Bumetanide in Patients With Alzheimer's Disease

NCT ID: NCT06052163

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-10
• Study Completion Date: 2026-12-15

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.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Bumetanide low dose

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.

Group Type: ACTIVE_COMPARATOR

Bumetanide

Intervention Type: DRUG

Bumetanide is an FDA approved loop diuretic that has been used for more than three decades to treat edema, congestive heart failure, and hypertension across the life span. It has a well-known side effect profile. Most importantly it can cause dehydration and electrolyte imbalance especially at higher doses. This medication is given to individuals at the similar age group as Alzheimer's disease patients and Alzheimer's disease or cognitive impairment do not preclude its use in patients who need it for its FDA indications. At low doses and when titrated carefully, the medication is well tolerated. However, it has not been studied specifically in Alzheimer's disease patients.

Bumetanide high dose

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.

Group Type: ACTIVE_COMPARATOR

Bumetanide

Intervention Type: DRUG

Bumetanide is an FDA approved loop diuretic that has been used for more than three decades to treat edema, congestive heart failure, and hypertension across the life span. It has a well-known side effect profile. Most importantly it can cause dehydration and electrolyte imbalance especially at higher doses. This medication is given to individuals at the similar age group as Alzheimer's disease patients and Alzheimer's disease or cognitive impairment do not preclude its use in patients who need it for its FDA indications. At low doses and when titrated carefully, the medication is well tolerated. However, it has not been studied specifically in Alzheimer's disease patients.

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

A placebo has no active properties and is taken orally.

Interventions

Bumetanide

Bumetanide is an FDA approved loop diuretic that has been used for more than three decades to treat edema, congestive heart failure, and hypertension across the life span. It has a well-known side effect profile. Most importantly it can cause dehydration and electrolyte imbalance especially at higher doses. This medication is given to individuals at the similar age group as Alzheimer's disease patients and Alzheimer's disease or cognitive impairment do not preclude its use in patients who need it for its FDA indications. At low doses and when titrated carefully, the medication is well tolerated. However, it has not been studied specifically in Alzheimer's disease patients.

Intervention Type: DRUG

Placebo

A placebo has no active properties and is taken orally.

Intervention Type: DRUG

Other Intervention Names

Bumex

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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Kyan Younes

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kyan Younes, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University

Stanford, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mina L Kim

Role: CONTACT

minakim@stanford.edu

(650) 387-1559

Facility Contacts

Mina L Kim

Role: primary

mina.kmiecik@stanford.edu

(650)387-1559

Stanford Memory Disorders research

Role: backup

memoryresearch@stanford.edu

References

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.

Reference Type: BACKGROUND

PMID: 36909637 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36172600 (View on PubMed)

Related Links

https://med.stanford.edu/neurology/research/clinicaltrials.html

Stanford Neurology \& Neurological Sciences Clinical Trials

https://med.stanford.edu/adrc/clinicaltrials.html

Stanford Alzheimer's Disease Research Center Clinical Trials and Research Studies

Other Identifiers

IRB-69153

Identifier Type: -

Identifier Source: org_study_id