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Evaluating Thrombin Inhibition in Alzheimer’s Disease (The BEACON Trial): Protocol for a Pilot Study (Preprint)


 BACKGROUND
 The precise mechanisms whereby cardiovascular risk factors increase the risk of Alzheimer’s disease (AD) have not been delineated. We reported that microvessels isolated from AD brains overexpress a diverse array of neurotoxic and inflammatory proteins, which is consistent with the process of vascular activation. In pre-clinical studies using AD animal models we showed that a vascular activation inhibitor reduced vascular-derived neuroinflammation and improved cognitive performance. Thrombin is a key mediator of cerebrovascular activation in AD.
 
 
 OBJECTIVE
 This study aims to investigate the safety and potential efficacy of the direct thrombin inhibitor dabigatran, in patients with mild cognitive impairment (MCI) or mild AD to decrease vascular-derived neuroinflammation and improve cognitive performance.
 
 
 METHODS
 Participants will be enrolled then evaluated quarterly throughout the 24-month study. This is a 24-month randomized-control, double-blind, placebo-controlled, multicenter, delayed-start, pilot study evaluating thrombin inhibition in people with biomarker-confirmed MCI probably due to AD or mild AD. 40 - 60 participants will be recruited between 50 - 85 years old. In the initial 9-months of study, either dabigatran or placebo will be orally administered to patients at a dose of 150 mg per day. After 9 months of the placebo-control (Phase I), the placebo arm will cross-over to an active, open-label (Phase II) where all patients will be treated with a 150 mg daily dose of dabigatran orally for an additional 12 months. A 3-month non-treatment follow-up period will assess duration of effects.
 
 
 RESULTS
 Beginning in July 2019, and concluding in August 2022, this study is expected to publish final results in January 2023.
 
 
 CONCLUSIONS
 BEACON is a first-in-kind randomized clinical trial targeting thrombin activation in AD therapeutics. This trial will stimulate translational investigations of an FDA-approved drugs in a newly defined therapeutic areas.
 
 
 CLINICALTRIAL
 Clinicaltrials.gov NCT03752294
