This is a proof-of-concept phase 2 clinical trial to investigate the safety and effect of the phytoestrogenic supplement PhytoSERM on regional brain metabolism by fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) in peri- and postmenopausal women. The investigators hypothesize that there will be a significant difference between the PhytoSERM group and placebo group in glucose brain metabolism.
This is a double-blinded, randomized, placebo-controlled, parallel designed, proof-of-concept phase 2 clinical trial to determine effect of PhytoSERM in regional brain metabolism, cognition and vasomotor symptoms in menopausal women. PhytoSERM or placebo pills will be administered orally once a week over 24 weeks. Safety and tolerability will also be assessed over the duration of the study. To determine eligibility, all participants will undergo cognitive assessment, physical and neurological examination, imaging scans, electrocardiogram (ECG), clinical/safety laboratory assessment, and interviews. After a 2-4-week screening period, participants will be randomized to study intervention (PhytoSERM 50mg administered orally, once per day) or matching placebo, in a 1:1 allocation. Brain imaging to evaluate the primary endpoint (standardized uptake value ratio (SUVR) by FDG-PET) will be conducted at screening and 24 weeks (6 months). Study participants will be asked to complete a total of 7 study visits. All participants will be enrolled at a single site, at the Alzheimer's Prevention Program (APP) at Weill Cornell Medical Centre (WCMC, New York). This study protocol will include an embedded single-dose, 24-hour pharmacokinetic (PK) study in a subset of 12 participants which will begin after the first dose of the study intervention.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
100
PhytoSERM is a dietary supplement containing equal amounts of genistein (16.7 mg ± 10%), daidzein (16.7 mg ± 10%) and S-equol (16.7 mg ± 10%).
Placebo product with identical shape, size and color will be produced with absence of S-equol, daidzein and genistein. Ingredients include calcium carbonate, comprecel M102, croscarmellose sodium, stearic acid, Zeofree 5162, magnesium stearate, carnauba wax, coating cellulose clear (PEG), coating white (PEG), water.
University of Arizona / Clinical & Translational Sciences Research Center (CATS
Tucson, Arizona, United States
The Alzheimer's Prevention Program / Weill Cornell Medicine
New York, New York, United States
Standardized uptake value ratio (SUVR) by 18F-FDG PET
Regional brain glucose metabolism SUVR
Time frame: Baseline to 24 weeks
Trail Making Test (TMT)
The TMT is scored by how long it takes to complete the test. For TMT-B, an average score is 75 seconds, and a deficient score is greater than 273 seconds. Less is better.
Time frame: Baseline to 24 weeks
List Sorting Working Memory Test
Test scores consisted of combined total items correct on the one- and two-list versions of the task (maximum 28). The raw sum score is then transformed to a standardized t-metric. More is better.
Time frame: Baseline to 24 weeks
Picture Sequence Memory Test
Maximum raw score of 48 for ages 20-60 years. More is better.
Time frame: Baseline to 24 weeks
Auditory Verbal Learning Test
The Rey is scored by taking the sum of the number of words recalled across all trials (possible range is 0-45 words).
Time frame: Baseline to 24 weeks
Oral Symbol Digit Test
The Oral Symbol Digit Test is scored as the number of items answered correctly in 120 seconds (possible range is 0-144).
Time frame: Baseline to 24 weeks
Hot flash Frequency Composite
Hot flash frequency and severity scores. Less is better.
Time frame: Baseline to 24 weeks
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Menopause Rating Scale (MRS) Score
The total score of the MRS ranges between 0 (asymptomatic) and 44 (highest degree of complaints).
Time frame: Baseline to 24 weeks
Pittsburgh Sleep Quality Index
A global sum of "5" or greater indicates a "poor" sleeper.
Time frame: Baseline to 24 weeks
Positive and Negative Affect Scale
Positive and negative affect items are summed separately and range from 0 to 50 with higher scores indicating higher positive affect and higher negative affect respectively.
Time frame: Baseline to 24 weeks
Beck Depression Inventory - II
Maximum score is 63. Higher scores represent greater depressive symptoms.
Time frame: Baseline to 24 weeks
Pharmacokinetics: Peak Plasma Concentration (Cmax)
The highest concentration of each phytoestrogen in the blood after a dose is given.
Time frame: Baseline
Pharmacokinetics: Time of peak concentration (tmax)
Time required to achieve peak plasma levels.
Time frame: Baseline
Pharmacokinetics: Half-life (t1/2)
The time required for plasma concentration of phytoSERMs to decrease by 50%
Time frame: Baseline
Pharmacokinetics: Area under the plasma concentration versus time curve (AUC)
The concentration of phytoSERMs in blood plasma as a function of time. Gives insight into the extent of exposure to phytoSERM and its clearance rate from the body.
Time frame: Baseline