Effect of mTOR Inhibition and Other Metabolism Modulating Interventions on the Elderly: Immune, Cognitive, and Functional Consequences ((Substudy E - RAPA cMRI With LGE)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Systolic Function
研究概览
简要总结
The ability to mount an effective immune response declines with age, leaving the elderly increasingly susceptible to infectious diseases and cancer. Rapamycin, an FDA approved drug to prevent transplant rejection, increases the lifespan and healthspan of mice and ameliorates age-related declines in immune responsiveness, cancer survival, and cognition in laboratory animals. Investigators are conducting a translational trial to test whether rapamycin also improves life functions in humans focusing on elderly persons (aged 70-95).
Substudy E will evaluate the Rapamycin and Cardiac Function.
详细描述
The main study has completed and results are reported (NCT02874924)
Purpose of Sub-study E - Rapamycin and cMRI to evaluate cardiac function:
The over-arching hypothesis is that RAPA treatment will effect simultaneous improvement in parameters known to be negatively impacted by aging. For example, systemic inflammation is higher in older individuals and contributes to the development of age-related pathologies affecting both the heart and the vasculature. In particular, evidence indicates that aging-associated alterations in inflammatory and pro-fibrotic pathways are critically involved in the etiology of age-related declines. The study team hypothesize that mTOR antagonism with RAPA will improve detrimental age-related pathologies affecting the heart in elderly humans.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 70 Years 至 95 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •men and women 70-95 years of age.
- •Subjects will be in good general health with all chronic diseases (hypertension, coronary artery disease, etc.) clinically stable. Selected subjects will be in good health (Per the World Health Organization good health will be defined as complete physical, mental, and social well-being and not merely the absence of disease or infirmity.
- •For our purposes all diseases or infirmities will be clinically stable whether managed by medications or not.
- •All ethnicities will be included.
- •For cardiac and brain imaging by MRI, a pre-MRI screening questionnaire will be used to assess MRI safety and neurological health.
排除标准
- •Diabetes, (with A1c ≥6.5 or if treated with medication affecting glucose homeostasis History of skin ulcers or poor wound healing,
- •Liver disease,
- •Anti-coagulation,
- •Treatment with drugs known to affect cytochrome P450 3A (diltiazem, erythromycin, etc) due to its role in RAPA metabolism,
- •Treatment (>30days of therapy or long term) with a systemic immunosuppressant (prednisone, etc.) within the last year,
- •History of recent (within 6 months) Myocardial Infarction or active Coronary Disease,
- •Patients with history of recent (within 6 months) intestinal disorders,
- •Exclusion criteria for MRI scan: known claustrophobia, metal implants in soft tissue of the body including pacemakers, aneurysm clips, ferrous metal fragments not anchored to bone (bullets, BBs, shrapnel, metal shavings), implanted medication pumps, and oral-facial metal appliances that are permanently secured but may result in low image quality. Participants may also be excluded for history of severe head trauma, brain injury, brain surgery, inflammation of the brain, or history of seizures.
- •Positive COVID19 test.
研究组 & 干预措施
Rapamycin
Rapamycin 1mg for 8 weeks
干预措施: rapamycin (Drug)
结局指标
主要结局
Systolic Function
时间窗: Baseline to 8 weeks
Test whether RAPA improves systolic function in elderly subjects. Cardiac MRI will be measured before and after 8 weeks of RAPA administration using 3T MRI. From collected MRI data, the study team will quantify change in systolic volumes.
Diastolic Function
时间窗: Baseline to 8 weeks
Test whether RAPA improves diastolic function in elderly subjects.Cardiac MRI will be measured before and after 8 weeks of RAPA administration using 3T MRI. From collected MRI data, the study team will quantify change in diastolic volumes.
Aortic Cross-Sectional Area
时间窗: Baseline to 8 weeks
Test whether RAPA increases aortic compliance in elderly subjects. Aortic MRI will be measured before and after 8 weeks of RAPA using 3T MRI. The study team will quantify distal descending aortic cross-sectional area to assess aortic function/compliance effects.
Aortic Distensibility
时间窗: Baseline to 8 weeks
Test whether RAPA increases aortic compliance in elderly subjects. Aortic MRI will be measured before and after 8 weeks of RAPA using 3T MRI. The study team will quantify change in distal descending aortic distensibility to assess aortic function/compliance effects.
次要结局
未报告次要终点