Effects of Sirolimus on Middle Aged Asymptomatic ApoE4 Carriers
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 225
- 试验地点
- 1
- 主要终点
- Change in Cerebral Blood Flow as measured by MRI
研究概览
简要总结
Alzheimer's disease is a devastating neurodegenerative disease characterized by accumulation of clumps (also called plaques) and bundles of fibers (also called tangles) in the brain, for which there is currently no cure.
Sirolimus (Rapamycin) is an FDA-approved medication which may improve the blood flow to the brain. The purpose of the clinical trial is to find out whether sirolimus can help improve blood flow and energy use in the brain in women ages 45 to 65 who have the ApoE4 gene, a gene which increases the risk of developing Alzheimer's disease later in life.
There will be two arms in this trail, a sirolimus arm and a placebo arm. A placebo is a pill that looks like the study drug, but it does not have any real medicine in it. Participants will be randomized to one arm or the other, but not to both arms. Three study visits over a 12-week period are required.
Participants will: (i) Complete some questionnaires about how well you think; (ii) Complete genetic testing for the ApoE4 gene; (iii) Have blood work, blood pressure and height and weight collected; (iv) Take either Sirolimus or a placebo daily, by mouth, for approximately 4 weeks; (v) Keep a diary of when the sirolimus or placebo is taken; (vi) Complete 2 Magnetic Resonance Imaging (MRI) exams
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Willing and able to provide informed consent
- •Sex assigned at birth: female
- •45-65 years old
- •Able to perform self-care and activities of daily living with no or minimal assistance
- •Post-menopausal status or use of highly effective contraception. Post-menopausal is defined as either
- •12 months of spontaneous amenorrhea with an appropriate clinical profile (e.g., age-appropriate, history of vasomotor symptoms)
- •surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks prior to screening. For oophorectomy alone, post-menopausal status must be confirmed by follow-up hormone level assessment
- •Highly effective contraception includes intrauterine devices (IUD), oral contraceptives, or other hormonal contraceptives including injectables, transdermal patches, implants or vaginal rings, or refraining from heterosexual intercourse during the 4 weeks of taking the study drug and for 2 weeks after no longer taking the study drug
- •Body weight of ≥ 40 kg
- •Ability to effectively communicate with the investigator and comply with study requirements
排除标准
- •Diagnosis of mild cognitive impairment (MCI), dementia, or Alzheimer's disease
- •BMI ≥ 35 (based on MRI feasibility)
- •Type 1 diabetes or poorly controlled type 2 diabetes (HbA1c ≥ 6.5%)
- •History of skin ulcers or poor wound healing
- •Current tobacco or illicit drug use or alcohol abuse (defined as ≥ 3 per day or ≥ 7 per week for women) (Per NIAAA guidelines)
- •Use of anti-platelet or anti-coagulant medications other than aspirin
- •Required use of medications that affect cytochrome P450 3A4 (CYP3A4) or alter cerebral blood flow (see Appendix 1 for tables of excluded medications)
- •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 < 300 mg/dl)
- •Current or chronic significant history of pulmonary disease
- •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
- •Poorly controlled blood pressure (systolic BP > 160 or diastolic BP > 100 mmHg)
- •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 brain lesion, including mass effect or abnormal intracranial pressure
- •Organ transplant recipients
- •History of Stroke
- •History of ruptured intracranial aneurysm
- •History of malignancy within the past 2 years, with the following exceptions:
- •Localized basal cell or squamous cell carcinoma of the skin
- •Prostate cancer confined to the gland (AJCC stage T2N0M0 or better)
- •Cervical carcinoma in situ
- •Breast cancer localized to the breast
- •History of epilepsy
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
Sirolimus
干预措施: Sirolimus (rapamycin) (Drug)
结局指标
主要结局
Change in Cerebral Blood Flow as measured by MRI
时间窗: Baseline to 4 weeks
Rate of blood perfusion expressed as mL/100g/min globally and regionally
次要结局
- Measurement of blood brain barrier by MRI(Baseline to 4 weeks)
- Measurement of brain oxygenation by MRI(Baseline to 4 weeks)
- Measure the change in plasma Marker-cytokine from baseline to post-treatment(Baseline to 4 weeks)
- Measure baseline to post-treatment changes in Plasma Markers-AD pathology(Baseline to 4 weeks)
- Measure brain function connectivity by fMRI(Baseline to 4 weeks)
- Measurement of glucose uptake in the brain by PET imaging(Baseline to 4 weeks)
- Measure the change in plasma Marker-cytokine using a Meso Scale Discovery (MSD) analyzer.(Baseline to 4 weeks)
- Measure baseline to post-treatment changes in Plasma Markers-AD pathology using a Meso Scale Discovery (MSD) analyzer(Baseline to 4 weeks)
研究者
Ai-Ling Lin, PhD
Professor of Radiology
University of Missouri-Columbia