N Acetylcysteine for Cognitive Impairment

Overseen By Krista L Lanctôt, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Nitroglycerin

Disqualifiers: Stroke, Epilepsy, Asthma, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well an add-on treatment called N-acetylcysteine (NAC) can improve cognitive function in people with vascular cognitive impairment who are also in a cardiac rehabilitation program. Participants will take either NAC or a placebo (a pill with no active ingredient) for 24 weeks to determine if NAC aids memory and thinking skills. The trial targets individuals in the University Health Network Toronto Rehabilitation Institute's cardiac rehab program who have noticed some memory or thinking difficulties but do not have full-blown dementia. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you use daily Nitroglycerin, you cannot participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that N-acetylcysteine (NAC) is generally safe. Studies have found that most people tolerate it well, even with long-term use. In past research, participants using NAC did not experience serious side effects. Some mild side effects have been reported, but these are rare and often depend on the method of administration or very high doses.

For instance, studies involving older adults and those with mild memory problems found NAC to be well-tolerated, with no serious issues reported. In another study, NAC proved safe and did not cause lasting problems, although a few participants experienced minor issues. Overall, NAC's safety makes it a promising option for supporting brain health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cognitive impairment?

Most treatments for cognitive impairment focus on managing symptoms or slowing progression through drugs like cholinesterase inhibitors and memantine. But N-acetylcysteine (NAC) works differently, targeting oxidative stress and inflammation, which are believed to contribute to cognitive decline. Researchers are excited about NAC because it could offer a new way to protect and support brain health, potentially improving cognitive function more effectively than current options. Additionally, NAC is known for its antioxidant properties and has been used safely in other medical contexts, which adds to the optimism about its potential benefits for cognitive impairment.

What evidence suggests that N Acetylcysteine might be an effective treatment for cognitive impairment?

This trial will compare N-acetylcysteine (NAC) with a placebo to assess its effects on cognitive impairment. Studies have shown that NAC can improve thinking and memory. Research indicates that NAC reduces memory problems and protects against memory loss. Other studies suggest NAC may enhance brain function and slow memory decline, especially with aging or certain conditions. NAC increases antioxidants in the brain, protecting brain cells from damage. Early findings suggest it may also improve performance on memory tests. Overall, promising evidence supports NAC's role in promoting brain health. ^{1 6 7 8 9}

Who Is on the Research Team?

Krista L Lanctôt, PhD

Principal Investigator

Sunnybrook Research Institute

Are You a Good Fit for This Trial?

Inclusion Criteria

Males or females aged 55-80 years.

Speaks and understands English.

Modest deficits (1 SD below population norm) in executive function, memory, processing speed, or working memory based on the 60-minute battery recommended by the NINDS-CSN.

Exclusion Criteria

You have had a stroke in the past.

You have extremely high or low blood pressure, as determined by a doctor.

You have a current neurological condition such as Parkinson's disease, multiple sclerosis, or significant traumatic brain injury.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral NAC supplementation as an add-on therapy to improve cognitive function, with dosage increasing weekly until reaching 2,400 mg/day, alongside a cardiac rehabilitation program

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• N Acetylcysteine
• Placebo oral capsule

How Is the Trial Designed?

Group I: N-acetylcysteine Active Control 1 Intervention

Participants randomized into the N-acetylcysteine arm will be receiving N-acetylcysteine for 24 weeks.

Group II: Placebo Placebo Group 1 Intervention

Participants randomized into the placebo arm will be receiving placebo for 24 weeks.

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

N-Acetylcysteine (NAC) effectively prevents sensory neuronal loss after peripheral nerve transection in a dose-dependent manner, with significant protection observed at doses of 10 mg/kg/day and above.

The study, using a rat model, indicates that higher doses (150 and 300 mg/kg/day) completely prevent neuronal loss, suggesting NAC has a wide therapeutic range and potential for clinical use in nerve injury recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the dose-response of N-acetylcysteine in the prevention of sensory neuronal loss after peripheral nerve injury. West, CA., Hart, AM., Terenghi, G., et al.[2019]

In a study of 162 patients with age-associated memory impairment, a combination of piracetam (4.8 g) and cognitive therapy showed the most significant improvement in memory, particularly in those with the lowest baseline performance.

The optimal results were achieved when cognitive training sessions started after 6 weeks of piracetam treatment, indicating a potential timing effect in the intervention's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug therapy and memory training programs: a double-blind randomized trial of general practice patients with age-associated memory impairment. Israel, L., Melac, M., Milinkevitch, D., et al.[2019]

In a double-blind study involving patients with probable Alzheimer's disease, N-acetylcysteine (NAC) was administered and showed favorable effects on cognitive outcomes compared to placebo after 3 and 6 months of treatment.

While NAC treatment improved nearly all measured outcomes, significant differences were only observed in a subset of cognitive tasks, suggesting potential benefits that may vary across different cognitive functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease. Adair, JC., Knoefel, JE., Morgan, N.[2019]

In a review of placebo group data from multiple trials for mild cognitive impairment (MCI), significant variability in performance was observed, with NIA trials showing expected cognitive decline while industry-sponsored trials often reported stable or improved performance.

The presence of the APOE4 gene variant influenced cognitive outcomes, indicating that genetic factors may play a role in how participants respond in MCI trials, despite similar diagnostic criteria being used across studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized controlled trials in mild cognitive impairment: Sources of variability. Petersen, RC., Thomas, RG., Aisen, PS., et al.[2022]

N-Acetylcysteine is effective as a mucolytic agent for chronic bronchitis and as an antidote for paracetamol poisoning, with peak plasma concentrations achieved within 1 to 2 hours after oral doses of 200 to 400 mg.

While it has significant therapeutic benefits, common side effects include nausea, vomiting, and diarrhea, and it may interact with other drugs, particularly paracetamol and certain anticancer agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of N-acetylcysteine. Holdiness, MR.[2022]

A study of 10 over-the-counter dietary supplements marketed for memory enhancement found that they contained unapproved drugs like omberacetam and aniracetam, with some products exposing consumers to pharmaceutical-level dosages.

Many of these supplements had inaccurate labeling, with 75% of declared drug quantities being incorrect, raising concerns about the safety and health effects of consuming untested combinations of unapproved drugs without medical supervision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five Unapproved Drugs Found in Cognitive Enhancement Supplements. Cohen, PA., Avula, B., Wang, YH., et al.[2022]

Pharmacological cognitive enhancement (CE) involves the use of various psychoactive substances, including over-the-counter drugs like caffeine, prescription medications for ADHD, and illicit drugs, but evidence shows these substances have limited cognitive benefits and pose significant safety risks.

Prevalence rates of CE drug use among healthy individuals vary widely, from less than 1% to over 20%, influenced by factors such as the population surveyed and the definitions of CE, highlighting the need for better data to inform healthcare policies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Substances used and prevalence rates of pharmacological cognitive enhancement among healthy subjects. Franke, AG., Bagusat, C., Rust, S., et al.[2014]

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N-acetylcysteine

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N-acetylcysteine (NAC), a well-known antioxidant, could attenuate cognitive behavioral impairments and neuroinflammatory damage by restoring ...

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N-Acetylcysteine for Hereditary Cystatin C Amyloid ...

NAC was safe and well tolerated; a total of 5 cerebrovascular bleeds occurred during the study without permanent neurological sequela. Meaning ...