Glycine + N-acetylcysteine for Alzheimer's Disease

Overseen By Rajagopal V Sekhar, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Baylor College of Medicine

Must not be taking: Insulin

Disqualifiers: Stroke, Brain tumor, Heart failure, others

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

52 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you use insulin medications.

Is the combination of Glycine and N-acetylcysteine safe for humans?

N-acetylcysteine (NAC) has been studied in patients with Alzheimer's disease and was generally well-tolerated, with no significant side effects reported in the study. However, specific safety data for the combination of Glycine and NAC is not available in the provided research. ^{1 2 3 4 5}

How is the drug Glycine + N-acetylcysteine unique for treating Alzheimer's disease?

Glycine and N-acetylcysteine (NAC) are unique in Alzheimer's treatment because they are not standard drugs for this condition; instead, they are amino acids and antioxidants that may help reduce oxidative stress and inflammation, which are thought to contribute to Alzheimer's disease. This approach is different from traditional treatments that often target enzymes like beta-secretase involved in amyloid plaque formation. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial is testing a supplement called GlyNAC in patients with Alzheimer's disease. The goal is to see if GlyNAC can improve brain function by boosting a natural antioxidant that protects brain cells. Patients are selected based on specific brain scan results and cognitive tests.

Research Team

Rajagopal V Sekhar, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for people aged 55-85 with Alzheimer's, showing memory loss for over a year and confirmed Tau protein in the brain. They need someone to support them during the study. Excluded are those recently hospitalized, with diabetes, untreated thyroid or liver disease, severe kidney issues, anemia, history of stroke or active heart failure/cancer (except certain skin cancers), and untreated severe psychiatric conditions.

Inclusion Criteria

Availability of a study partner

I have been experiencing worsening memory loss for over a year and scored 10-20 on a cognitive test.

I am between 55 and 85 years old.

Exclusion Criteria

I have been hospitalized within the last 3 months.

Your hemoglobin level is less than 11.0 grams per deciliter.

Pregnancy or nursing (unlikely in this population)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo imaging studies (MRI, FDG-PET and TSPO-PET scans) and cognitive, metabolic, and mitochondrial measurements before supplementation

1-2 weeks

1 visit (in-person)

Treatment

Participants receive GlyNAC or alanine placebo supplementation for 24 weeks, with cognitive and metabolic assessments at 12 and 24 weeks

24 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including repeated FDG- and TSPO-PET scans

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Alanine
• Glycine
• N-acetylcysteine

Trial Overview The trial tests if adding glycine and N-acetylcysteine supplements can improve brain metabolism and reduce inflammation compared to alanine (placebo) in Alzheimer's patients. It will also look at how these supplements affect cognitive functions.

Participant Groups

Group I: Glycine plus N-acetylcysteine Experimental Treatment 2 Interventions

Glycine and cysteine are amino-acid (protein) precursors of glutathione. Cysteine is provided as N-acetylcysteine

Group II: Alanine Placebo Group 1 Intervention

Alanine is an amino-acid (protein), and not a precursor of glutathione synthesis

Glycine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Glycine for:

• Dietary supplement
• Pharmaceutical ingredient

Approved in European Union as Glycine for:

• Food additive
• Pharmaceutical excipient

Approved in Canada as Glycine for:

• Natural health product
• Pharmaceutical ingredient

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 study of 40 elderly patients with mild-to-moderate Alzheimer-type disorders, selegiline (10 mg daily) showed significant improvements in cognitive functions such as information processing, verbal fluency, and visuospatial abilities over 90 days, outperforming L-acetylcarnitine (500 mg twice daily).

Both selegiline and L-acetylcarnitine were well-tolerated, with no significant adverse effects or abnormalities detected in laboratory tests, indicating a good safety profile for both treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selegiline versus L-acetylcarnitine in the treatment of Alzheimer-type dementia. Campi, N., Todeschini, GP., Scarzella, L.[2015]

In a one-year pilot trial involving 15 Alzheimer patients, vinpocetine at doses of 30, 45, and 60 mg per day did not show any improvement in cognitive function or overall patient functioning compared to a matched control group.

Despite the lack of efficacy, vinpocetine was well-tolerated with no significant side effects reported, leading to the conclusion that it does not slow cognitive decline in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and lack of efficacy of vinpocetine in Alzheimer's disease. Thal, LJ., Salmon, DP., Lasker, B., et al.[2019]

In a 24-week study involving 433 newly diagnosed Alzheimer's patients, the rivastigmine transdermal patch was found to be safe and tolerable, with only 2.54% experiencing serious adverse events.

Efficacy was demonstrated by a significant improvement in Mini-Mental State Examination scores, increasing from a median of 21.0 to 22.0 after 6 months, indicating potential cognitive benefits from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of rivastigmine transdermal patch formulation in newly diagnosed patients with Alzheimer's dementia in naturalistic conditions. Pregelj, P.[2015]

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 an 11-week study involving 181 patients with mild to moderate Alzheimer's disease, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid modulator LY451395 did not show significant improvement in cognitive function compared to placebo, as measured by the ADAS-Cog scale.

While there were some marginal improvements in neuropsychiatric symptoms after 8 weeks of treatment, the overall safety profile was similar between LY451395 and placebo, with most adverse events being mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. Chappell, AS., Gonzales, C., Williams, J., et al.[2022]

Research indicates that levels of N-acetylaspartyl glutamate (NAAG) are significantly reduced in the brains of patients with Alzheimer's disease, which is linked to cognitive impairment.

Attempts to use mouse models of Alzheimer's to study NAAG restoration through GCPII inhibition revealed discrepancies between human and mouse brain NAAG levels, suggesting that current mouse models may not accurately predict human disease outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The NAAG'ing Concerns of Modeling Human Alzheimer's Disease in Mice. Hollinger, KR., Alt, J., Rais, R., et al.[2021]

BACE (beta-site APP-cleaving enzyme) is crucial in the formation of amyloid plaques in Alzheimer's disease by cleaving the amyloid precursor protein (APP), making it a key target for potential treatments.

The study reveals specific interactions between BACE and its substrate APP, particularly the importance of certain residues that could guide the development of inhibitors to effectively block BACE activity and potentially prevent Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modeling of substrate specificity of the Alzheimer's disease amyloid precursor protein beta-secretase. Sauder, JM., Arthur, JW., Dunbrack, RL.[2013]

A new method for extracting and purifying amyloid beta-protein (A beta) from Alzheimer's disease brains revealed that A beta 1-40 is the predominant form found in the cerebral cortex of five examined cases.

The study suggests that A beta 1-40 and A beta 1-43 may originate from different processes involving beta-amyloid precursor protein, highlighting the importance of using synthetic A beta 1-40 for future research on amyloid-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mass spectrometry of purified amyloid beta protein in Alzheimer's disease. Mori, H., Takio, K., Ogawara, M., et al.[2021]

Researchers have identified and characterized a new protease called BACE, which is responsible for the cleavage of amyloid precursor protein (APP) and is a key player in the production of amyloid beta peptide, a hallmark of Alzheimer's disease.

Inhibition of BACE through antisense technology reduced the production of beta-secretase cleavage products, suggesting that targeting BACE could be a promising therapeutic strategy for treating Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Vassar, R., Bennett, BD., Babu-Khan, S., et al.[2022]

The study developed improved high-throughput screening assays for BACE-1 inhibitors using casein-FITC and L-BAPNA as substrates, which showed greater efficiency and sensitivity compared to previous methods.

Donepezil, a known acetylcholinesterase inhibitor, was identified as a potent BACE-1 inhibitor with a submicromolar potency of 170 nM, suggesting its potential dual role in treating Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiwell fluorometric and colorimetric microassays for the evaluation of beta-secretase (BACE-1) inhibitors. Mancini, F., Naldi, M., Cavrini, V., et al.[2016]

References

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

Selegiline versus L-acetylcarnitine in the treatment of Alzheimer-type dementia. [2015]

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

The safety and lack of efficacy of vinpocetine in Alzheimer's disease. [2019]

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

Safety and tolerability of rivastigmine transdermal patch formulation in newly diagnosed patients with Alzheimer's dementia in naturalistic conditions. [2015]

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

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

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

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

The NAAG'ing Concerns of Modeling Human Alzheimer's Disease in Mice. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Modeling of substrate specificity of the Alzheimer's disease amyloid precursor protein beta-secretase. [2013]

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

Mass spectrometry of purified amyloid beta protein in Alzheimer's disease. [2021]

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

Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Multiwell fluorometric and colorimetric microassays for the evaluation of beta-secretase (BACE-1) inhibitors. [2016]