Genistein as a Possible Treatment for Alzheimer's Disease.

Alzheimer's Disease Clinical Trial

— GENIAL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01982578
• Other study ID #: INC-GEN-2013-01
• Secondary ID: U1111-1150-4063
• Status: Completed
• Phase: N/A
• Start date: September 1, 2017
• Est. completion date: December 31, 2020

Study information

• Verified date: September 2021
• Source: Fundación para la Investigación del Hospital Clínico de Valencia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: December 31, 2020
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

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

Other:
• Placebo
360 days of double blind treatment of placebo.

Locations

Country	Name	City	State
Spain	Hospital General Universitario	Valencia
Spain	Universitat de València	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
Fundación para la Investigación del Hospital Clínico de Valencia	University of Valencia

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)