BumxAD: Bumetanide in Patients With Alzheimer's Disease

• Sponsor: Stanford University (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06052163
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 3
• Anticipated Duration (Months): 24
• Patients Per Site Per Month: 1.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: Bumetanide; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Bumetanide low dose, 15 participants Bumetanide high dose, 15 participants Placebo, 10 participantsBumetanide low dose, 15 participants Bumetanide high dose, 15 participants Placebo, 10 participants
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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.
• Anticipated Study Start Date: Oct 15, 2023
• Anticipated Primary Completion Date: Oct 15, 2025
• Anticipated Study Completion Date: Oct 15, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: 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.; Other Names: Bumex
Active Comparator: 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.	Drug: 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.; Other Names: Bumex
Placebo Comparator: 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.	Drug: Placebo; A placebo has no active properties and is taken orally.

Outcome Measures

Primary Outcome Measures

1. Incidence of Treatment-Related Adverse Events [6 months]

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

Secondary Outcome Measures

1. Change from baseline in The Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog13) [6 months]

   The ADAS-Cog evaluates cognition and is scored from 0 to 90 points with a score of 0 indicating no impairment, and a score of 90 indicating maximum impairment

2. Changed from baseline in the clinical dementia rating scale sum of boxes (CDR-SoB) [6 months]

   CDR-SoB evaluates function with total possible score of 0 to 18 with higher scores indicating more impairment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Kyan Younes, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Stanford Neurology & Neurological Sciences Clinical Trials
• Stanford Alzheimer's Disease Research Center Clinical Trials and Research Studies

Publications

• Graber-Naidich A, Lee J, Younes K, Greicius MD, Guen YL, He Z. Bumetanide Exposure Association with Alzheimer's Disease Risk. Res Sq. 2023 Feb 28:rs.3.rs-2574215. doi: 10.21203/rs.3.rs-2574215/v1. Preprint.
• 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. Erratum In: Nat Aging. 2021 Dec;1(12):1202.

• Responsible Party: Kyan Younes, Clinical Assistant Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT06052163
• Other Study ID Numbers: IRB-69153
• First Posted: Sep 25, 2023
• Last Update Posted: Sep 25, 2023
• Last Verified: Sep 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Alzheimer Disease; Bumetanide

Study Results

No Results Posted as of Sep 25, 2023