NCT06052163

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_2 alzheimer-disease

Timeline
8mo left

Started Apr 2023

Typical duration for phase_2 alzheimer-disease

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress84%
Apr 2023Dec 2026

Study Start

First participant enrolled

April 10, 2023

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

September 18, 2023

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 25, 2023

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 15, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 15, 2026

Last Updated

January 14, 2026

Status Verified

January 1, 2026

Enrollment Period

3.7 years

First QC Date

September 18, 2023

Last Update Submit

January 12, 2026

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

  • Incidence of Treatment-Related Adverse Events

    Number of participants with adverse events including clinical signs and symptoms, change in vital signs, ECGs, laboratory safety tests, and suicidality assessments.

    6 months

Secondary Outcomes (2)

  • Change from baseline in The Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog13)

    6 months

  • Changed from baseline in the clinical dementia rating scale sum of boxes (CDR-SoB)

    6 months

Study Arms (3)

Bumetanide low dose

ACTIVE COMPARATOR

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.

Drug: Bumetanide

Bumetanide high dose

ACTIVE COMPARATOR

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.

Drug: Bumetanide

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

BumetanideDRUG

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.

Also known as: Bumex
Bumetanide high doseBumetanide low dose
PlaceboDRUG

A placebo has no active properties and is taken orally.

Placebo

Eligibility Criteria

Age50 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

RECRUITING

Related Publications (2)

  • 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.

    PMID: 36909637BACKGROUND

  • 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.

    PMID: 36172600BACKGROUND

Related Links

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Bumetanide

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

SulfonamidesAmidesOrganic Chemicalsmeta-AminobenzoatesAminobenzoatesBenzoatesAcids, CarbocyclicCarboxylic AcidsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur Compounds

Study Officials

  • Kyan Younes, MD

    Stanford University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Mina L Kim

CONTACT

(650) 387-1559minakim@stanford.edu

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 1. Bumetanide low dose, 15 participants 2. Bumetanide high dose, 15 participants 3. Placebo, 10 participants
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Clinical Assistant Professor

Study Record Dates

First Submitted

September 18, 2023

First Posted

September 25, 2023

Study Start

April 10, 2023

Primary Completion (Estimated)

December 15, 2026

Study Completion (Estimated)

December 15, 2026

Last Updated

January 14, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)