Clinical trial NCT06052163: Bumetanide in Patients With Alzheimer's Disease
Official title: Phase IIa, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Tolerability of Bumetanide in Patients With Alzheimer's Disease.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Alzheimer Disease
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2023-09-25
Enrollment: 40
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1. Bumetanide low dose, 15 participants
2. Bumetanide high dose, 15 participants
3. Placebo, 10 participants
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

* Mild cognitive impairment or mild dementia due to Alzheimer's disease.
* Alzheimer's disease medications are planned to remain stable throughout.
* Willingness and ability to complete all aspects of the study including assessments, neuropsychological testing, and MRI.

Exclusion Criteria:

* Clinically significant abnormalities in screening laboratory tests
* Chronic liver disease
* Renal insufficiency
* Poorly managed hypertension
* Participants taking the following concomitant medications, based on the current Prescribing Information for bumetanide: lithium, drugs with ototoxic potential, drugs with nephrotoxic potential, probenecid, and indomethacin.

Primary outcomes:
measure: Incidence of Treatment-Related Adverse Events
timeFrame: 6 months
Secondary outcomes:
measure: Change from baseline in The Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog13)
timeFrame: 6 months
measure: Changed from baseline in the clinical dementia rating scale sum of boxes (CDR-SoB)
timeFrame: 6 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Kyan Younes, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.