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

• ClinicalTrials.gov Identifier: NCT01982578
• Recruitment Status: Recruiting
• First Posted: November 13, 2013
• Last Update Posted: July 31, 2019
• Sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
• Collaborator: University of Valencia
• Information provided by (Responsible Party): Jose Vina, Fundación para la Investigación del Hospital Clínico de Valencia

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	Not Applicable

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 (Clinical Trial)
• Estimated Enrollment: 50 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: September 1, 2017
• Estimated Primary Completion Date: September 30, 2020
• Estimated Study Completion Date: December 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 Name: 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 :

1. Changes in Amyloid beta concentration in cerebrospinal fluid (CSF) [ Time Frame: 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 :

1. Changes in MMSE. [ Time Frame: 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.
2. Changes in T@M (Memory Alteration Test). [ Time Frame: 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)
3. Changes in TAVEC (Verbal Learning Test Spain-COmplutense). [ Time Frame: 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.
4. Changes in the Clock test. [ Time Frame: 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.
5. Changes in the Barcelona Test. [ Time Frame: 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.
6. Changes in Rey Complex figure Test. [ Time Frame: 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.
7. Changes in Genistein Pharmacokinetics. [ Time Frame: 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.
8. Changes in Equol Pharmacokinetics. [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Jose Viña, MD PhD (hon); 0034 963864646 ext 64650; jose.vina@uv.es

Locations

Spain

Universitat de València; Recruiting

Valencia, Spain, 46010

Contact: Jose Viña, MD PhD (hon) 0034 963864646 ext 64650 jose.vina@uv.es

Principal Investigator: Jose Viña, MD PhD (hon)

Hospital General Universitario; Recruiting

Valencia, Spain

Contact: Joaquín Escudero, MD, PhD

Sponsors and Collaborators

Fundación para la Investigación del Hospital Clínico de Valencia

University of Valencia

Investigators

• Principal Investigator: Jose Viña, MD PhD (hon); University of Valencia

More Information

• Responsible Party: Jose Vina, Professor M.D. Ph. D. (hon), Fundación para la Investigación del Hospital Clínico de Valencia
• ClinicalTrials.gov Identifier: NCT01982578
• Other Study ID Numbers: INC-GEN-2013-01; U1111-1150-4063 ( Other Identifier: World Health Organization )
• First Posted: November 13, 2013
• Last Update Posted: July 31, 2019
• Last Verified: July 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jose Vina, Fundación para la Investigación del Hospital Clínico de Valencia:

Treatment; Genistein; Alzheimer's disease; Cerebrospinal fluid; Amyloid beta

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Genistein; Anticarcinogenic Agents; Protective Agents; Physiological Effects of Drugs; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Phytoestrogens; Estrogens, Non-Steroidal; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists