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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if taking an NAC supplement can help improve brain function in patients with mild cognitive issues who are also in a heart rehab program. NAC works by protecting brain cells from damage. N-acetylcysteine (NAC) has been studied for its potential benefits in various conditions, including brain injury, cognitive impairment, and oxidative stress.

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.

What evidence supports the effectiveness of the drug N Acetylcysteine for cognitive impairment?

Research on N-acetylcysteine (NAC) for Alzheimer's disease showed that it helped improve some cognitive tasks, suggesting it might be beneficial for cognitive impairment. Additionally, studies on other cognition enhancers like piracetam have shown improvements in memory, which might indicate potential benefits of similar treatments. ^{1 2 3 4 5}

Is N-acetylcysteine safe for human use?

N-acetylcysteine (NAC) has been studied in patients with Alzheimer's disease and is generally considered safe, with no significant safety concerns reported in the study. ^{1 6 7 8 9}

How does the drug N-acetylcysteine differ from other treatments for cognitive impairment?

N-acetylcysteine is unique because it may help increase levels of glutathione, an important antioxidant, which could reduce oxidative stress linked to cognitive decline. Unlike other treatments, it is also available as a dietary supplement and has potential neuroprotective benefits, although its low bioavailability is a challenge. ^{10 11 12 13 14}

Research Team

Krista L Lanctôt, PhD

Principal Investigator

Sunnybrook Research Institute

Eligibility Criteria

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

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

Treatment Details

Interventions

• N Acetylcysteine
• Placebo oral capsule

Participant Groups

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+

Findings from Research

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 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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease. [2019]

2. England 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. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Expectancy effect: impact of pill administration on cognitive performance in healthy seniors. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and clinical relevance of cognition enhancers. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Randomized controlled trials in mild cognitive impairment: Sources of variability. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Five Unapproved Drugs Found in Cognitive Enhancement Supplements. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Substances used and prevalence rates of pharmacological cognitive enhancement among healthy subjects. [2014]

8. England pubmed.ncbi.nlm.nih.gov

Oral intake of carboxy alkyl ester improves attention: A randomized double-blind cross-over placebo-controlled study. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

The Use and Impact of Cognitive Enhancers among University Students: A Systematic Review. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of N-acetylcysteine. [2022]

11. Austria pubmed.ncbi.nlm.nih.gov

Analysis of the dose-response of N-acetylcysteine in the prevention of sensory neuronal loss after peripheral nerve injury. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Dose dependent pharmacokinetics of N-acetylcysteine after oral dosing to man. [2019]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of the Neuroprotective Potential of N-Acetylcysteine for Prevention and Treatment of Cognitive Aging and Dementia. [2018]

14. United States pubmed.ncbi.nlm.nih.gov

Intravenous Administration of Stable-Labeled N-Acetylcysteine Demonstrates an Indirect Mechanism for Boosting Glutathione and Improving Redox Status. [2015]