PhytoSERM to Prevent Menopause Associated Decline in Brain Metabolism and Cognition

NCT ID: NCT05664477

Last Updated: 2025-01-31

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-10
• Study Completion Date: 2027-01-31

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.

Detailed Description

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.

Conditions

Menopause; Cognitive Change; Brain Disorder, Metabolic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

PhytoSERM group

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

Group Type: EXPERIMENTAL

PhytoSERM

Intervention Type: 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%).

Placebo group

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

PhytoSERM

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%).

Intervention Type: DIETARY_SUPPLEMENT

Placebo

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Age 45-60 years.

3. Presence of hot flashes ≥ 7 per day.

4. In good general health as evidenced by medical history.

5. Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be not clinically significant by the investigator.

6. No medical contraindications to study participation.

7. Stable medications for 4 weeks prior to the baseline visits.

8. Provision of signed and dated informed consent form.

9. Stated willingness to comply with all study procedures and availability for the duration of the study.

10. Ability to take oral medication and be willing to adhere to the PhytoSERM regimen.

11. 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.

12. Fluent in English or Spanish.

Exclusion Criteria

1. Known allergies to isoflavones or soy-based products.

2. Evidence of cognitive impairment on the Mini-Mental State Examination (total score < 27).

3. Pregnancy

4. Use of estrogen or progestin compounds within 8 weeks of baseline.

5. Use of investigational agent within 12 weeks of baseline.

6. Concurrent neurologic, systemic, or psychiatric disease that would influence cognition or ability to provide informed consent and to participate.

7. Known or suspected estrogen-dependent neoplasia, active neoplastic disease, history of breast cancer, or at risk of developing breast cancer, endometrial hyperplasia.

8. 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.

9. Thrombophlebitis, thrombosis, thromboembolic disorders, myocardial infarction, ischemic heart disease, cerebrovascular accident, stroke, transient ischemic attack (TIA).

10. Current use of tobacco or a history of alcohol abuse.

11. Use of drugs, herbs, or dietary supplements to treat menopausal or cognitive symptoms less than 8 weeks prior to baseline.

12. Evidence of any significant clinical disorder or laboratory finding.

13. Known allergy to soy-derived products/ proteins or branded over the counter products; hypersensitivity to estrogens or progestins.

14. Visual and auditory acuity inadequate for neuropsychological testing

15. Inability to undergo MRI scans

16. Inability to undergo PET scans

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Cornell University

OTHER

Sponsor Role: collaborator

ADM Diagnostics

UNKNOWN

Sponsor Role: collaborator

Roberta Brinton

OTHER

Sponsor Role: lead

Responsible Party

Roberta Brinton

Regents Professor and Director of the Center for Innovation in Brain Science

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Roberta D Brinton, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

Gerson D Hernandez, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

Locations

The Alzheimer's Prevention Program / Weill Cornell Medicine

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Claudia M Lopez, BS

Role: CONTACT

claudiml@arizona.edu

5206266276

Facility Contacts

Schantel Williams, MPH, RN

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 28926513 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30889096 (View on PubMed)

Other Identifiers

R01AG075122

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Phyto-2022-01

Identifier Type: -

Identifier Source: org_study_id