Bumetanide in Patients With Alzheimer's Disease

Summary

This study aims to investigate bumetanide in patients with biologically confirmed Alzheimer's disease (AD). Bumetanide is a potent diuretic administered orally and is FDA approved for the treatment of edema and hypertension. Repurposing bumetanide as a medication for AD has been proposed based on data that demonstrated its ability to "flip" the APOE genotype-dependent transcriptomic signatures in AD mouse and cell culture models. Critically, this discovery was subsequently explored in Electronic Health Record cohorts, which revealed that among individuals over the age of 65, bumetanide exposure was significantly associated with a lower prevalence of AD in three independent datasets. Primary Objective: To evaluate the safety and tolerability of bumetanide when administered to participants with biomarker-confirmed Alzheimer's disease. Secondary Objective: To evaluate the clinical and biomarker effects of bumetanide in participants with mild cognitive impairment or mild dementia due to Alzheimer's disease.

Timeline

Start

2023-04-10

Primary completion

2026-12-15

Completion

2026-12-15

Publications

• Background Graber-Naidich A, Lee J, Younes K, Greicius MD, Le Guen Y, He Z. Bumetanide Exposure Association with Alzheimer's Disease Risk. Res Sq [Preprint]. 2023 Feb 28:rs.3.rs-2574215. doi: 10.21203/rs.3.rs-2574215/v1.
• Background Taubes A, Nova P, Zalocusky KA, Kosti I, Bicak M, Zilberter MY, Hao Y, Yoon SY, Oskotsky T, Pineda S, Chen B, Jones EAA, Choudhary K, Grone B, Balestra ME, Chaudhry F, Paranjpe I, De Freitas J, Koutsodendris N, Chen N, Wang C, Chang W, An A, Glicksberg BS, Sirota M, Huang Y. Experimental and real-world evidence supporting the computational repurposing of bumetanide for APOE4-related Alzheimer's disease. Nat Aging. 2021 Oct;1(10):932-947. doi: 10.1038/s43587-021-00122-7. Epub 2021 Oct 11.

Drugs

Indications