Protocol of a Phase II Randomized, Multi-Center, Double-Blind, Placebo-Controlled Trial of S-Adenosyl Methionine in Participants with Mild Cognitive Impairment or Dementia Due to Alzheimer&#39;s Disease

Holper, S; Watson, R; Churilov, L; Yates, P; Lim, YY; Barnham, KJ; Yassi, N

Protocol of a Phase II Randomized, Multi-Center, Double-Blind, Placebo-Controlled Trial of S-Adenosyl Methionine in Participants with Mild Cognitive Impairment or Dementia Due to Alzheimer's Disease

Author(s): Holper, S; Watson, R; Churilov, L; Yates, P; Lim, YY; Barnham, KJ; Yassi, N;
Details: Publication Year 2023-05-15,Volume 10,Issue #4,Page 800-809
Journal Title: Journal of Prevention of Alzheimer's Disease
Abstract: BACKGROUND: S-adenosyl methionine (SAMe) is a pivotal metabolite in multiple pathways required for neuronal homeostasis, several of which are compromised in Alzheimer's disease (AD). Correction of the SAMe deficiency that is characteristic of the AD brain may attenuate or prevent pathological processes driving AD-associated neurodegeneration including aberrant tau hyperphosphorylation and DNA hypomethylation. OBJECTIVES: The primary aim is to test the hypothesis that daily treatment with 400 mg oral SAMe for 180 days will lead to a greater reduction from baseline in plasma levels of p-tau181 compared to placebo in patients with mild cognitive impairment or dementia due to AD. DESIGN, SETTING, PARTICIPANTS: This is a phase II, randomized, multi-center, double-blind, placebo-controlled trial among 60 participants with mild cognitive impairment or dementia due to AD. Participants will be randomized in a 1:1 ratio to receive either SAMe or matching placebo, to be taken as an adjunct to their AD standard of care. MEASUREMENTS AND RESULTS: The primary outcome is change in plasma p-tau181 concentration between baseline and following 180 days of treatment, which will be compared between the active and placebo group. Secondary outcomes are the safety of SAMe administration (incidence of serious adverse events), change from baseline in cognitive performance (as measured by the Repeatable Battery for the Assessment of Neuropsychological Status), and epigenetic changes in DNA methylation. CONCLUSION: Demonstration of effective and safe lowering of plasma p-tau181 with SAMe in this phase II trial would pave the way for an exciting field of translational research and a larger phase III trial.
Publisher: Springer Link
Keywords: Humans; *Alzheimer Disease/drug therapy/psychology; *Cognitive Dysfunction/drug therapy; Brain; Double-Blind Method; Methionine/therapeutic use; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Clinical Trials, Phase II as Topic; Alzheimer's disease; DNA methylation; S-adenosyl methionine; dementia; tau hyperphosphorylation
Research Division(s): Population Health And Immunity
PubMed ID: 37874102
Link To PubMed Central Version: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10186290/
Publisher's Version: https://doi.org/10.14283/jpad.2023.55
Open Access at Publisher's Site: https://doi.org/ 10.14283/jpad.2023.55
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-06-30 02:16:08

Last Modified: 2023-11-20 03:24:06