Rapamycin - Effects on Alzheimer's and Cognitive Health (REACH)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Change in carbon dioxide or bicarbonate (CO2)
研究概览
简要总结
This study will evaluate the safety, tolerability, and feasibility of 12 month oral rapamycin treatment in older adults with amnestic mild cognitive impairment (aMCI) and early stage Alzheimer's disease (AD).
详细描述
The study will consist of a screening/baseline period of up to 90 days pre-study drug, with a 12-month (+3 day) treatment period with rapamycin, followed by a post-treatment assessment completed within 14 days of the final study drug dose, and a final assessment conducted 6-months (+14 days) after the final study drug dose. The study duration is not expected to exceed 90 weeks for participants.
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)
盲法说明
Quadruple-blind
入排标准
- 年龄范围
- 55 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Both genders and all ethnic groups
- •Ages 55 to 89 years
- •Diagnosis of MCI or AD (Mini Mental Status Examination (MMSE): 18-30; Clinical Dementia Rating Scale (CDR) = 0.5 - 1; California Verbal Learning Test III (CVLT-III) Delayed Recall ≤16% based on age-adjusted norms, clinician approval)
- •Amyloid positivity based on Amyloid PET Imaging
- •Labs: Normal blood cell counts without clinically significant excursions; normal liver and renal function; and glucose control (HbA1c < 6.5%). Fasting lipid panel and prothrombin time/prothrombin time test/international normalized ration (PT/PTT/INR) within normal limits
- •A legally authorized representative (LAR) designated to sign informed consent (if necessary) must attend the Screening visit and accompany the participant to all remaining visits to provide reported outcomes
- •Stable dose of AD medications (Donepezil, rivastigmine, Memantine, galantamine) for at least three months is allowed
排除标准
- •Diabetes (HBA1c≥6.5% or antidiabetic medications)
- •History of skin ulcers or poor wound healing
- •Current tobacco or illicit drug use or alcohol abuse
- •Use of anti-platelet or anti-coagulant medications other than aspirin
- •Current medications that affect cytochrome 450 3A4 (CYP3A4)
- •Immunosuppressant therapy within the last year
- •Chemotherapy or radiation treatment within the last year
- •Current or chronic history of liver or kidney disease or known hepatic or biliary abnormalities
- •Untreated hypertriglyceridemia (fasting triglycerides < 250 mg/dl)
- •Current or chronic history of pulmonary disease or abnormal pulse oximetry (<90%)
- •Chronic heart failure
- •Pregnancy or lactation
- •Recent history (past six months) of myocardial infarction, active coronary artery disease, intestinal disorders, stroke, or transient ischemic attack
- •Significant neurological conditions other than AD or MCI
- •Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg - based on two readings)
- •Active inflammatory, COVID-19, autoimmune, infectious, hepatic, gastrointestinal, malignant, and/or severe mental illness
- •History of, or MRI, or CT positive for, any space occupying lesion, including mass effect or abnormal intracranial pressure, which would indicate contraindications to lumbar puncture
- •Organ transplant recipients
研究组 & 干预措施
RAPA (rapamycin) treatment group
Subjects will receive active drug
干预措施: Rapamycin (Drug)
Placebo group
Subjects will receive placebo
干预措施: Placebo (Other)
结局指标
主要结局
Change in carbon dioxide or bicarbonate (CO2)
时间窗: Baseline to 12 months
A comprehensive metabolic panel is used to measure change in CO2
Number of adverse events
时间窗: Baseline to 12 months
Development or worsening of medical symptoms or problems
Change in albumin
时间窗: Baseline to 12 months
A comprehensive metabolic panel is used to measure change in albumin level
Change in calcium
时间窗: Baseline to 12 months
A comprehensive metabolic panel is used to measure change in calcium levels
Change in glucose level
时间窗: Baseline to 12 months
A comprehensive metabolic panel is used to measure change in glucose level
次要结局
- Change in Gait Speed(Baseline to 12 months)
- Change in Brain Volumetry(Baseline to 12 months)
- Change in Cognition using preclinical Alzheimer's Cognitive Composite 5 (PACC5)(Baseline to 12 months)
- Change in Cognition using Clinical Dementia Rating Scale sum of Boxes (CDR-SOB)(Baseline to 12 months)
- Change in Grip Strength(Baseline to 12 months)
- Change in Functional status(Baseline to 12 months)
- Change in Neuropsychiatric symptoms(Baseline to 12 months)
- Central nervous system penetration of rapamycin(Baseline and 12 months)
- Change in CSF amyloid beta(Baseline to 12 months)
- Change in cerebral glucose metabolism(Baseline to 12 months)