PhytoSERM for Menopausal Hot Flashes and Sustained Brain Health (HF-Relief)

PhytoSERM for Menopausal Hot Flashes and Sustained Brain Health: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Clinical Trial

This is a proof-of-concept phase 2 clinical trial to investigate the effect of the phytoestrogenic supplement PhytoSERM on vasomotor symptoms and other symptoms associated with the menopausal transition, and on blood-based biomarkers in peri- and postmenopausal women.

After the screening period, participants will be randomized to PhytoSERM 50 mg pills (administered orally, once per day) or matching placebo, 1:1 allocation, for a period of 12 weeks. After 12 weeks, all participants in the placebo group will be crossed-over to receive PhytoSERM pills for the remainder of the study (open-label phase).

Study Overview

• Status: Recruiting
• Conditions: Hot Flashes; Menopause
• Intervention / Treatment: Dietary supplement: PhytoSERM; Drug: Placebo

Detailed Description

This is a double-blinded, randomized, placebo-controlled, parallel designed, proof-of-concept phase 2 clinical trial to determine effect of PhytoSERM on vasomotor symptoms and other symptoms associated with the menopausal transition. PhytoSERM or placebo pills will be administered orally once a day over 24 weeks. Safety and tolerability will also be assessed over the duration of the study.

A total of 132 peri- or postmenopausal women aged 45-60 years and who are experiencing hot flashes will be enrolled in this trial. To determine eligibility, all participants will undergo cognitive assessment, physical assessment, ECG, clinical/safety laboratory assessment, and interviews. After a 2-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. After 12 weeks, participants in the placebo group will be crossed-over to PhytoSERM 50 mg for the remaining 12 weeks (open-label extension period). Hot flashes will be measured both objectively and subjectively. Objective data will be skin conductance levels collected via a wearable device that enables real-time physiological data acquisition, including activity and sleep data. Study participants will be asked to complete a total of 8 study visits. Study visits will occur at 4-week intervals after the baseline, except for visits # 6 and 7 (open-label period) which will occur at 6-week intervals after visit # 5 (final outcomes assessments visit). Visits 1, 2, 5 and 7 will last approximately 2-4 hours; visits 3, 4, 6 and 8 will last approximately 45 minutes.

All participants will be enrolled at a single site, at the University of Arizona (UA) Clinical & Translational Sciences Research Center (CATS).

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Claudia M Lopez, BSc; Phone Number: 520-626-6276; Email: claudiml@arizona.edu

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Recruiting
      • University of Arizona
      • Contact: Claudia M Lopez, BSc; Phone Number: 520-626-6276; Email: claudiml@arizona.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Peri- or postmenopausal women, defined by any of the following:

  1. Last menstrual period (LMP) completed ≥ 60 days and ≤ 8 years, per the Stages of Reproductive Aging Workshop (STRAW) criteria.
  2. Post-hysterectomy or endometrial ablation ≥ 3 months and supported by FSH levels.
• Age 45-60 years.
• Presence of hot flashes ≥ 7 per day.
• Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be not clinically significant by the investigator.
• Mammogram within normal limits in the past 2 years: Breast Imaging Reporting and Data System (BI-RADS) category 1-2 or 3 with findings stable for 3 years.
• No medical contraindications to study participation.
• Stable medications for 4 weeks prior to the baseline visits.
• 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.

Exclusion Criteria:

• Use of isoflavone containing supplements.
• Known allergies to isoflavones or soy-based products.
• Montreal Cognitive Assessment total score < 22.
• 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 (breast, ovarian and uterine cancers), active neoplastic disease, history of breast cancer, and endometrial hyperplasia.
• History within the last 5 years of any other primary or recurrent malignant disease, with the exception of resected cutaneous squamous cell carcinoma in situ, and basal cell carcinoma.
• History of epilepsy, focal brain lesion, head injury with loss of consciousness or 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, TIA.
• Current use of tobacco or a history of alcohol abuse.
• Use of anticoagulants.
• Chronic use of most benzodiazepines
• Use of drugs, herbs, or dietary supplements to treat menopausal or cognitive symptoms less than 8 weeks prior to baseline (e.g., SSRIs, rhubarb, red clover, licorice, kudzu, black cohosh, ginseng or other similar roots, etc.)
• Evidence of any significant clinical disorder or laboratory finding, including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine, metabolic, renal, or other systemic disease or laboratory abnormality.
• Known allergy to soy-derived products/ proteins or branded over the counter products; hypersensitivity to estrogens or progestins.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PhytoSERM; Active intervention group	Dietary supplement: PhytoSERM; PhytoSERM, a formulated dietary supplement, will be an ovalized tablet measuring 8.51 mm x 15.49 mm. Each pill will contain a white PEG coating and an equal mixture of, daidzein, genistein, and S-equol.
Placebo Comparator: Placebo group; Control group	Drug: Placebo; Placebo product is of identical shape, size and color with a white PEG coating but without S-equol, daidzein and genistein.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hot Flash Composite score	Composite score comprised by hot flash frequency and severity (sum of weekly hot flashes weighted by severity: mild, moderate, severe). Higher score indicates a bad outcome. No minimum or maximum values.	Daily from baseline to week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trail Making Test score	Test that involves visual scanning and working memory. Score is the amount of seconds taken to complete the test; the greater the time the worse the score.	Baseline, week 4, 8, 12 and 24.
NIH Toolbox List Sorting Working Memory Test score	An assessment of working memory administered on an iPad. Scores range from 0 to 26, with higher being better.	Baseline, week 4, 8, 12 and 24.
NIH Toolbox Picture Sequence Memory Test	An assessment of episodic memory administered on an iPad. The participants are asked to recall the sequence of pictures demonstrated over two learning trials; sequence length varies from 6-18 pictures. Participants are given credit for each adjacent pair of pictures they correctly place up to the maximum value for the sequence, which is one less than the sequence length. Range is 0-17.	Baseline, week 4, 8, 12 and 24.
NIH Toolbox Auditory Verbal Learning Test	An assessment of immediate memory and verbal learning administered on an iPad.Possible range is 0-45 words, with higher scores representing better performance.	Baseline, week 4, 8, 12 and 24.
NIH Toolbox Oral Symbol Digit Test	An assessment of processing speed administered on an iPad. Scored as the number of items answered correctly in 120 seconds (possible range is 0-144).	Baseline, week 4, 8, 12 and 24.
Pittsburgh Sleep Quality Index (PSQI)	Instrument used to measure the quality patterns of sleep in the older adult. A global sum of "5" or greater indicates a "poor" sleeper.	Baseline, week 4, 8, 12, 18, 24 and 28.
Menopause Rating Scale score	A a health-related quality of life scale measuring the impact of menopausal symptoms. The total score of the MRS ranges between 0 (asymptomatic) and 44 (highest degree of complaints).	At screening, weeks 12, 24 and 28.
Bone Mineral Density (BMD)	BMD in g/cm2 will be measured with a Dual-energy X-ray absorptiometry (DXA) scan. Expected range is 0.5-1.5 g/cm2, with higher being better.	Baseline, week 12 and 24
Bone Mineral Content (BMC)	BMC in grams will be measured with a Dual-energy X-ray absorptiometry (DXA) scan. Expected range is 2,000 - 3,500 g, with higher being better.	Baseline, week 12 and 24
Body Mass Index (BMI)	BMI will be measured with a Dual-energy X-ray absorptiometry (DXA) scan. Range is 10-45.	Baseline, week 12 and 24
Total Fat Mass (TFM)	TFM in grams will be measured with a Dual-energy X-ray absorptiometry (DXA) scan.	Baseline, week 12 and 24
Total Lean Mass (TLM)	TLM in grams will be measured with a Dual-energy X-ray absorptiometry (DXA) scan.	Baseline, week 12 and 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Digital hot flash frequency	Skin conductance levels measured via electrodermal activity (EDA) sensors will be used as an objective physiological measure of hot flashes.	Daily from baseline to week 28.
Follicle-Stimulating Hormone (FSH) levels	Reproductive hormone / menopause biomarker	Baseline, weeks 12 and 24
Estrodiol levels	Reproductive hormone / menopause biomarker	Baseline, weeks 12 and 24
Cholesterol levels	Metabolic biomarker	Baseline, weeks 12 and 24
Trigliceryde levels	Metabolic biomarker	Baseline, weeks 12 and 24
HbA1C levels	Metabolic biomarker	Baseline, weeks 12 and 24
Aß40:Aß42 ratio	Alzheimer's biomarker	Baseline, weeks 12 and 24
Glial fibrillary acidic protein (GFAP) levels	Neuroinflammation biomarker	Baseline, weeks 12 and 24
Neurofilament Light (NfL) levels	Neurodegeneration biomarker	Baseline, weeks 12 and 24

Collaborators and Investigators

• Sponsor: NeuTherapeutics
• Collaborators: University of Arizona
• Investigators: Study Director: Gerson D Hernandez, MD, MPH, University of Arizona; Principal Investigator: Fei Yin, PhD, University of Arizona

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2023
• Primary Completion (Estimated): November 15, 2024
• Study Completion (Estimated): November 15, 2024

Study Registration Dates

• First Submitted: November 30, 2023
• First Submitted That Met QC Criteria: December 15, 2023
• First Posted (Estimated): January 1, 2024

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Hot flashes; Menopause; Cognition; Phytoestrogen supplement
• Additional Relevant MeSH Terms: Hot Flashes
• Other Study ID Numbers: Phyto-HF-2022-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No