Centre for Addiction and Mental Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 13, 2023

Primary Completion (Estimated)

November 1, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

November 19, 2021

First Submitted That Met QC Criteria

December 1, 2021

First Posted (Actual)

December 3, 2021

Study Record Updates

Last Update Posted (Actual)

February 26, 2024

Last Update Submitted That Met QC Criteria

February 23, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 054-2020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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