GENIAL: Genistein as a Possible Treatment for Alzheimer's Disease.

Sponsor

Fundación para la Investigación del Hospital Clínico de Valencia (Other)

Overall Status

Completed

CT.gov ID

NCT01982578

Collaborator

University of Valencia (Other)

Enrollment

Locations

Arms

Actual Duration (Months)

13.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Dietary Supplement: Genistein Other: Placebo	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 1, 2017

Actual Primary Completion Date :

Sep 30, 2020

Actual Study Completion Date :

Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Product: Genistein 60 mg of genistein BID for 360 days. Intervention: Product: Genistein	Dietary Supplement: Genistein Subjects will be randomized 1:1 to receive 360 days of double blind treatment of genistein. Other Names: Fisiogen
Placebo Comparator: Product: Placebo 1 placebo capsule BID for 360 days. Intervention: Product: Placebo	Other: Placebo 360 days of double blind treatment of placebo.

Arm

Intervention/Treatment

Experimental: Product: Genistein

60 mg of genistein BID for 360 days. Intervention: Product: Genistein

Dietary Supplement: Genistein

Subjects will be randomized 1:1 to receive 360 days of double blind treatment of genistein.

Other Names:

Fisiogen

Placebo Comparator: Product: Placebo

1 placebo capsule BID for 360 days. Intervention: Product: Placebo

Other: Placebo

360 days of double blind treatment of placebo.

Outcome Measures

Primary Outcome Measures

Changes in Amyloid beta concentration in cerebrospinal fluid (CSF) [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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.