Bumetanide in Patients With Alzheimer's Disease

Alzheimer Disease Clinical Trial

— BumxAD  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06052163
• Other study ID #: IRB-69153
• Status: Recruiting
• Phase: Phase 2
• Start date: April 10, 2023
• Est. completion date: April 15, 2025

Study information

• Verified date: April 2024
• Source: Stanford University
• Contact: Mina L Kim
• Phone: (650) 387-1559
• Email: minakim[@]stanford.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 15, 2025
• Est. primary completion date: April 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

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.
• Placebo
A placebo has no active properties and is taken orally.

Locations

Country	Name	City	State
United States	Stanford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & 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. — View 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. Erratum In: Nat Aging. 2021 Dec;1(12):1202. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from baseline in The Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog13)	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	6 months
Secondary	Changed from baseline in the clinical dementia rating scale sum of boxes (CDR-SoB)	CDR-SoB evaluates function with total possible score of 0 to 18 with higher scores indicating more impairment	6 months

External Links

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