Bumetanide in Patients With Alzheimer's Disease (BumxAD)

Stanford University

Status and phase: Enrolling; Phase 2

Conditions: Alzheimer Disease

Treatments: Drug: Bumetanide; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06052163

IRB-69153

Details and patient eligibility

About

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.

Enrollment: 40 estimated patients

Sex: All

Ages: 50 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 3 patient groups, including a placebo group

Bumetanide low dose

Active Comparator group

Description:

15 participants will take bumetanide low dose orally for 6 months and will be evaluated on cognitive and functional tests. Participants blood samples will be tested for levels of proteins involved in Alzheimer's disease.

Treatment:

Drug: Bumetanide

Bumetanide high dose

Active Comparator group

Description:

15 participants will take bumetanide high dose orally for 6 months and will be evaluated on cognitive and functional tests. Participants blood samples will be tested for levels of proteins involved in Alzheimer's disease.

Treatment:

Drug: Bumetanide

Placebo

Placebo Comparator group

Description:

10 participants will take placebo orally for 6 months and will be evaluated on cognitive and functional tests. Participants blood samples will be tested for levels of proteins involved in Alzheimer's disease.

Treatment:

Drug: Placebo