An interventional study of Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavones and Consumption of placebo in Menopause Related Conditions and Cardiovascular Risk, sponsored by National Research Council, Spain. Active, not recruiting at 1 site in Spain. Open to female participants aged 45 Years to 57 Years. Per ClinicalTrials.gov, last updated 2025-09-19.
Sponsored by National Research Council, Spain · Not applicable, Interventional, and Treatment
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.
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.
81 studies on the registry are indexed under Endotoxemia; 7 are open to participants now.
This study's enrollment of 90 is above the median of 31 across 70 interventional studies indexed under Endotoxemia.
Browse Endotoxemia studies →National Research Council, Spain is the lead sponsor of 28 studies on the registry; 1 is open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Consumption of polyphenol-rich plant extrats (PPs).
Dietary Supplement: Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavones
Consumption of microcrystalline cellulose (placebo).
Dietary Supplement: Consumption of placebo
Consumption of polyphenol-rich plant extracts (PPs).
Dietary Supplement: Capsules containing plant extracts, including resveratrol, ellagic acid and isoflavones
Consumption of microcrystalline cellulose (placebo).
Dietary Supplement: Consumption of placebo
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.).
Daily intake of three capsules (2.1 g/day) of microcrystalline cellulose for eight weeks
Oxidized LDL particles (LDLox)
15% change in serum oxidized LDL concentration (U/L) by ELISA
Time frame: Change from baseline at 8 weeks compared to placebo
Gut microbiome
Change in gut microbiome composition, including taxonomic relative abundance and α- and β-diversity indices, by shotgun metagenomic sequencing
Time frame: 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
Time frame: Change from baseline at 8 weeks compared to placebo
Blood lipids
Change in serum total cholesterol, LDLc and HDLc concentration (mg/dL) by autoanalyzer
Time frame: 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
Time frame: Change from baseline at 8 weeks compared to placebo
Lipopolysaccharide binding protein (LBP)
Change in serum LBP concentration (µg/ml) by ELISA
Time frame: 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.
Time frame: Change from baseline at 8 weeks compared to placebo
Short-chain fatty acids (SCFAs)
Change in fecal SCFA concentration (µM/g) by GC-MS
Time frame: Change from baseline at 8 weeks compared to placebo
Bile acids (BAs)
Change in fecal BA concentration (µM/g) by UPLC-QTOF-MS
Time frame: 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
Time frame: Change from baseline at 8 weeks compared to placebo
Untargeted metabolomics
Change in urinary metabolite concentrations (µg/mg creatinine) by UPLC-QTOF-MS
Time frame: 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
Time frame: 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
Time frame: Change from baseline at 8 weeks compared to placebo
Plan to share: 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.
Supporting information: Study protocol
Time frame: Time Frame: Beginning 12 months after publication of the results; available for 5 years.
Access criteria: Access Criteria: Qualified researchers may request access by contacting the Principal Investigator. Data will be shared in a controlled manner to ensure confidentiality of participants.
No publications or documents are linked to this record.
Ran from Jan 2024 to primary completion in Jul 2025, 17 months.
Of 29 non-industry interventional studies with no phase under Endotoxemia, half reached primary completion within 17 months of starting (the median), counting those still running; a quarter within 8 and three quarters within 25. This study's 17 months is close to that.
Counting every sponsor, half of 31 studies reached it within 17 months; a quarter within 8 and three quarters within 26.
How these figures are worked out, and which studies are left out of them.
This study is active, not recruiting, as verified in Sep 2025. You cannot join it, but the record below documents what was studied.
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National Research Council, Spain