Effects of NAC on Symptoms of CHR Patients

Last updated: February 23, 2024
Sponsor: Centre for Addiction and Mental Health
Overall Status: Active - Recruiting

Phase

N/A

Condition

Tourette's Syndrome

Schizotypal Personality Disorder (Spd)

Mood Disorders

Treatment

N-Acetylcysteine

Placebo

Clinical Study ID

NCT05142735
054-2020
  • Ages 16-35
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. meeting Criteria of Psychosis-Risk Syndromes (COPS) criteria on the StructuredInterview 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 haveundergone a sterilization procedure or have been post-menopausal for at least 1 yearprior to screening OR participant is of child-bearing potential and agrees to use amedically approved method of birth control for the duration of the study

Exclusion

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 fullremission)
  2. concomitant or past neurological condition
  3. visual impairment which is not corrected to normal by prescription glasses history ofreading disability
  4. past antipsychotic treatment at a therapeutic dose
  5. current treatment with a psychotropic medication except antidepressants on which theparticipants 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 intentto 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 Design

Total Participants: 90
Treatment Group(s): 2
Primary Treatment: N-Acetylcysteine
Phase:
Study Start date:
January 13, 2023
Estimated Completion Date:
December 31, 2024

Study 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.

Connect with a study center

  • Centre for Addiction and Mental Health

    Toronto, Ontario M5T 1R8
    Canada

    Active - Recruiting

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