MenopausePhase 2NCT05664477

PhytoSERM to Prevent Menopause Associated Decline in Brain Metabolism and Cognition

A Phase 2 study testing PhytoSERM in people with Menopause and Cognitive Change, run by Roberta Brinton at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 45 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Menopause, Cognitive Change, Brain Disorder, Metabolic
What is being tested?: PhytoSERM
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 100 participants
Where: 2 sitesUnited States
Study dates: 10 Jan 2024to 31 Jan 2027
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 45 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Show all 12Show fewer

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.

Who cannot join

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.

Show all 16Show fewer

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
Inability to undergo PET scans

Trial locations and contacts

2 sites in 1 country.

United States2 sites

The Alzheimer's Prevention Program / Weill Cornell Medicine
New York, New York, 10021
University of Arizona / Clinical & Translational Sciences Research Center (CATS
Tucson, Arizona, 85721

Other trials in United States

About this study

Official title: PhytoSERM Efficacy to Prevent Menopause Associated Decline in Brain Metabolism and Cognition: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Clinical Trial

Read the 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
Being tested: PhytoSERM, Placebo
Medical subject headings: Brain Diseases, Metabolic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PhytoSERMDietary 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%).
PlaceboDrug
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.

Study groups in NCT05664477
Study group	Role	What they receive
PhytoSERM group	Experimental	PhytoSERM 50mg tablet composed of the phytoestrogens daidzein, genistein and S-equol, administered orally every day for 24 weeks. Receives: 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. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Standardized uptake value ratio (SUVR) by 18F-FDG PET
Regional brain glucose metabolism SUVR
Measured: Baseline to 24 weeks

Secondary outcomes (14)

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.
Measured: 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.
Measured: Baseline to 24 weeks
Picture Sequence Memory Test
Maximum raw score of 48 for ages 20-60 years. More is better.
Measured: 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).
Measured: 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).
Measured: Baseline to 24 weeks
Hot flash Frequency Composite
Hot flash frequency and severity scores. Less is better.
Measured: Baseline to 24 weeks
Menopause Rating Scale (MRS) Score
The total score of the MRS ranges between 0 (asymptomatic) and 44 (highest degree of complaints).
Measured: Baseline to 24 weeks
Pittsburgh Sleep Quality Index
A global sum of "5" or greater indicates a "poor" sleeper.
Measured: 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.
Measured: Baseline to 24 weeks
Beck Depression Inventory - II
Maximum score is 63. Higher scores represent greater depressive symptoms.
Measured: Baseline to 24 weeks
Pharmacokinetics: Peak Plasma Concentration (Cmax)
The highest concentration of each phytoestrogen in the blood after a dose is given.
Measured: Baseline
Pharmacokinetics: Time of peak concentration (tmax)
Time required to achieve peak plasma levels.
Measured: Baseline
Pharmacokinetics: Half-life (t1/2)
The time required for plasma concentration of phytoSERMs to decrease by 50%
Measured: 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.
Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Jan 202431 Jan 2027

First posted23 Dec 2022
Study start10 Jan 2024
Primary completion31 Jan 2027 (estimated)
Study completion31 Jan 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for MenopauseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 100 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05664477
Sponsor's protocol ID: Phyto-2022-01
Other IDs: R01AG075122
Status last verified: Mar 2026
First submitted: 8 Sep 2022
Last updated: 13 Mar 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Publications

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.
PubMed 28926513
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.
PubMed 30889096

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Hop Extract Versus Soy Isoflavone Extract for Menopausal Symptoms (HOPES)
Menopause, Perimenopause
Not yet recruiting
The Role of Diet Quality in Sleep Among Women in Postmenopause
Post Menopausal Women
Active, not recruitingPhase 3
Human Menopausal Gonadotropin Research in Infertility Assessing Cumulative Live Birth With Frozen Embryo Transfer.
Infertility (IVF Patients)
Not yet recruiting
Effect of Hormone Replacement Therapy on Physiotherapy Outcomes in Postmenopausal Women With Frozen Shoulder
Frozen Shoulder, Adhesive Capsulitis
RecruitingObservational study
Observational Study of Bone Complications in People With Post-menopausal Breast Cancer Who Have Stopped Treatment With Denosumab and Aromatase Inhibitors
Breast Cancer

All Menopause trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: PhytoSERM Efficacy to Prevent Menopause Associated Decline in Brain Metabolism and Cognition: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Clinical Trial
ClinicalTrials.gov ID: NCT05664477
Acronym / sponsor ID: Phyto-2022-01
Conditions: Menopause, Cognitive Change, Brain Disorder, Metabolic
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 100 participants (estimated)
Lead sponsor: Roberta BrintonUniversity, hospital or other
Collaborators: National Institute on Aging (NIA), Cornell University, ADM Diagnostics
Study start: 10 Jan 2024 (actual)
Primary completion: 31 Jan 2027 (estimated)
Study completion: 31 Jan 2027 (estimated)
First posted: 23 Dec 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
PhytoSERM group	Experimental	Dietary Supplement: PhytoSERMPhytoSERM 50mg tablet composed of the phytoestrogens daidzein, genistein and S-equol, administered orally every day for 24 weeks.
Placebo group	Placebo comparator	Drug: PlaceboPlacebo product with identical shape, size and color with absence of daidzein, genistein, and S-equol. Administered orally every day for 24 weeks.

Who may qualify

Ages: 45 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (12 listed)

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.

Key exclusion criteria (16 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PhytoSERMPhytoSERM 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%).	Dietary supplement	PhytoSERM group
PlaceboPlacebo 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.	Drug	Placebo group

Primary outcome

Standardized uptake value ratio (SUVR) by 18F-FDG PET
Time frame: Baseline to 24 weeks
Regional brain glucose metabolism SUVR

14 secondary outcomes

Trail Making Test (TMT)
Time frame: Baseline to 24 weeks
List Sorting Working Memory Test
Time frame: Baseline to 24 weeks
Picture Sequence Memory Test
Time frame: Baseline to 24 weeks
Auditory Verbal Learning Test
Time frame: Baseline to 24 weeks
Oral Symbol Digit Test
Time frame: Baseline to 24 weeks
Hot flash Frequency Composite
Time frame: Baseline to 24 weeks
Menopause Rating Scale (MRS) Score
Time frame: Baseline to 24 weeks
Pittsburgh Sleep Quality Index
Time frame: Baseline to 24 weeks
Positive and Negative Affect Scale
Time frame: Baseline to 24 weeks
Beck Depression Inventory - II
Time frame: Baseline to 24 weeks
Pharmacokinetics: Peak Plasma Concentration (Cmax)
Time frame: Baseline
Pharmacokinetics: Time of peak concentration (tmax)
Time frame: Baseline
Pharmacokinetics: Half-life (t1/2)
Time frame: Baseline
Pharmacokinetics: Area under the plasma concentration versus time curve (AUC)
Time frame: Baseline

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2026.
Background: PubMed 28926513Hernandez 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.
Background: PubMed 30889096Schneider 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.

Related trials for Menopause

Recruiting
Hop Extract Versus Soy Isoflavone Extract for Menopausal Symptoms (HOPES)
Menopause, Perimenopause
Not yet recruiting
The Role of Diet Quality in Sleep Among Women in Postmenopause
Post Menopausal Women
Active, not recruitingPhase 3
Human Menopausal Gonadotropin Research in Infertility Assessing Cumulative Live Birth With Frozen Embryo Transfer.
Infertility (IVF Patients)
Not yet recruiting
Effect of Hormone Replacement Therapy on Physiotherapy Outcomes in Postmenopausal Women With Frozen Shoulder
Frozen Shoulder, Adhesive Capsulitis
RecruitingObservational study
Observational Study of Bone Complications in People With Post-menopausal Breast Cancer Who Have Stopped Treatment With Denosumab and Aromatase Inhibitors
Breast Cancer

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Roberta D Brinton, PhD principal investigator

University of Arizona

Gerson D Hernandez, MD, MPH principal investigator

University of Arizona

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PhytoSERM in people with Menopause and Cognitive Change, run by Roberta Brinton at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 13 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Standardized uptake value ratio (SUVR) by 18F-FDG PET (time frame: Baseline to 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05664477, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2026.