Genistein as a Possible Treatment for Alzheimer's Disease.

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Effect of Activation of the Receptor PPARg/RXR as a Possible Treatment for Alzheimer's Disease. Role of Genistein.

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Dietary Supplement: Genistein
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Product: Genistein<br>60 mg of genistein BID for 360 days. Intervention: Product: Genistein | Dietary Supplement: Genistein<br>* Subjects will be randomized 1:1 to receive 360 days of double blind treatment of genistein.<br>* Other names: Fisiogen;|
| Placebo Comparator: Product: Placebo<br>1 placebo capsule BID for 360 days. Intervention: Product: Placebo | Other: Placebo<br>* 360 days of double blind treatment of placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in 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. | Day 0 and day 360 (plus or minus 7 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in MMSE. | Change from baseline to the end of the treatment, and the change between the treatment group and the placebo group. | Day 0, day 180, day 360, (plus or minus 7 days) | 
| Changes in T@M (Memory Alteration Test). | Change from baseline to the end of the treatment, and the change between the treatment group and the placebo group.This 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) | Day 0, day 180, day 360, (plus or minus 7 days) | 
| Changes in TAVEC (Verbal Learning Test Spain-COmplutense). | Change from baseline to the end of the treatment, and the change between the treatment group and the placebo group. | Day 0, day 180, day 360, (plus or minus 7 days) | 
| Changes in the Clock test. | Change from baseline to the end of the treatment, and the change between the treatment group and the placebo group. | Day 0, day 180, day 360, (plus or minus 7 days) | 
| Changes in the Barcelona Test. | Change from baseline to the end of the treatment, and the change between the treatment group and the placebo group. | Day 0, day 180, day 360, (plus or minus 7 days) | 
| Changes in Rey Complex figure Test. | Change from baseline to the end of the treatment, and the change between the treatment group and the placebo group. | Day 0, day 180, day 360, (plus or minus 7 days) | 
| Changes in Genistein Pharmacokinetics. | Change from baseline to the end of the treatment,and the change between the treatment group and the placebo group. | Day 0, day 360, (plus or minus 7 days) | 
| Changes in Equol Pharmacokinetics. | Change from baseline to the end of the treatment,and the change between the treatment group and the placebo group. | Day 0, day 360, (plus or minus 7 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment, Genistein, Alzheimer's disease, Cerebrospinal fluid, Amyloid beta