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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how certain supplements might help people with mild cognitive impairment (MCI), which involves memory problems that could lead to dementia. The trial tests two supplements: N-acetylcysteine and glycine, believed to boost a brain antioxidant, and compares them to a placebo (a harmless pill with no active ingredients). Participants will take the supplements for 12 weeks, after which researchers will evaluate changes in memory and cognition. People diagnosed with mild cognitive impairment who haven't had recent hospital visits or certain medical conditions might be a good fit for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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.

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

Research has shown that GlyNAC, a mix of glycine and N-acetylcysteine (NAC), is generally safe. In past studies, older adults who took GlyNAC for 24 weeks did not report major problems. This supplement also reduced cell damage and enhanced the body's natural defenses. NAC, one of its components, is known for its safety, with issues being rare unless taken in very high amounts or unusual ways.

While specific safety data for the exact mix of GlyNAC is lacking, studies suggest it is safe. Participants in clinical trials have used it without serious side effects, indicating it could be a safe choice for those considering joining a trial. ^{1 2 3 4 5}

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

Researchers are excited about N-acetylcysteine and glycine for mild cognitive impairment because these compounds work by boosting glutathione levels, a powerful antioxidant that protects brain cells. Unlike other treatments that primarily focus on neurotransmitter levels or amyloid plaques, this approach directly enhances the brain's natural defense system. By potentially reducing oxidative stress, these treatments might slow cognitive decline more effectively, offering a novel pathway that differs from current options like cholinesterase inhibitors or NMDA receptor antagonists. This fresh mechanism of action gives hope for better management of mild cognitive impairment.

What evidence suggests that this trial's treatments could be effective for mild cognitive impairment?

Research shows that GlyNAC, a mix of N-acetylcysteine and glycine, might improve brain health in older adults. In this trial, some participants will receive GlyNAC, while others will receive a placebo. Studies have found that GlyNAC can reduce damage from free radicals, correct a shortage of an important antioxidant in the body, and boost energy production in cells. One study showed that older adults who took GlyNAC for 24 weeks became stronger and improved their memory and thinking skills. Additionally, N-acetylcysteine alone has been linked to better thinking abilities and less damage from free radicals. These findings suggest that GlyNAC could help people with mild memory problems, possibly slowing age-related memory issues. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10215265/

GlyNAC (Glycine and N-Acetylcysteine) Supplementation in ... GlyNAC supplementation improved/corrected the brain defects and reversed ACD. This study finds that naturally-occurring ACD is associated with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8002905/

Glycine and N‐acetylcysteine (GlyNAC) supplementation in ... GlyNAC supplementation for 24‐weeks in OA was well tolerated and lowered OxS, corrected intracellular GSH deficiency and mitochondrial dysfunction.

3. bcm.edu bcm.edu/news/glynac-improves-strength-and-cognition-in-older-humans

GlyNAC improves strength and cognition in older humans The results of this study show that older humans taking GlyNAC for 24 weeks saw improvements in many characteristic defects of aging.

4. mdpi.com mdpi.com/2076-3425/15/2/164

Effect of N-Acetyl Cysteine as an Adjuvant Treatment in ... The results obtained showed that NAC supplementation produced improved cognitive performance, decreased levels of oxidative stress markers, lowered activities ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0022316622004552

GlyNAC Supplementation Improves Glutathione Deficiency ... GlyNAC supplementation could be a novel nutritional approach to improve age-associated defects and promote healthy aging.

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002%2Fctm2.372

Glycine and N‐acetylcysteine (GlyNAC) supplementation ... GlyNAC supplementation for 24-weeks in OA was well tolerated and lowered OxS, corrected intracellular GSH deficiency and mitochondrial ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8234027/

N-Acetylcysteine (NAC): Impacts on Human Health - PMC It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant ...

8. withpower.com withpower.com/trial/early-phase-1-alzheimer-disease-6-2021-90905

Glycine + N-acetylcysteine for Alzheimer's Disease However, specific safety data for the combination of Glycine and NAC is not available in the provided research. Show more.