Clinical trial NCT01982578: Genistein as a Possible Treatment for Alzheimer's Disease.
Official title: Effect of Activation of the Receptor PPARg/RXR as a Possible Treatment for Alzheimer's Disease. Role of Genistein.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer's Disease
Keywords: Treatment
Genistein
Alzheimer's disease
Cerebrospinal fluid
Amyloid beta
Lead sponsor: Fundación para la Investigación del Hospital Clínico de Valencia
Sponsor class: OTHER
Collaborators: name: University of Valencia
First posted: 2013-11-13
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Changes in Amyloid beta concentration in cerebrospinal fluid (CSF)
timeFrame: Day 0 and day 360 (plus or minus 7 day)
Secondary outcomes:
measure: Changes in MMSE.
timeFrame: Day 0, day 180, day 360, (plus or minus 7 days)
measure: Changes in T@M (Memory Alteration Test).
timeFrame: Day 0, day 180, day 360, (plus or minus 7 days)
measure: Changes in TAVEC (Verbal Learning Test Spain-COmplutense).
timeFrame: Day 0, day 180, day 360, (plus or minus 7 days)
measure: Changes in the Clock test.
timeFrame: Day 0, day 180, day 360, (plus or minus 7 days)
measure: Changes in the Barcelona Test.
timeFrame: Day 0, day 180, day 360, (plus or minus 7 days)
measure: Changes in Rey Complex figure Test.
timeFrame: Day 0, day 180, day 360, (plus or minus 7 days)
measure: Changes in Genistein Pharmacokinetics.
timeFrame: Day 0, day 360, (plus or minus 7 days)
measure: Changes in Equol Pharmacokinetics.
timeFrame: Day 0, day 360, (plus or minus 7 days)
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Universitat de València
city: Valencia
country: Spain
facility: Hospital General Universitario
Study officials:
affiliation: University of Valencia
name: Jose Viña, MD PhD (hon)
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vina J, Escudero J, Baquero M, Cebrian M, Carbonell-Asins JA, Munoz JE, Satorres E, Melendez JC, Ferrer-Rebolleda J, Cozar-Santiago MDP, Santabarbara-Gomez JM, Jove M, Pamplona R, Tarazona-Santabalbina FJ, Borras C. Genistein effect on cognition in prodromal Alzheimer's disease patients. The GENIAL clinical trial. Alzheimers Res Ther. 2022 Nov 4;14(1):164. doi: 10.1186/s13195-022-01097-2.