NAC for Schizophrenia

Overseen By Michael Kiang, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Antipsychotics, Antibiotics, Nitroglycerin

Disqualifiers: Neurological condition, Pregnancy, Kidney stones, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether N-acetylcysteine (NAC), an antioxidant, can reduce early symptoms of schizophrenia. Schizophrenia, a mental disorder, can severely affect thinking and behavior. NAC might prevent these issues by managing oxidative stress (damage from free radicals) in the brain. Participants will receive either NAC or a placebo (a harmless pill resembling the real treatment) for eight weeks. The trial seeks individuals showing early warning signs of schizophrenia who have not been diagnosed with another major mental disorder. As an unphased trial, this study offers a unique opportunity to contribute to understanding potential early interventions for schizophrenia.

Will I have to stop taking my current medications?

You may need to stop some medications. If you're on psychotropic medications, you can't participate unless it's an antidepressant you've been taking at a stable dose for at least 30 days. Also, you can't be on antibiotics or nitroglycerin.

Is there any evidence suggesting that N-Acetylcysteine is likely to be safe for humans?

Research has shown that N-acetylcysteine (NAC) might be a safe and well-tolerated option for treating schizophrenia. Studies have found that NAC can improve symptoms in people with schizophrenia when used over time. It acts as an antioxidant, protecting brain cells from damage caused by harmful molecules called free radicals.

In clinical trials, most participants tolerated NAC well, with few side effects reported. This suggests that NAC could also be safe for individuals showing early signs of schizophrenia. However, discussing potential risks and benefits with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

N-Acetylcysteine (NAC) is unique because it offers a different approach to managing schizophrenia compared to traditional antipsychotics like risperidone or clozapine. While most treatments for schizophrenia target dopamine receptors to reduce symptoms, NAC works by enhancing antioxidant levels and reducing oxidative stress in the brain. Researchers are excited about NAC because it has the potential to address the underlying biochemical imbalances in schizophrenia, which could improve symptoms and overall brain health without the typical side effects associated with standard antipsychotic medications.

What evidence suggests that N-Acetylcysteine might be an effective treatment for schizophrenia?

Research has shown that N-acetylcysteine (NAC), which participants in this trial may receive, might help treat schizophrenia by reducing harmful stress in the brain. This stress involves damaging particles called free radicals, and NAC increases a protective substance called glutathione, which neutralizes these particles. A review of studies found that NAC can improve symptoms in people with schizophrenia and early signs of the condition. Additionally, NAC may help protect important brain structures like the fornix, which can be affected in schizophrenia. These findings suggest NAC could be a promising option for people at high risk of developing schizophrenia. ^{1 2 6 7 8}

Who Is on the Research Team?

Michael Kiang, MD, PhD

Principal Investigator

Centre for Addiction and Mental Health

Are You a Good Fit for This Trial?

This trial is for individuals showing early symptoms similar to schizophrenia, known as 'clinical high-risk' (CHR) symptoms. Participants must be able to consent and if female, either not of child-bearing potential or agree to use birth control. Exclusions include visual impairment not corrected by glasses, other DSM-5 diagnoses except some disorders in remission, pregnancy or intent thereof, breastfeeding plans, certain neurological conditions or treatments.

Inclusion Criteria

I have been identified as at risk for psychosis.

I am either not able to have children or will use birth control during the study.

I understand the information given and can make decisions about my health care.

Exclusion Criteria

History of reading disability

I am currently taking nitroglycerin.

I am on a stable dose of antidepressants for over 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either N-Acetylcysteine 2000 mg or placebo daily for 8 weeks

8 weeks

3 visits (in-person) at baseline, week 4, and week 8

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• N-Acetylcysteine

Trial Overview The study tests whether N-Acetylcysteine (NAC), an antioxidant that may help with brain health by reducing oxidative stress, can alleviate CHR symptoms compared to a placebo. The idea is that boosting the body's antioxidants might prevent psychosis in people at risk.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

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

Group II: Placebo Comparator Placebo Group 1 Intervention

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

N-Acetylcysteine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Mucomyst for:

• Mucolytic agent
• Acetaminophen overdose

Approved in European Union as Fluimucil for:

• Mucolytic agent
• Respiratory tract disorders

Approved in Canada as N-Acetylcysteine for:

• Mucolytic agent
• Acetaminophen overdose

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9095537/

The Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of ... Fornix white matter integrity deteriorates in patients with schizophrenia, and NAC supplementation in patients with early psychosis protects fornix white matter ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9673271/

N-Acetylcysteine (NAC) in Schizophrenia Resistant to ... A recent meta-analysis synthesized double-blind placebo-controlled trials of NAC in schizophrenia and first episode psychosis. Seven studies met ...

3. psychiatrist.com psychiatrist.com/jcp/antipsychotic-augmentation-with-n-acetylcysteine-in-schizophrenia/

Antipsychotic Augmentation With N-Acetylcysteine for ... Treated patients with schizophrenia commonly do not recover completely from an episode of psychosis; some continue to experience positive ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0163834324002238

Efficacy of N-acetylcysteine for patients with depression Sepehrmanesh et al. Therapeutic effect of adjunctive N-acetyl cysteine (NAC) on symptoms of chronic schizophrenia: a double-blind, randomized clinical trial ...

5. academic.oup.com academic.oup.com/schizbullopen/article/5/1/sgae005/7615977

N-Acetylcysteine and a Specialized Preventive Intervention for ... ... results for the use of N-acetylcysteine (NAC) in schizophrenia. ... psychosis: results of a randomized trial . J Am Acad Child Adolesc ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0028390825002333

The neuroprotective effects of N-acetylcysteine in ... N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial. Biol. Psychiatry. (2008). M. Berk et al. N ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/pcn.13502

N‐acetylcysteine for schizophrenia: A systematic review ... Yolland reported that the overall symptoms of individuals with schizophrenia improved when they received N-acetylcysteine for 24 weeks or longer.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01885338

N-acetylcysteine (NAC) for Improving Cognitive ... Schizophrenia is a serious mental illness associated with substantial social and occupational dysfunction. While positive psychotic symptoms of schizophrenia ...