Effects of NAC on Symptoms of CHR Patients

NCT05142735 | Recruiting DMC

• 1 other identifier: 054-2020
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prodromal Schizophrenia

Keywords

psychosis; schizophrenia; N-acetylcysteine; prodrome; mismatch negativity; event-related potentials; clinical high risk state

Outcome Measures

Primary Outcomes (1)

• Change in positive psychosis-like symptoms from baseline to 8 weeks

  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 Outcomes (2)

• Change in mismatch negativity (MMN) amplitude from baseline to 8 weeks

  Week 0 to week 8

• Change in N400 semantic priming effect from baseline to 8 weeks

  Week 0 to week 8

Study Arms (2)

Experimental

EXPERIMENTAL

N-Acetylcysteine 2000 mg (4 x 500-mg tablets) orally every morning for 8 weeks

Dietary Supplement: N-Acetylcysteine

Placebo Comparator

PLACEBO COMPARATOR

N-Acetylcysteine Placebo tablet matching N-Acetylcysteine orally every morning for 8 weeks

Dietary Supplement: Placebo

Interventions

N-Acetylcysteine DIETARY_SUPPLEMENT

2000 mg (4 x 500-mg tablets) every morning

Also known as: NAC

Experimental

Placebo DIETARY_SUPPLEMENT

4 placebo tablets every morning

Placebo Comparator

Eligibility Criteria

• Age: 16 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• meeting Criteria of Psychosis-Risk Syndromes (COPS) criteria on the Structured Interview for Psychosis-Risk Syndromes (SIPS)
• capacity to provide informed consent
• 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

You may not qualify if:

• 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)
• concomitant or past neurological condition
• visual impairment which is not corrected to normal by prescription glasses history of reading disability
• past antipsychotic treatment at a therapeutic dose
• current treatment with a psychotropic medication except antidepressants on which the participants has been on a stable dose for at least 30 days.
• pregnancy (as identified on self-report and/or rapid urine pregnancy test) or intent to become pregnant according to self-report
• breastfeeding or plan to do so
• history of kidney stones
• current treatment with an antibiotic
• current treatment with nitroglycerin
• allergy to any ingredients in either the investigational product or placebo product

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

RECRUITING

Related Publications (19)

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MeSH Terms

Conditions

Schizotypal Personality Disorder; Psychotic Disorders; Schizophrenia

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Personality Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Michael Kiang, MD, PhD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Kiang, MD, PhD

CONTACT

416-535-8501; michael.kiang@camh.ca

Jenny Lepock, PhD

CONTACT

416-535-8501; jenny.lepock@camh.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, investigators and research staff are blinded to the conditions. Research Pharmacy staff are unblinded and responsible for randomization and NAC or placebo dispensing.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are assigned to one of NAC or placebo groups in parallel for the duration of the study. This will be a randomized, double-blind, placebo-controlled trial. Participants will be randomized to take either NAC 2000 mg or placebo, in the form of oral capsules, every morning for 8 weeks.

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: December 3, 2021
• Study Start: January 13, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)