PhytoSERM for Menopause-related Cognitive Impairment

Overseen By Claudia M Lopez, BS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Arizona

Must not be taking: Estrogen, Progestin

Disqualifiers: Cognitive impairment, Breast cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a supplement called PhytoSERM to determine its effect on brain function in women undergoing or having completed menopause. Researchers aim to discover if this supplement alters how the brain uses energy compared to a placebo (a pill with no active ingredients). Women experiencing at least seven hot flashes a day and who have been without a menstrual period for 60 days to four years may be suitable for this study. The trial will assess whether PhytoSERM can safely and effectively improve cognitive symptoms related to menopause. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Will I have to stop taking my current medications?

The trial requires that your medications have been stable for at least 4 weeks before starting. If you are using estrogen or progestin compounds, or drugs, herbs, or supplements for menopausal or cognitive symptoms, you must stop them at least 8 weeks before starting the trial.

Is there any evidence suggesting that PhytoSERM is likely to be safe for humans?

Research has shown that PhytoSERM, a supplement made from plant-based compounds like daidzein, genistein, and S-equol, is safe for use. Studies have found that most people tolerate this supplement well. In research on its use for menopause symptoms and memory issues, no major safety problems emerged. Another study highlighted that PhytoSERM strongly interacts with a specific estrogen receptor, which might help protect brain cells. These findings support the idea that PhytoSERM is a safe choice for managing menopause symptoms. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for menopause-related cognitive impairment?

Unlike the standard treatments for menopause-related cognitive impairment, which typically involve hormone replacement therapy, PhytoSERM is derived from plant-based compounds known as phytoestrogens. This treatment includes the active ingredients daidzein, genistein, and S-equol, which mimic estrogen's effects without the use of synthetic hormones. Researchers are excited about PhytoSERM because it offers a potential alternative for those who cannot or prefer not to use traditional hormone therapies, possibly reducing associated risks while still providing cognitive benefits.

What evidence suggests that PhytoSERM might be an effective treatment for menopause-related cognitive impairment?

Research suggests that PhytoSERM, which contains natural compounds like genistein, daidzein, and S-equol, may improve brain function in postmenopausal women. These compounds mimic estrogen in the body. PhytoSERM targets a specific brain area that could support healthy brain cells. Some studies have shown that PhytoSERM can be a safe and effective alternative to traditional hormone therapy for managing menopause symptoms. This trial will compare PhytoSERM with a placebo to evaluate its potential benefits for brain health and memory in menopausal women. Overall, early findings are promising for PhytoSERM as a treatment for menopause-related memory issues. ^{1 2 4 6 7}

Who Is on the Research Team?

Roberta D Brinton, PhD

Principal Investigator

University of Arizona

Gerson D Hernandez, MD, MPH

Principal Investigator

University of Arizona

Are You a Good Fit for This Trial?

This trial is for peri- or postmenopausal women aged 45-60, experiencing hot flashes at least 7 times a day. Participants must be in good health, fluent in English/Spanish, and willing to follow the study procedures. They can't join if they've had recent cardiovascular issues, are pregnant, have used hormone treatments recently, or have certain cognitive impairments.

Inclusion Criteria

Your lab test results need to be normal, or if they're not, the doctor will decide if it's not a big problem.

I am not pregnant and will use effective birth control during the study.

No medical contraindications to study participation

Exclusion Criteria

I have never had epilepsy, severe head injuries, or major psychiatric disorders.

Use of investigational agent within 12 weeks of baseline

I do not have any significant health issues or abnormal lab results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive PhytoSERM or placebo orally every day for 24 weeks

24 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PhytoSERM
• Placebo

Trial Overview The trial tests PhytoSERM's safety and its effect on brain metabolism compared to a placebo in menopausal women. It measures changes using an imaging technique called 18F-FDG-PET that tracks glucose metabolism in the brain.

How Is the Trial Designed?

Group I: PhytoSERM group Experimental Treatment 1 Intervention

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

Group II: Placebo group Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

Roberta Brinton

Lead Sponsor

Trials

2

Recruited

110+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Cornell University

Collaborator

Trials

179

Recruited

14,090,000+

ADM Diagnostics

Collaborator

Trials

2

Recruited

300+

Published Research Related to This Trial

The phytoSERM formulation, which targets estrogen receptor-β, was well tolerated in a 12-week trial with 71 perimenopausal women, showing that both 50 mg and 100 mg daily doses were safe, with mild adverse events reported.

Despite some adverse effects, including mild vaginal bleeding, the 50 mg dose was preferred for further efficacy trials due to better safety outcomes and potential benefits on cognitive and vasomotor symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of estrogen receptor-β targeted phytoSERM formulation for menopausal symptoms: phase 1b/2a randomized clinical trial. Schneider, LS., Hernandez, G., Zhao, L., et al.[2023]

Estrogen-containing hormone therapy (HT) can provide health benefits for women within 10 years of menopause, but long-term use poses risks like breast cancer and stroke, highlighting the need for safer alternatives.

Research on soy-based isoflavones shows mixed results in improving cognitive function in postmenopausal women, suggesting that a standardized formulation and careful population selection could enhance therapeutic efficacy and provide benefits for both genders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

WHI and WHIMS follow-up and human studies of soy isoflavones on cognition. Zhao, L., Brinton, RD.[2007]

The use of 17 β-estradiol in menopausal women has been shown to reduce vasomotor symptoms and improve cognitive function, particularly in those with Alzheimer's disease.

Genistein, a flavonoid, may also help alleviate vasomotor symptoms and has potential neuroprotective effects, although more research is needed to fully understand its impact on cognition during menopause.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of the use of 17 β-estradiol and genistein in Alzheimer's disease in women with menopause]. Chávez-Pérez, C., Ceballos-Ramírez, A., Suárez-Castro, A.[2021]

The phytoestrogen formulation (phytoSERM) containing genistein, daidzein, and S-equol was well-tolerated in a study of 18 perimenopausal and postmenopausal women, with no reported adverse events after a single dose.

Pharmacokinetic analysis showed that the phytoSERM was rapidly absorbed, with plasma concentrations of the active compounds peaking at different times depending on the dose, indicating a clear dose-dependent response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety profile of single-dose administration of an estrogen receptor β-selective phytoestrogenic (phytoSERM) formulation in perimenopausal and postmenopausal women. Hernandez, G., Zhao, L., Franke, AA., et al.[2019]

The novel phyto-β-SERM formulation shows a strong preference for binding to the estrogen receptor subtype β (ERβ), which is linked to neuroprotective effects and alleviation of menopause-related symptoms, without causing feminizing effects in other body areas.

In a study with a female mouse model of Alzheimer's disease, a 9-month dietary supplementation with the phyto-β-SERM formulation improved physical health, memory, and reduced amyloid-β plaque formation, suggesting its potential as a preventive treatment for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early intervention with an estrogen receptor β-selective phytoestrogenic formulation prolongs survival, improves spatial recognition memory, and slows progression of amyloid pathology in a female mouse model of Alzheimer's disease. Zhao, L., Mao, Z., Chen, S., et al.[2021]

In a phase Ib/IIa trial involving 46 participants, PhytoSERM (50 mg daily) significantly reduced hot flash frequency compared to baseline and placebo, indicating its potential as a safe and effective treatment for menopause-related symptoms.

The study also suggested that genetic factors, such as mitochondrial haplogroup and APOE genotype, may influence the response to PhytoSERM, supporting a precision medicine approach for its further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective analysis of phytoSERM for management of menopause-associated vasomotor symptoms and cognitive decline: a pilot study on pharmacogenomic effects of mitochondrial haplogroup and APOE genotype on therapeutic efficacy. Wang, Y., Hernandez, G., Mack, WJ., et al.[2021]

The phytoestrogenic combination containing S-equol was found to be more effective than the R/S-equol combination in enhancing mitochondrial function and energy production in neuronal cultures and a mouse model of menopause.

Both phytoSERM combinations improved key bioenergetic pathways and did not induce any feminizing effects, suggesting their potential as safe nutraceuticals for alleviating menopause-related symptoms and promoting brain health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potentiation of brain mitochondrial function by S-equol and R/S-equol estrogen receptor β-selective phytoSERM treatments. Yao, J., Zhao, L., Mao, Z., et al.[2021]

A combination of phytoestrogens (genistein, daidzein, and equol) significantly enhances neural protective responses, showing a 30% increase in selectivity for the estrogen receptor beta (ERbeta) compared to individual phytoestrogens.

This combination not only improves neuronal survival and promotes defense mechanisms against neurodegeneration but also does not affect uterine growth, suggesting a safer alternative to conventional estrogen therapy for cognitive health in menopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A select combination of clinically relevant phytoestrogens enhances estrogen receptor beta-binding selectivity and neuroprotective activities in vitro and in vivo. Zhao, L., Mao, Z., Brinton, RD.[2009]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05664477

PhytoSERM to Prevent Menopause Associated Decline in ... 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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6663614/

Safety and feasibility of estrogen receptor β targeted ... PhytoSERM is a formulation of genistein, daidzein, and S-equol that has an 83-fold selective affinity for estrogen receptor-β (ERβ); and may enhance neuron ...

3. journals.lww.com journals.lww.com/menopausejournal/fulltext/2020/01000/retrospective_analysis_of_phytoserm_for_management.10.aspx

Retrospective analysis of phytoSERM ... Our data support a precision medicine approach for further development of PhytoSERM as a safe and effective alternative to hormone therapy for menopause- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7100617/

Retrospective Analysis of PhytoSERM for Management of ... Our data support a precision medicine approach for further development of PhytoSERM as a safe and effective alternative to hormone therapy for menopause ...

5. withpower.com withpower.com/trial/phase-2-brain-diseases-1-2023-901c8

PhytoSERM for Menopause-related Cognitive Impairment Research suggests that phytoestrogens like genistein, daidzein, and S-equol, which are components of PhytoSERM, may improve cognitive function in postmenopausal ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5771891/

Pharmacokinetics and safety profile of single-dose ... PhytoSERM, a preparation of genistein, daidzein, and S-equol, has an 83-fold selective affinity for estrogen receptor (ER) β and may promote neuronal survival ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06186531?term=daidzein&viewType=Table&rank=10

Study Details | PhytoSERM for Menopausal Hot Flashes ... This is a double-blinded, randomized, placebo-controlled, parallel designed, proof-of-concept phase 2 clinical trial to determine effect of PhytoSERM on ...