Phase IIa, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Tolerability of Bumetanide in Patients With Alzheimer's Disease.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Related Adverse Events
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Bumetanide (Drug)
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.
干预措施: Bumetanide (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Treatment-Related Adverse Events
时间窗: 6 months
Number of participants with adverse events including clinical signs and symptoms, change in vital signs, ECGs, laboratory safety tests, and suicidality assessments.
次要结局
- 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)
研究者
Kyan Younes
Clinical Assistant Professor
Stanford University