Glycine + N-acetylcysteine for Alzheimer's Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Baylor College of Medicine
Must not be taking: Insulin
Disqualifiers: Stroke, Brain tumor, Heart failure, others
Trial Summary
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.
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.
12345How 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.
678910Eligibility 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.
+1 more
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)
+6 more
Trial 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)
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Glycine plus N-acetylcysteineExperimental Treatment2 Interventions
Glycine and cysteine are amino-acid (protein) precursors of glutathione. Cysteine is provided as N-acetylcysteine
Group II: AlaninePlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Baylor College of MedicineHouston, TX
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Who Is Running the Clinical Trial?
Baylor College of MedicineLead Sponsor
The Methodist Hospital Research InstituteCollaborator
References
Selegiline versus L-acetylcarnitine in the treatment of Alzheimer-type dementia. [2015]Forty elderly patients (13 men and 27 women, aged 56 to 80 years) were enrolled in a single-blind, randomized, parallel study to assess the efficacy and safety of selegiline (10 mg, once daily) and that of L-acetylcarnitine (500 mg, twice daily) in the treatment of patients with mild-to-moderate Alzheimer-type disorders. The treatments lasted 90 days, after a run-in period of 15 days. An extensive psychometric examination, carried out at baseline and subsequently at every 30 days of treatment, was used for evaluation of efficacy. Drug safety was assessed by noting any adverse effects that occurred during treatment and by performing laboratory tests at the beginning and end of treatment. According to the resulting data, selegiline therapy led to a global improvement in the capacity for the processing, storage, and retrieval of given information. Improvements in verbal fluency and visuospatial abilities were also noted. The marked between-group differences demonstrate that, at the dosage used, selegiline was far more effective than L-acetylcarnitine with respect to the degree of improvement. Finally, tolerability of both drugs was excellent, inasmuch as neither the monitoring for adverse drug reactions nor laboratory tests revealed any abnormalities resulting from therapy.
The safety and lack of efficacy of vinpocetine in Alzheimer's disease. [2019]Fifteen Alzheimer patients were treated with increasing doses of vinpocetine (30, 45, and 60 mg per day) in an open-label pilot trial during a one-year period. Patients were assessed seven times both on and off drug with: the Buschke Selective Reminding Task, a letter fluency test, a category fluency test, the Boston Naming Test, a cognitive capacity screening examination, and a clinical global impression. Vinpocetine failed to improve cognition on psychometric testing or overall functioning, as measured by the clinical global impression, at any dose tested. Patients showed significant decline in most measures during the course of the study, at the same rate as a matched control group, consistent with progressive dementia. There were no significant side effects from drug therapy. We conclude that vinpocetine is ineffective in improving cognitive deficits and does not slow the rate of decline in individuals with Alzheimer's disease.
Safety and tolerability of rivastigmine transdermal patch formulation in newly diagnosed patients with Alzheimer's dementia in naturalistic conditions. [2015]The majority of available data on safety and tolerability issues regarding cholinesterase inhibitors used for the treatment of Alzheimer's disease has been available for orally administered formulations. The objective of this prospective, 24 week, observational, non-interventional post-marketing surveillance study was to evaluate the safety and tolerability, as well as the efficacy, of the rivastigmine transdermal patch formulation in newly diagnosed patients with Alzheimer's dementia in naturalistic conditions.
Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease. [2019]The antioxidant N-acetylcysteine (NAC) or placebo was administered in a double-blind fashion to patients who met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable AD. Testing for efficacy occurred after 3 and 6 months of treatment. Comparison of interval change favored NAC treatment on nearly every outcome measure, although significant differences were obtained only for a subset of cognitive tasks.
AMPA potentiator treatment of cognitive deficits in Alzheimer disease. [2022]To investigate the efficacy and safety of the positive alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid modulator LY451395 in patients with mild to moderate Alzheimer disease (AD) (Mini-Mental State Examination scores 14 to 26).
The NAAG'ing Concerns of Modeling Human Alzheimer's Disease in Mice. [2021]Studies over the past two decades report significant reductions in brain N-acetylaspartyl glutamate (NAAG) levels in neurodegenerative diseases with associated cognitive impairment, including Alzheimer's disease (AD). Because NAAG is cleaved by glutamate carboxypeptidase II (GCPII), restoration of brain NAAG levels via GCPII inhibition is a potential therapeutic strategy for AD. Herein, studies were conducted to identify an appropriate murine model of AD that recapitulates human brain NAAG changes in order to preclinically evaluate the therapeutic benefit of GCPII inhibition. Our opposing findings of brain NAAG changes in human and mouse AD highlights the limited predictive value of AD mouse models.
Modeling of substrate specificity of the Alzheimer's disease amyloid precursor protein beta-secretase. [2013]The enzyme BACE (beta-site APP-cleaving enzyme) has recently been identified as the beta-secretase that cleaves the amyloid precursor protein (APP) to produce the N terminus of the Abeta peptide found in plaques in the brains of Alzheimer's disease patients. BACE is an aspartic protease similar to pepsin and renin. Comparative modeling of the three-dimensional structure of BACE in complex with its substrate shows that several residues confer specificity of the enzyme for APP. In particular, Arg296 forms a salt-bridge with the P1' Asp of the APP substrate, explaining the unusual preference of BACE among aspartic proteases for a P1' residue that is negatively charged. Several hydrophobic residues in the enzyme form a pocket for the P1 hydrophobic residue (Met in wild-type APP and Leu in APP with the "Swedish mutation" associated with early-onset of Alzheimer's disease). Inhibitors that can bind to the BACE active site may prove useful for drugs to treat and prevent Alzheimer's disease.
Mass spectrometry of purified amyloid beta protein in Alzheimer's disease. [2021]The amyloid beta-protein (A beta) that is progressively deposited in Alzheimer's disease (AD) arises from proteolysis of the integral membrane protein, beta-amyloid precursor protein (beta APP). Although A beta formation appears to play a seminal role in AD, only a few studies have examined the chemical structure of A beta purified from brain, and there are discrepancies among the findings. We describe a new method for the rapid extraction and purification of A beta that minimizes artifactual proteolysis. A beta purified by two-dimensional reverse-phase HPLC was analyzed by combined amino acid sequencing and mass spectrometry after digestion with a lysylendopeptidase. The major A beta peptide in the cerebral cortex of all five AD brains examined was aspartic acid 1 to valine 40. A minor species beginning at glutamic acid 3 but blocked by conversion to pyroglutamate was also found in all cases. A species ending at threonine 43 was detected, varying from approximately 5 to 25% of total A beta COOH-terminal fragments. Peptides ending with valine 39, isoleucine 41, or alanine 42 were not detected, except for one brain with a minor peptide ending at valine 39. Our findings suggest that A beta 1-40 is the major species of beta-protein in AD cerebral cortex. A beta 1-40 and A beta 1-43 peptides could arise independently from beta APP, or A beta 1-43 could be the initial excised fragment, followed by digestion to yield A beta 1-40. These analyses of native A beta in AD brain recommend the use of synthetic A beta 1-40 peptide to model amyloid fibrillogenesis and toxicity in vitro.
Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. [2022]Cerebral deposition of amyloid beta peptide (Abeta) is an early and critical feature of Alzheimer's disease. Abeta generation depends on proteolytic cleavage of the amyloid precursor protein (APP) by two unknown proteases: beta-secretase and gamma-secretase. These proteases are prime therapeutic targets. A transmembrane aspartic protease with all the known characteristics of beta-secretase was cloned and characterized. Overexpression of this protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were cleaved exactly and only at known beta-secretase positions. Antisense inhibition of endogenous BACE messenger RNA decreased the amount of beta-secretase cleavage products, and purified BACE protein cleaved APP-derived substrates with the same sequence specificity as beta-secretase. Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for beta-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease.
Multiwell fluorometric and colorimetric microassays for the evaluation of beta-secretase (BACE-1) inhibitors. [2016]The amyloid beta (Abeta) peptide is responsible for toxic amyloid plaque formation and is central to the aetiology of Alzheimer's disease (AD). It is generated by proteolytic processing of the amyloid precursor protein (APP) by beta-secretase (BACE-1) and gamma-secretase. Consequently, inhibition of BACE-1, a rate-limiting enzyme in the production of Abeta, is an attractive therapeutic approach to the treatment of Alzheimer's disease. This paper reports on improved microtiter plate-based fluorescence and colorimetric assays for the high-throughput screening (HTS) of BACE-1 inhibitors achieved by employing, for the first time, casein fluorescein isothiocyanate (casein-FITC) and N-alpha-benzoyl-D,L-arginine p-nitroanilide (BAPNA) as substrates, since they are known to be readily available and convenient substrates for proteases. The methods are based on the fluorescence enhancement following casein-FITC proteolysis and the visible absorbance of the p-nitroaniline (pNA) produced by BAPNA hydrolysis, with both reactions catalysed by BACE-1. Casein-FITC is a high-affinity substrate (K (m) = 110 nM) for BACE-1, more so than the Swedish (SW) type peptide (a peptide containing the Swedish mutant of APP, a familiar mutation that enhances Abeta production). BACE-1 catalysis of casein-FITC proteolysis exhibited Michaelis-Menten kinetic. Therefore, it was found that BACE-1 was saturable with casein-FITC that was processed in a time- and pH-dependent manner with greater catalytic efficiency than observed for the SW peptide. The enantioselective hydrolysis of L-BAPNA by BACE-1 was observed. L-BAPNA was hydrolysed ten times more efficiently by BACE-1 than the WT (wild-type peptide). The novel methods were validated using a FRET assay as an independent reference method. Therefore, in order to select new leads endowed with multifunctional activities, drugs for Alzheimer's disease (AD) - potent acetylcholinesterase (AChE) inhibitors - were tested for BACE-1 inhibition using the proposed validated assays. Among these, donepezil, besides being an acetylcholinesterase inhibitor, was also found to be a BACE-1 inhibitor that displayed submicromolar potency (170 nM).