Senolytics To Alleviate Mobility Issues and Neurological Impairment in Aging
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Neurovascular Coupling
研究概览
简要总结
The purpose of this pilot study is to demonstrate the safety and feasibility of administering intermittent doses of Dasatinib and Quercetin (D+Q) in older adults at risk of Alzheimer's disease (AD). The study will evaluate whether giving D+Q may improve cerebral blood flow regulation, mobility, and cognition in older adults, and thus may prevent progression to Alzheimer's disease.
详细描述
The investigators will conduct a 12-week single arm, open label, pre-post pilot study in 12 adults aged 65 or older with slow gait speed (<1.0 m/sec) and Mild Cognitive Impairment (MCI, defined as a Telephone Montreal Cognitive Assessment Score (MoCA) <19). Participants will be asked to take 100mg of Dasatinib and 1,250mg of Quercetin for 2 consecutive days, every two weeks over a period of 12 weeks (12 doses in total, given over 6 cycles).
At baseline, enrolled participants will undergo gait speed and neurocognitive testing, and provide blood and urine to evaluate biomarkers of senescence. At visits 3,4, 6, and 7, participants will have safety labs drawn, and the study team will assess medication adherence and adverse events. At visits 2, 5, and 8, participants will undergo cognitive assessments, gait speed testing, cerebral blood flow and neurovascular coupling testing. At the final study visit, participants will again provide blood and urine to assess biomarkers of senescence.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women >/= 65 years
- •Ambulatory,
- •Community dwelling,
- •Slow gait speed (<1 m/second),
- •Mild Cognitive Impairment (Telephone MoCA score <21, which is indicative of cognitive impairment)
- •Exclusion Criteria, or as per clinical judgment:
- •Telephone MoCA score <10 points
- •Unwilling to take study medications or follow study protocol
- •Inability to independently perform Katz Activities of Daily Living (ADLs),
- •Allergies to Dasatinib or Quercetin,
- •Hospitalization within 6 months,
- •Unstable coronary artery disease (myocardial infarction within 6 months or angina),
- •Stroke or transient ischemic attack in the past 6 months,
- •Chronic heart failure,
- •Current or chronic history of liver disease,
- •Neurodegenerative disease including Parkinson's disease,
- •Chronic renal disease,
- •Drug or alcohol abuse in the last 5 years,
- •QTc prolongation,
- •Thrombocytopenia,
- •Neutropenia,
- •Prolonged prothrombin time or INR,
- •Indications of current fluid retention,
- •History or current diagnosis of pulmonary hypertension,
- •Inability to insonate the middle cerebral artery through a temporal bone window on at least one side using transcranial Doppler ultrasound, or
- •Chronic use of any of the following medications: anti-arrhythmic medications, antipsychotics, anxiolytics, anti-platelet or anti-coagulant medications other than aspirin, quinolone antibiotics, or drugs metabolized by the same liver enzymes as Quercetin or Dasatinib.
排除标准
- 未提供
研究组 & 干预措施
Arm 1
Dasatinib and Quercetin
干预措施: Dasatinib (Drug)
Arm 1
Dasatinib and Quercetin
干预措施: Quercetin (Drug)
结局指标
主要结局
Neurovascular Coupling
时间窗: Screening, 8, and 14 weeks
Change in cerebral blood flow during an N-back cognitive task using transcranial doppler ultrasound.
Executive Function
时间窗: Baseline, 8, and 14 weeks
Assess change in executive cognitive function using TRAILS test, corrected for response time. Higher scores indicate worse executive functioning.
Gait Speed
时间窗: Baseline, 8, and 14 weeks
Assess change in gait speed. Performed without a distracting cognitive task.
Montreal Cognitive Assessment (MoCA) Score
时间窗: Baseline, 8, and 14 weeks
The Montreal Cognitive Assessment evaluates global cognition. Scores range from 0-30 points, with higher scores indicating better cognition
次要结局
- Physical Performance(Baseline, 8, and 14 weeks)
- Mobility(Baseline, 8, and 14 weeks)
- Grip Strength(Baseline, 8, and 14 weeks)
- Gait Speed During Cognitive Task(Baseline, 8, and 14 weeks)
- P16 ink4a Expression in CD3 Positive Cells(Screening and 14 weeks)
- SASP Factors in Blood and Urine(Screening and 14 weeks)
研究者
Lewis Lipsitz
Director, Marcus Institute for Aging Research
Hebrew SeniorLife