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Effects of NAC on Symptoms of CHR Patients

Primary Purpose

Prodromal Schizophrenia

Status

Recruiting

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

N-Acetylcysteine

Placebo

About this trial

This is an interventional treatment trial for Prodromal Schizophrenia focused on measuring psychosis, schizophrenia, N-acetylcysteine, prodrome, mismatch negativity, event-related potentials, clinical high risk state

Eligibility Criteria

16 Years - 35 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
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

Sites / Locations

Centre for Addiction and Mental HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental

Placebo Comparator

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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.

Change in N400 semantic priming effect from baseline to 8 weeks

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.

Full Information

NCT ID

NCT05142735

First Posted

November 19, 2021

Last Updated

August 29, 2023

Sponsor

Centre for Addiction and Mental Health

1. Study Identification

Unique Protocol Identification Number

NCT05142735

Brief Title

Effects of NAC on Symptoms of CHR Patients

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 13, 2023 (Actual)

Primary Completion Date

November 1, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre for Addiction and Mental Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prodromal Schizophrenia

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

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.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Participants, investigators and research staff are blinded to the conditions. Research Pharmacy staff are unblinded and responsible for randomization and NAC or placebo dispensing.

Allocation

Randomized

Enrollment

90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo Comparator

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Dietary Supplement

Intervention Name(s)

N-Acetylcysteine

Other Intervention Name(s)

NAC

Intervention Description

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

Intervention Type

Dietary Supplement

Intervention Name(s)

Placebo

Intervention Description

4 placebo tablets every morning

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

Week 0 to week 8

Secondary Outcome Measure Information:

Title

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

Description

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.

Time Frame

Week 0 to week 8

Title

Change in N400 semantic priming effect from baseline to 8 weeks

Description

Time Frame

Week 0 to week 8

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Maximum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Michael Kiang, MD, PhD

Phone

416-535-8501

Ext

30337

michael.kiang@camh.ca

First Name & Middle Initial & Last Name or Official Title & Degree

Jenny Lepock, PhD

Phone

416-535-8501

Ext

34639

jenny.lepock@camh.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Kiang, MD, PhD

Organizational Affiliation

Centre for Addiction and Mental Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre for Addiction and Mental Health

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5T 1R8

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jenny Lepock, PhD

Phone

4167026423

jenny.lepock@camh.ca

First Name & Middle Initial & Last Name & Degree

Michael Kiang

michael.kiang@camh.ca

12. IPD Sharing Statement

Plan to Share IPD

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Effects of NAC on Symptoms of CHR Patients

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