A Randomized Controlled Study to Evaluate the Effect of Bexarotene - an RXR Agonist - on Beta-Amyloid and Apolipoprotein E Metabolism in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Area under the effect curve for newly generated beta-Amyloid (clearance phase),
研究概览
简要总结
The primary objective of this proof of mechanism pilot clinical trial is to determine if the RXR agonist bexarotene acts in humans to alter the CSF levels of apoE and alter the clearance of Amyloid-Beta
详细描述
This is a double blinded, investigational drug study designed to measure the effect of bexarotene on the clearance of Aβ total and production of apoE in the human brain of young, healthy individuals with the APOE3/3 genotype. From the date of initial subject recruitment to the issuance of a final study report and closeout activities, the expected total study duration is 6 to 10 months.
Each participant will be screened for eligibility and randomized to receive either oral bexarotene or placebo control ("Test Article").The study has the potential to demonstrate the pharmacodynamic properties of a novel treatment approach to Alzheimer's disease. The primary biomarker measurements obtained from this study are believed to be highly dynamic and able to provide a rapid read-out of the biologic activity of the candidate therapeutic under study. In addition, exploratory analysis will involve a proteomics-based screen to identify proteins within both blood and CSF that are induced by the Test Article, thereby potentially identifying new biomarkers that can be used in future clinical trials to demonstrate bexarotene action and target engagement.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Young healthy adults (age 21-50)
- •APOE3/3 genotype
排除标准
- •Contraindications for blood or CSF sampling
- •Bleeding disorder or taking anticoagulants/antiplatelets
- •Chronic active infection
- •Blood donation within the past month
- •Active drug/alcohol dependence or abuse history with in the last 12 months
- •Thyroid dysfunction
- •High triglycerides (>3.5 mmol/L)
- •High cholesterol (>4.0 mmoL/L)
- •Leukopenia, including low neutrophil count (<3 x 10^9/L)
- •Neurological or psychiatric disorders
- •Homeless or prisoner
- •Pregnancy
- •Incapable of self-informed consent
- •Blood borne disease (HIV, Hepatitis)
- •Actively smoking and incapable of using nicotine patches
- •Known drug allergy to pain medication or local anesthetic
- •Subjects that have participated in another study in the last 30 days
- •Abnormalities in lumbar spine previously known within 12 months
- •APOE2 or APOE4 allele
- •Abnormal EKG
研究组 & 干预措施
Bexarotene
The subjects will be administered three (3) capsules of Targretin™ (75 mg/capsule) on a twice daily basis (450 mg/day) for five days
干预措施: Bexarotene (Drug)
Placebo
The subjects will be administered three (3) capsules of Avicel PH on a twice daily basis (450 mg/day) for five days.
干预措施: Placebo (Drug)
结局指标
主要结局
Area under the effect curve for newly generated beta-Amyloid (clearance phase),
时间窗: 21 - 48 hr
Area under the effect curve from 21-48h for newly generated beta-Amyloid (clearance phase), which is computed for each individual as the area under the curve of the clearance portion of the labeled beta-Amyloid curve between 21 hour and 48 hours, normalized by plasma free leucine levels.
次要结局
- Fractional clearance rate of beta-Amyloid peptide in CNS(21 - 36 hrs)