PhytoSERM to Prevent Menopause Associated Decline in Brain Metabolism and Cognition

NCT05664477 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: Phyto-2022-01R01AG075122
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Menopause; Cognitive Change; Brain Disorder, Metabolic

Outcome Measures

Primary Outcomes (1)

• Standardized uptake value ratio (SUVR) by 18F-FDG PET

  Regional brain glucose metabolism SUVR

  Baseline to 24 weeks

Secondary Outcomes (14)

• Trail Making Test (TMT)

  Baseline to 24 weeks

• List Sorting Working Memory Test

  Baseline to 24 weeks

• Picture Sequence Memory Test

  Baseline to 24 weeks

• Auditory Verbal Learning Test

  Baseline to 24 weeks

• Oral Symbol Digit Test

  Baseline to 24 weeks

Other Outcomes (11)

• Regional brain volume

  Baseline to 24 weeks

• Fractional Anisotropy

  Baseline to 24 weeks

• Quantitative anisotropy

  Baseline to 24 weeks

Study Arms (2)

PhytoSERM group

EXPERIMENTAL

PhytoSERM 50mg tablet composed of the phytoestrogens daidzein, genistein and S-equol, administered orally every day for 24 weeks.

Dietary Supplement: PhytoSERM

Placebo group

PLACEBO COMPARATOR

Placebo product with identical shape, size and color with absence of daidzein, genistein, and S-equol. Administered orally every day for 24 weeks.

Drug: Placebo

Interventions

Placebo DRUG

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.

Placebo group

PhytoSERM DIETARY_SUPPLEMENT

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%).

PhytoSERM group

Eligibility Criteria

• Age: 45 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Peri- or postmenopausal women with the latter defined as last menstrual period (LMP) completed ≥ 60 days and ≤ 4 years, per the Stages of Reproductive Aging Workshop (STRAW) criteria.
• Age 45-60 years.
• Presence of hot flashes ≥ 7 per day.
• In good general health as evidenced by medical history.
• Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be not clinically significant by the investigator.
• No medical contraindications to study participation.
• Stable medications for 4 weeks prior to the baseline visits.
• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Ability to take oral medication and be willing to adhere to the PhytoSERM regimen.
• For females of reproductive potential: Negative pregnancy test and use of highly effective contraception by male partner for at least 1 month prior to screening and agreement to use such a method during study participation.
• Fluent in English or Spanish.

You may not qualify if:

• Known allergies to isoflavones or soy-based products.
• Evidence of cognitive impairment on the Mini-Mental State Examination (total score \< 27).
• Pregnancy
• Use of estrogen or progestin compounds within 8 weeks of baseline.
• Use of investigational agent within 12 weeks of baseline.
• Concurrent neurologic, systemic, or psychiatric disease that would influence cognition or ability to provide informed consent and to participate.
• Known or suspected estrogen-dependent neoplasia, active neoplastic disease, history of breast cancer, or at risk of developing breast cancer, endometrial hyperplasia.
• History of epilepsy, focal brain lesion, head injury with loss of consciousness or Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse.
• Thrombophlebitis, thrombosis, thromboembolic disorders, myocardial infarction, ischemic heart disease, cerebrovascular accident, stroke, transient ischemic attack (TIA).
• Current use of tobacco or a history of alcohol abuse.
• Use of drugs, herbs, or dietary supplements to treat menopausal or cognitive symptoms less than 8 weeks prior to baseline.
• Evidence of any significant clinical disorder or laboratory finding.
• Known allergy to soy-derived products/ proteins or branded over the counter products; hypersensitivity to estrogens or progestins.
• Visual and auditory acuity inadequate for neuropsychological testing
• Inability to undergo MRI scans

Sponsors & Collaborators

• Roberta Brinton: lead
• Cornell University: collaborator
• ADM Diagnostics: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (2)

University of Arizona / Clinical & Translational Sciences Research Center (CATS

Tucson, Arizona, 85721, United States

Location

The Alzheimer's Prevention Program / Weill Cornell Medicine

New York, New York, 10021, United States

Location

Related Publications (2)

• Hernandez G, Zhao L, Franke AA, Chen YL, Mack WJ, Brinton RD, Schneider LS. Pharmacokinetics and safety profile of single-dose administration of an estrogen receptor beta-selective phytoestrogenic (phytoSERM) formulation in perimenopausal and postmenopausal women. Menopause. 2018 Feb;25(2):191-196. doi: 10.1097/GME.0000000000000984.

  PMID: 28926513 BACKGROUND

• Schneider LS, Hernandez G, Zhao L, Franke AA, Chen YL, Pawluczyk S, Mack WJ, Brinton RD. Safety and feasibility of estrogen receptor-beta targeted phytoSERM formulation for menopausal symptoms: phase 1b/2a randomized clinical trial. Menopause. 2019 Aug;26(8):874-884. doi: 10.1097/GME.0000000000001325.

  PMID: 30889096 BACKGROUND

MeSH Terms

Conditions

Brain Diseases, Metabolic

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Roberta D Brinton, PhD

  University of Arizona

  PRINCIPAL INVESTIGATOR

• Gerson D Hernandez, MD, MPH

  University of Arizona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Regents Professor and Director of the Center for Innovation in Brain Science

Study Record Dates

• First Submitted: September 8, 2022
• First Posted: December 23, 2022
• Study Start: January 10, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

US (2)