Menopause Related ConditionsPolyPauseNCT07182370
Polyphenol Metabolism and Personalized Nutrition in Menopause (PolyPause).
A study testing Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavones in people with Menopause Related Conditions and Cardiovascular Risk, run by National Research Council, Spain at 1 site in Spain.
Trial summary
The study aims to evaluate the role of the gut microbiome and phageome in explaining interindividual variability in the metabolic response to polyphenol-rich nutraceuticals among menopausal women. Read more about this study
- Who is it for?
- Ages 45 to 57 years, women only
- Conditions the study is for
- Menopause Related Conditions, Cardiovascular Risk
- What is being tested?
- Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavones
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteSpain
- Study dates
- 15 Jan 2024to 31 Aug 2027
- Phase
- Interventional
- 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 57 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women aged 45 to 57 years.
- Diagnosed menopause (defined as 12 consecutive months without menstruation).
- Presenting at least one climacteric symptom (hot flashes and/or sweating episodes and/or low mood and/or irritability and/or decreased libido and/or insomnia and/or joint/muscle pain).
- Body Mass Index (BMI) ≥ 18 kg/m².
- Adequate cultural level and ability to understand the clinical study.
- Willing to voluntarily participate in the study and provide written informed consent.
Who cannot join
- Presence of severe, chronic-degenerative, or psychiatric conditions, or any contraindication to the use of nutritional supplements.
- History of major gastrointestinal surgery.
- Swallowing difficulties (e.g., inability to ingest capsules).
- BMI < 18 kg/m² or > 30 kg/m².
- Currently following a weight-loss regimen.
- Known or suspected allergy or intolerance to red clover extract, resveratrol (grape, wine), soy, or pomegranate.
Show all 14Show fewer
- Use of chronic preventive medication for cholesterol, glucose, blood pressure, etc. (e.g., statins, metformin, beta-blockers).
- Use of antibiotics within one month prior to study initiation.
- Undergoing hormone replacement therapy.
- Alcohol consumption exceeding 1 beer or 1 glass of wine per day.
- Regular use of dietary supplements (e.g., probiotics, isoflavones, resveratrol, others).
- Following a vegetarian diet.
- Current smoker or having smoked at any time during the past year.
- Individuals unwilling to comply with study guidelines.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Centro de Edafología y Biología Aplicada del Segura (CEBAS-CSIC)
Murcia, Murcia, 30100
About this study
Official title: Polyphenol Metabolism and Personalized Nutrition in Menopause: Metabotypes, Microbiome-virome, and Relationship With Quality of Life and Cardiovascular Risk.
The study aims to evaluate the role of the gut microbiome and phageome in explaining interindividual variability in the metabolic response to polyphenol-rich nutraceuticals among menopausal women. Insights from this research will support the development of personalized nutrition strategies to improve quality of life and reduce cardiovascular disease (CVD) risk during menopause.
Read the detailed description
This trial aims to investigate the role of the gut microbiome and phageome in mediating interindividual variability in the metabolic response to polyphenol-rich plant extracts among postmenopausal women. Polyphenols are widely recognized for their potential benefits in cardiovascular health, cognitive function, and overall metabolic regulation. However, the magnitude and direction of their effects vary significantly between individuals. Mounting evidence suggests that the gut microbiota plays a critical role in the biotransformation of polyphenols into bioactive metabolites, giving rise to the so-called gut microbiota metabotypes (i.e., metabolic fingerprints of the gut microbiota that produce specific metabolites depending on the individual), thereby modulating the physiological effects of ingested polyphenols.
A cohort of postmenopausal women will be studied at four timepoints in a randomized, double-blind, placebo-controlled, crossover trial. Participants will undergo a controlled dietary intervention with standardized polyphenol-rich plant extracts (pomegranate, soy, and resveratrol). The primary outcome will be a ≥15% change in serum oxidized LDL (oxLDL). At each timepoint, gut microbiome and phageome profiles will be characterized using shotgun metagenomic sequencing. TMAO, bile acids, and short-chain fatty acids will be determined by UPLC-QTOF-MS and GC-MS. Additional biomarkers of cardiovascular and metabolic health will be determined, including serum total cholesterol, LDLc, HDLc, and LPS-binding protein (LBP); fecal microbial enzymatic activities (β-glucuronidase and sulfatase); and serum neurotransmitters (GABA, dopamine, serotonin, melatonin, epinephrine, norepinephrine).
The distribution of polyphenol metabotypes in this cohort will be assessed through circulating and urinary phenolic-derived metabolites. This will allow exploration of differential individual responses to polyphenol intake and their derived health effects. Untargeted urinary metabolomics will further explore potential changes in metabolites relevant to cardiovascular prevention. Quality of life will be evaluated using the validated Cervantes Scales, which include domains related to menopause-associated symptoms, cognitive issues, and overall health.
The study is designed to integrate multi-omic data, combining microbial and phageomic composition with metabolomic and biochemical readouts, to identify patterns and predictors of individual responses to polyphenol intake. Statistical and bioinformatic analyses will focus on associations between microbiome/phageome signatures and metabolic outcomes, aiming to elucidate the mechanisms by which gut microbes and their viruses influence polyphenol biotransformation and subsequent systemic effects. This study therefore seeks to advance precision nutrition strategies for postmenopausal women. Insights gained may inform personalized dietary recommendations aimed at enhancing cardiovascular health, metabolic regulation, and overall quality of life during menopause. Moreover, the inclusion of the phageome represents a highly innovative and largely unexplored aspect of the study, offering new avenues for microbiota-targeted interventions.
Overall, this research will contribute to understanding the complex interactions between diet, the gut ecosystem, and human metabolism, ultimately supporting the development of evidence-based, individualized nutritional strategies to reduce cardiovascular disease risk and improve health outcomes in the postmenopausal population.
- Conditions
- Menopause Related Conditions, Cardiovascular Risk
- Being tested
- Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavones, Consumption of placebo
- Keywords
- Menopause, Microbiome, Phageome, Cardiovascular risk, Gut dysbiosis, Quality of life, LDLox, TMAO, Bile acids, Blood lipids, resveratrol, pomegranate, urolithin, isoflavones, equol, Metabotype, Personalized nutrition, Lunularin, Ellagic acid, Endotoxemia
- Medical subject headings
- Endotoxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavonesDietary supplement
Eight-week intake of three capsules per day, containing a total of 2.1 g of plant extracts (PPs), including 150 mg of resveratrol (found in grapes and red wine), 100 mg of ellagic acid (present in strawberries, walnuts, pomegranate, etc.), and 50 mg of the isoflavone daidzein, among others (found in soy, red clover, etc.).
Consumption of placeboDietary supplement
Daily intake of three capsules (2.1 g/day) of microcrystalline cellulose for eight weeks
| Study group | Role | What they receive |
|---|---|---|
| Polyphenol-rich capsules (PPs-A) | Experimental | Consumption of polyphenol-rich plant extrats (PPs). Receives: Dietary Supplement: Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavones |
| (Placebo-A) | Placebo comparator | Consumption of microcrystalline cellulose (placebo). Receives: Dietary Supplement: Consumption of placebo |
| Polyphenol-rich capsules (PPs-B) | Experimental | Consumption of polyphenol-rich plant extracts (PPs). Receives: Dietary Supplement: Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavones |
| (Placebo-B) | Placebo comparator | Consumption of microcrystalline cellulose (placebo). Receives: Dietary Supplement: Consumption of placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oxidized LDL particles (LDLox)
15% change in serum oxidized LDL concentration (U/L) by ELISA
Measured: Change from baseline at 8 weeks compared to placebo
Secondary outcomes (12)
Gut microbiome
Change in gut microbiome composition, including taxonomic relative abundance and α- and β-diversity indices, by shotgun metagenomic sequencing
Measured: Change from baseline at 8 weeks compared to placebo
Gut phageome
Change in gut phageome composition, including taxonomic relative abundance and α- and β-diversity indices, by shotgun metagenomic sequencing
Measured: Change from baseline at 8 weeks compared to placebo
Blood lipids
Change in serum total cholesterol, LDLc and HDLc concentration (mg/dL) by autoanalyzer
Measured: Change from baseline at 8 weeks compared to placebo
Trimethylamine N-oxide (TMAO)
Change in serum (µM) and urine (µM/mg creatinine) TMAO concentration by UPLC-QTOF-MS
Measured: Change from baseline at 8 weeks compared to placebo
Lipopolysaccharide binding protein (LBP)
Change in serum LBP concentration (µg/ml) by ELISA
Measured: Change from baseline at 8 weeks compared to placebo
Quality of life (Cervantes Scale)
Changes in the domains of the Cervantes Scale (validated questionnaires): Health, psychological, sexuality, and couple relationship.
Measured: Change from baseline at 8 weeks compared to placebo
Short-chain fatty acids (SCFAs)
Change in fecal SCFA concentration (µM/g) by GC-MS
Measured: Change from baseline at 8 weeks compared to placebo
Bile acids (BAs)
Change in fecal BA concentration (µM/g) by UPLC-QTOF-MS
Measured: Change from baseline at 8 weeks compared to placebo
Change in serum neurotransmitters
Change in serum gamma-aminobutyric acid (GABA, µM), serotonin, melatonin, dopamine, epinephrine, and norepinephrine (nM) by UPLC-QTOF-MS
Measured: Change from baseline at 8 weeks compared to placebo
Untargeted metabolomics
Change in urinary metabolite concentrations (µg/mg creatinine) by UPLC-QTOF-MS
Measured: Change from baseline at 8 weeks compared to placebo
Gut microbiota metabotypes
Distribution of urolithin, equol, and resveratrol metabotypes in postmenopausal women by UPLC-QTOF-MS metabolite profiling
Measured: Identification at baseline and after 8 weeks consuming the polyphenol-rich plant extracts
Estrobolome activity
Change in fecal microbial glucuronidase and sulfatase activities (U/mg protein) by spectrophotometry
Measured: Change from baseline at 8 weeks compared to placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2025
- Study start15 Jan 2024
- Primary completion1 Jul 2025
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Menopause Related ConditionsStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Crossover Assignment. Randomized, double-blind, placebo-controlled and crossover trial.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Research Council, Spain
- Sponsor type
- Other government
- Collaborators
- Hospital Universitario Virgen de la Arrixaca, IMDEA Food
- Responsible party
- Principal investigator, Juan Carlos Espín de Gea, National Research Council, Spain
- Investigators
- Juan C. Espín, PhD, Principal investigator, Spanish National Research Council
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07182370
- Sponsor's protocol ID
- PID2022-136419OB-I00
- Acronym
- PolyPause
- Status last verified
- Sep 2025
- First submitted
- 2 Sep 2025
- Last updated
- 19 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying the results (including raw metabolomics datasets from UPLC-QTOF-MS and GC-MS, and raw microbiome/phageome sequencing data) will be available upon reasonable request. Data will be shared after publication of the primary outcomes and will require a data use agreement to ensure appropriate use.
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Polyphenol Metabolism and Personalized Nutrition in Menopause: Metabotypes, Microbiome-virome, and Relationship With Quality of Life and Cardiovascular Risk.
- ClinicalTrials.gov ID
- NCT07182370
- Acronym / sponsor ID
- PolyPause / PID2022-136419OB-I00
- Conditions
- Menopause Related Conditions, Cardiovascular Risk
- Keywords
- Menopause, Microbiome, Phageome, Cardiovascular risk, Gut dysbiosis, Quality of life, LDLox, TMAO
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 90 participants (actual)
- Lead sponsor
- National Research Council, SpainOther government
- Collaborators
- Hospital Universitario Virgen de la Arrixaca, IMDEA Food
- Study start
- 15 Jan 2024 (actual)
- Primary completion
- 1 Jul 2025 (actual)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 19 Sep 2025 (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.
The study aims to evaluate the role of the gut microbiome and phageome in explaining interindividual variability in the metabolic response to polyphenol-rich nutraceuticals among menopausal women. Insights from this research will support the development of personalized nutrition strategies to improve quality of life and reduce cardiovascular disease (CVD) risk during menopause.
Detailed description
This trial aims to investigate the role of the gut microbiome and phageome in mediating interindividual variability in the metabolic response to polyphenol-rich plant extracts among postmenopausal women. Polyphenols are widely recognized for their potential benefits in cardiovascular health, cognitive function, and overall metabolic regulation. However, the magnitude and direction of their effects vary significantly between individuals. Mounting evidence suggests that the gut microbiota plays a critical role in the biotransformation of polyphenols into bioactive metabolites, giving rise to the so-called gut microbiota metabotypes (i.e., metabolic fingerprints of the gut microbiota that produce specific metabolites depending on the individual), thereby modulating the physiological effects of ingested polyphenols.
A cohort of postmenopausal women will be studied at four timepoints in a randomized, double-blind, placebo-controlled, crossover trial. Participants will undergo a controlled dietary intervention with standardized polyphenol-rich plant extracts (pomegranate, soy, and resveratrol). The primary outcome will be a ≥15% change in serum oxidized LDL (oxLDL). At each timepoint, gut microbiome and phageome profiles will be characterized using shotgun metagenomic sequencing. TMAO, bile acids, and short-chain fatty acids will be determined by UPLC-QTOF-MS and GC-MS. Additional biomarkers of cardiovascular and metabolic health will be determined, including serum total cholesterol, LDLc, HDLc, and LPS-binding protein (LBP); fecal microbial enzymatic activities (β-glucuronidase and sulfatase); and serum neurotransmitters (GABA, dopamine, serotonin, melatonin, epinephrine, norepinephrine).
The distribution of polyphenol metabotypes in this cohort will be assessed through circulating and urinary phenolic-derived metabolites. This will allow exploration of differential individual responses to polyphenol intake and their derived health effects. Untargeted urinary metabolomics will further explore potential changes in metabolites relevant to cardiovascular prevention. Quality of life will be evaluated using the validated Cervantes Scales, which include domains related to menopause-associated symptoms, cognitive issues, and overall health.
The study is designed to integrate multi-omic data, combining microbial and phageomic composition with metabolomic and biochemical readouts, to identify patterns and predictors of individual responses to polyphenol intake. Statistical and bioinformatic analyses will focus on associations between microbiome/phageome signatures and metabolic outcomes, aiming to elucidate the mechanisms by which gut microbes and their viruses influence polyphenol biotransformation and subsequent systemic effects. This study therefore seeks to advance precision nutrition strategies for postmenopausal women. Insights gained may inform personalized dietary recommendations aimed at enhancing cardiovascular health, metabolic regulation, and overall quality of life during menopause. Moreover, the inclusion of the phageome represents a highly innovative and largely unexplored aspect of the study, offering new avenues for microbiota-targeted interventions.
Overall, this research will contribute to understanding the complex interactions between diet, the gut ecosystem, and human metabolism, ultimately supporting the development of evidence-based, individualized nutritional strategies to reduce cardiovascular disease risk and improve health outcomes in the postmenopausal population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 4
- Model description
- Crossover Assignment. Randomized, double-blind, placebo-controlled and crossover trial.
| Arm | Type | Receives |
|---|---|---|
| Polyphenol-rich capsules (PPs-A) | Experimental | Dietary Supplement: Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavonesConsumption of polyphenol-rich plant extrats (PPs). |
| (Placebo-A) | Placebo comparator | Dietary Supplement: Consumption of placeboConsumption of microcrystalline cellulose (placebo). |
| Polyphenol-rich capsules (PPs-B) | Experimental | Dietary Supplement: Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavonesConsumption of polyphenol-rich plant extracts (PPs). |
| (Placebo-B) | Placebo comparator | Dietary Supplement: Consumption of placeboConsumption of microcrystalline cellulose (placebo). |
Who may qualify
- Ages
- 45 to 57 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Women aged 45 to 57 years.
- Diagnosed menopause (defined as 12 consecutive months without menstruation).
- Presenting at least one climacteric symptom (hot flashes and/or sweating episodes and/or low mood and/or irritability and/or decreased libido and/or insomnia and/or joint/muscle pain).
- Body Mass Index (BMI) ≥ 18 kg/m².
- Adequate cultural level and ability to understand the clinical study.
Key exclusion criteria (14 listed)
- Presence of severe, chronic-degenerative, or psychiatric conditions, or any contraindication to the use of nutritional supplements.
- History of major gastrointestinal surgery.
- Swallowing difficulties (e.g., inability to ingest capsules).
- BMI < 18 kg/m² or > 30 kg/m².
- Currently following a weight-loss regimen.
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 |
|---|---|---|
| Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavonesEight-week intake of three capsules per day, containing a total of 2.1 g of plant extracts (PPs), including 150 mg of resveratrol (found in grapes and red wine), 100 mg of ellagic acid (present in strawberries, walnuts, pomegranate, etc.), and 50 mg of the isoflavone daidzein, among others (found in soy, red clover, etc.). | Dietary supplement | Polyphenol-rich capsules (PPs-A), Polyphenol-rich capsules (PPs-B) |
| Consumption of placeboDaily intake of three capsules (2.1 g/day) of microcrystalline cellulose for eight weeks | Dietary supplement | (Placebo-A), (Placebo-B) |
Primary outcome
Oxidized LDL particles (LDLox)
Time frame: Change from baseline at 8 weeks compared to placebo
15% change in serum oxidized LDL concentration (U/L) by ELISA
12 secondary outcomes
Gut microbiome
Time frame: Change from baseline at 8 weeks compared to placebo
Gut phageome
Time frame: Change from baseline at 8 weeks compared to placebo
Blood lipids
Time frame: Change from baseline at 8 weeks compared to placebo
Trimethylamine N-oxide (TMAO)
Time frame: Change from baseline at 8 weeks compared to placebo
Lipopolysaccharide binding protein (LBP)
Time frame: Change from baseline at 8 weeks compared to placebo
Quality of life (Cervantes Scale)
Time frame: Change from baseline at 8 weeks compared to placebo
Short-chain fatty acids (SCFAs)
Time frame: Change from baseline at 8 weeks compared to placebo
Bile acids (BAs)
Time frame: Change from baseline at 8 weeks compared to placebo
Change in serum neurotransmitters
Time frame: Change from baseline at 8 weeks compared to placebo
Untargeted metabolomics
Time frame: Change from baseline at 8 weeks compared to placebo
Gut microbiota metabotypes
Time frame: Identification at baseline and after 8 weeks consuming the polyphenol-rich plant extracts
Estrobolome activity
Time frame: Change from baseline at 8 weeks compared to placebo
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 19 Sep 2025.
- Individual participant dataSharing planned: Yes. De-identified individual participant data underlying the results (including raw metabolomics datasets from UPLC-QTOF-MS and GC-MS, and raw microbiome/phageome sequencing data) will be available upon reasonable request. Data will be shared after publication of the primary outcomes and will require a data use agreement to ensure appropriate use.
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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.
Juan C. Espín, PhD principal investigator
Spanish National Research Council
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavones in people with Menopause Related Conditions and Cardiovascular Risk, run by National Research Council, Spain at 1 site in Spain.
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 6 inclusion and 14 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 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. 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.
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?
Oxidized LDL particles (LDLox) (time frame: Change from baseline at 8 weeks compared to placebo). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Sep 2025; AzTrials last refreshed its copy on 26 Oct 2026.