Genistein as a Possible Treatment for Alzheimer's Disease. (GENISTEÍNA_2)

Study Description

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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 180 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

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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.
Study Start Date :	November 2013
Estimated Primary Completion Date :	September 2017
Estimated Study Completion Date :	September 2018

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Product: Genistein; 60 mg of genistein BID for 180 days. Intervention: Product: Genistein	Dietary Supplement: Genistein; Subjects will be randomized 1:1 to receive 180 days of double blind treatment of genistein.; Other Name: Fisiogen
Placebo Comparator: Product: Placebo; 1 placebo capsule BID for 180 days. Intervention: Product: Placebo	Other: Placebo; 180 days of double blind treatment of placebo.

Outcome Measures

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Primary Outcome Measures :

1. 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 :

1. 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) ]
2. 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) ]
3. 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)
4. 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) ]
5. 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) ]
6. 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) ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

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

Locations

Spain
Hospital de La Ribera	Recruiting
Alzira, Valencia, Spain, 46600
Contact: Francisco Tarazona, MD +34 962 458 100 FJTarazona@Hospital-Ribera.com
Hospital Clínico Universitario de Valencia	Recruiting
Valencia, Spain, 46010
Contact: José Miguel Lainez, M.D. 963 86 26 00 jlaineza@medynet.com
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)

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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations 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 History of Changes
Other Study ID Numbers:	INC-GEN-2013-01; U1111-1150-4063 ( Other Identifier: World Health Organization )
First Posted:	November 13, 2013
Last Update Posted:	August 3, 2015
Last Verified:	July 2015

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