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 180 days, compared to placebo group, in AD patients.
Primary Outcome Measures:
- Amyloid beta concentration in cerebrospinal fluid (CSF). 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. [ Time Frame: Day 0 and day 180 (plus or minus 3 day) ]
Secondary Outcome Measures:
- MMSE. Change from baseline to the end of the treatment, and the change between the treatment group and the placebo group. [ Time Frame: Day 0, day 45, day 180, (plus or minus 3 days) ]
- Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Change from baseline to the end of the treatment, and the change between the treatment group and the placebo group. [ Time Frame: Day 0, day 45, day 180, (plus or minus 3 days) ]
- Memory alteration test (M@t). Change from baseline to the end of the treatment, and the change between the treatment group and the placebo group. [ Time Frame: Day 0, day 45, day 180, (plus or minus 3 days) ]
Is a memory screening test, capable for discriminating between subjects with subjective memory complaints (SMC) (without objective memory impairment) and patients with amnestic mild cognitive impairment (A-MCI) and with mild Alzheimer's disease (AD) (Archives of Gerontology and Geriatrics. 2010 Mar-Apr;50(2):171-4. doi: 10.1016/j.archger.2009.03.005. Epub 2009 Apr 16)
- Neuropsychiatric Inventory (NPI). Change from baseline to the end of the treatment, and the change between the treatment group and the placebo group. [ Time Frame: Day 0, day 45, day 180, (plus or minus 3 days) ]
- Barthel index. Change from baseline to the end of the treatment, and the change between the treatment group and the placebo group. [ Time Frame: Day 0, day 45, day 180, (plus or minus 3 days) ]
- P-TAU concentration in CSF. Change from baseline to the end of the treatment, and the change between the treatment group and the placebo group. [ Time Frame: Day 0 and day 180 (plus or minus 3 day) ]
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| Estimated Enrollment: |
50 |
| Study Start Date: |
November 2013 |
| Estimated Study Completion Date: |
September 2018 |
| Estimated Primary Completion Date: |
September 2017 (Final data collection date for primary outcome measure) |
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Experimental: Product: Genistein
60 mg of genistein BID for 180 days. Intervention: Product: Genistein
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Dietary Supplement: Genistein
Subjects will be randomized 1:1 to receive 180 days of double blind treatment of genistein.
Other Name: Fisiogen
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Placebo Comparator: Product: Placebo
1 placebo capsule BID for 180 days. Intervention: Product: Placebo
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Other: Placebo
180 days of double blind treatment of placebo.
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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.
