Effect of Activation of the Receptor PPARg/RXR as a Possible Treatment for Alzheimer's Disease. Role of Genistein.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Changes in Amyloid beta concentration in cerebrospinal fluid (CSF)
研究概览
简要总结
Genistein is an isoflavone that has antioxidant and neuroprotective effects on Alzheimer's disease (AD).
A few years ago our group reported that genistein increased PPARg (peroxisome proliferator activated receptor gamma) levels. By the way, activation of retinoid X receptor (RXR)-PPARg dimer, will make overexpressing apolipoprotein E (apoE), which mediates the degradation of amyloid beta (AB). Therefore, we believe that if this phytoestrogen administration increases the availability of the transcription factor, it can increase apoE, and also AB degradation.
The main aim of this study is to determinate the effect of 60 mg BID of genistein administration, during 360 days, compared to placebo group, in AD patients.
详细描述
Alzheimer's disease is devastating in terms of personal wellbeing as well as for society. Any effort to prevent and/or treat this disease is always sought after. Recently, an exciting new possibility was opened by modulating a cellular component called RXR-PPARG. A successful experimental treatment for Alzheimer's was found by activating RXR. But we previously showed that a component of soya, i.e., genistein, is able to activate the other part of the RXR-PPARG molecule, i.e., the PPARG moiety. Genistein, moreover, does not have the undesirable effect of bexarotene and is a food component. Our preliminary results in animals indicate that genistein is effective in the treatment of experimental Alzheimer's in mice. Epidemiological evidence shows that individuals who live in Eastern societies who have a high genistein intake (because they eat a lot of soya) have lower rates of Alzheimer's disease.
Thus we propose a controlled clinical trial to test if administration of the food component genistein is able to prevent or cure, at least partially, Alzheimer's disease.
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with mild cognitive impairment (MCI) compatible with prodromal AD.
- •Mini-Mental State Examinations (MMSE) score between over 24 inclusive.
- •CSF levels of AB, p-TAU compatible with AD.
- •18 years or older.
- •Must have a study partner who is able and willing to comply with all required study procedures.
- •Willing and able to provide informed consent by either the subject or subject's legal representative.
排除标准
- •Patient who does not meet the inclusion criteria.
- •Thyroid abnormalities with or without treatment.
- •Immune abnormalities in blood analyses.
- •Patient suffers hormone dependent neoplasia.
- •Take a diet rich on isoflavones.
研究组 & 干预措施
Product: Placebo
1 placebo capsule BID for 360 days. Intervention: Product: Placebo
干预措施: Placebo (Other)
Product: Genistein
60 mg of genistein BID for 360 days. Intervention: Product: Genistein
干预措施: Genistein (Dietary Supplement)
结局指标
主要结局
Changes in Amyloid beta concentration in cerebrospinal fluid (CSF)
时间窗: Day 0 and day 360 (plus or minus 7 day)
The primary study endpoint is the change from baseline to the end of the treatment, and the change between the treatment group and the placebo group.
次要结局
- Changes in the Clock test.(Day 0, day 180, day 360, (plus or minus 7 days))
- Changes in T@M (Memory Alteration Test).(Day 0, day 180, day 360, (plus or minus 7 days))
- Changes in Rey Complex figure Test.(Day 0, day 180, day 360, (plus or minus 7 days))
- Changes in Genistein Pharmacokinetics.(Day 0, day 360, (plus or minus 7 days))
- Changes in the Barcelona Test.(Day 0, day 180, day 360, (plus or minus 7 days))
- Changes in Equol Pharmacokinetics.(Day 0, day 360, (plus or minus 7 days))
- Changes in MMSE.(Day 0, day 180, day 360, (plus or minus 7 days))
- Changes in TAVEC (Verbal Learning Test Spain-COmplutense).(Day 0, day 180, day 360, (plus or minus 7 days))
研究者
Jose Vina
Professor M.D. Ph. D. (hon)
Fundación para la Investigación del Hospital Clínico de Valencia