Glutathione Precursors for Mild Cognitive Impairment

Overseen By Rajagopal V Sekhar, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Baylor College of Medicine

Disqualifiers: Diabetes, Liver disease, Stroke, others

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Elderly humans have an increased risk of dementia which begins as mild defects in memory called mild cognitive impairment. Glutathione (GSH), a key endogenous antioxidant has been linked to cognition. This exploratory study will investigate mechanisms linked to GSH for cognitive impairment (and improvement) by studying humans with mild cognitive impairment who will be evaluated 12-weeks after receiving either N-acetylcysteine and glycine (GSH precursors), or receiving alanine, and a further 12-weeks after stopping these supplements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment N-acetylcysteine plus Glycine for mild cognitive impairment?

Research suggests that N-acetylcysteine, a component of the treatment, may help increase levels of glutathione, an important antioxidant that declines in Alzheimer's disease and mild cognitive impairment. This could potentially reduce oxidative stress and improve cognitive function, although more direct evidence is needed. ^{1 2 3 4 5}

Is N-acetylcysteine safe for humans?

N-acetylcysteine (NAC) is generally considered safe for human use and is available as a dietary supplement. It has been studied for its potential benefits in cognitive health and Alzheimer's disease, with no major safety concerns reported in the research. ^{1 6 7 8 9}

How is the drug N-acetylcysteine plus Glycine unique for treating mild cognitive impairment?

This drug is unique because it aims to boost glutathione levels, a key antioxidant that may be reduced in people with mild cognitive impairment, potentially helping to protect the brain from oxidative stress and slow cognitive decline. ^{2 3 4 10 11}

Eligibility Criteria

This trial is for older adults with mild cognitive impairment, which is an early stage of memory loss. Participants should not have been hospitalized recently, have diabetes, severe kidney or liver disease, a history of stroke or heart issues, or untreated depression.

Inclusion Criteria

I have been diagnosed with Mild Cognitive Impairment.

Exclusion Criteria

I have liver disease or my liver tests are high.

You have a history of mental health disorders.

Hemoglobin concentration less than 11 g/dL

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive either N-acetylcysteine and glycine or alanine for 12 weeks

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

1 visit (in-person)

Treatment Details

Interventions

• Alanine
• Glycine
• N-acetylcysteine
• N-acetylcysteine plus Glycine

Trial Overview The study explores if taking supplements N-acetylcysteine and glycine can improve cognition by increasing antioxidant levels in the brain. Participants will be compared to those taking alanine over a period of 12 weeks and then observed for another 12 weeks after stopping the supplements.

Participant Groups

Group I: MCI-active Active Control 2 Interventions

30 Subjects with MCI will receive N-acetylcysteine and glycine for 12-weeks. ll subjects will be studied at baseline prior to supplementation, after completing 12-weeks of supplementation, and 12-weeks after stopping supplementation (i.e. at 24-weeks). Supplements are only provided for first 12-weeks.

Group II: MCI-placebo Placebo Group 1 Intervention

30 subjects will received alanine for 12-weeks. All subjects will be studied at baseline prior to supplementation, after completing 12-weeks of supplementation, and 12-weeks after stopping supplementation (i.e. at 24-weeks). Supplements are only provided for first 12-weeks

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

Approved in United States as N-acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Approved in European Union as N-acetylcysteine for:

• Paracetamol overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

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 30-week multicenter trial involving 415 patients with mild to moderate Alzheimer's disease, tacrine hydrochloride was found to significantly improve or stabilize cognitive and noncognitive symptoms compared to a placebo, particularly in areas like memory and mood.

The study suggests that tacrine's effects on specific cognitive and noncognitive deficits can be better evaluated by focusing on individual assessment items from the Alzheimer's Disease Assessment Scale (ADAS), enhancing the understanding of its therapeutic impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tacrine on language, praxis, and noncognitive behavioral problems in Alzheimer disease. Raskind, MA., Sadowsky, CH., Sigmund, WR., et al.[2019]

Alzheimer's disease (AD) has many underlying biochemical pathways, making it challenging for single drugs to be effective; however, targeting amnestic mild cognitive impairment (aMCI) may require addressing fewer pathways, potentially allowing for more effective treatments.

Eight drugs have been identified that target various pathways related to both MCI and AD, and combinations of these drugs could offer a promising approach to prevent the progression from aMCI to AD, warranting further clinical trials to test their safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of Alzheimer's disease by treating mild cognitive impairment with combinations chosen from eight available drugs. Fessel, J.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Plasma Glutathione Levels Decreased with Cognitive Decline among People with Mild Cognitive Impairment (MCI): A Two-Year Prospective Study. [2021]

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

Brain glutathione levels--a novel biomarker for mild cognitive impairment and Alzheimer's disease. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Supplementation with γ-glutamylcysteine (γ-GC) lessens oxidative stress, brain inflammation and amyloid pathology and improves spatial memory in a murine model of AD. [2021]

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

Oxidative stress in blood in Alzheimer's disease and mild cognitive impairment: a meta-analysis. [2022]

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

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

7. Ireland pubmed.ncbi.nlm.nih.gov

N-acetylcysteine treatment attenuates the cognitive impairment and synaptic plasticity loss induced by streptozotocin. [2022]

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

Effect of tacrine on language, praxis, and noncognitive behavioral problems in Alzheimer disease. [2019]

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

Prevention of Alzheimer's disease by treating mild cognitive impairment with combinations chosen from eight available drugs. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Altered central and blood glutathione in Alzheimer's disease and mild cognitive impairment: a meta-analysis. [2022]

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

Do glutathione levels decline in aging human brain? [2016]