Aggregate Metabolic Phenotypes for (Poly)Phenols: Development of an Oral (Poly)Phenol Challenge Test (OPCT)
- Conditions
- Cardiometabolic HealthIndividual Variability in (Poly)Phenol Metabolism
- Interventions
- Dietary Supplement: Oral (poly)phenol challenge test (OPCT)
- Registration Number
- NCT05414084
- Lead Sponsor
- University of Parma
- Brief Summary
The study is a single-dose acute clinical trial aiming at identifying aggregate metabolic phenotypes for the main dietary (poly)phenols and assessing the factors associated with their formation.
The treatment consists of a nutritional challenge representative of the consumption of (poly)phenols in Europeans (so-called oral (poly)phenol challenge test, OPCT) and foresees the supplementation of three standardized tablets rich in (poly)phenols, prepared from various commercially available plant extracts constituting sources of specific (poly)phenols. Urinary excretion of (poly)phenol metabolites will be evaluated at 24 hours after tablet consumption or, for two subgroups of volunteers, at different time points for 24 hours upon tablet consumption. Blood pressure and heart rate will also be measured and anthropometric data collected. Information will be collected on genetic polymorphisms related to the metabolism of (poly)phenols, gene expression, standard cardiometabolic health biomarkers, cardiometabolic risk scores and gut microbiota profile, through the collection of urine, blood and stool samples. Volunteers will follow a (poly)phenol-free diet before and after the OPCT. To check compliance with food restrictions, a 24-hour recall will be carried out on each visit. For a sub-group of 50 subjects, 3 months after the first challenge, the OPCT will be repeated with further urinary and fecal collection.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 300
- Adult (18-74 y)
- BMI 18.5-35 kg/m^2
- Past cardiovascular events and metabolic diseases including diabetes
- Inflammatory bowel diseases or gastro-intestinal surgery
- Renal (GFR<60 ml/min) or hepatic diseases (liver enzymes >2.5 fold higher)
- Immunodeficiency or autoimmune diseases (other than well-compensated hypothyroidism)
- Mental disorders
- Antibiotic therapy within the last month
- Food allergies
- Pregnancy or lactation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description (Poly)phenol tablets Oral (poly)phenol challenge test (OPCT) Single ingestion of 3 tablets containing different amounts of the most representative dietary (poly)phenols (i.e. flavonoid subclasses, phenolic acids, lignans, ellagitannins, stilbenes, flavonols, procyanidins and phenylethanoids)
- Primary Outcome Measures
Name Time Method Identification of aggregate phenolic metabotypes 24 hours post-consumption Assessing the variability in the urinary excretion of phenolic metabolites among volunteers after consumption of (poly)phenol-rich tablets by using data-driven clustering.
- Secondary Outcome Measures
Name Time Method Evaluating eicosanoids in urine samples Baseline Eicosanoids, including prostaglandins, thromboxanes, leukotrienes, isoprostanes and neuroprostanes will be evaluated in baseline urine samples (0-h) by UHPLC-QqQ-MS/MS.
Assessing transcriptomic signatures in peripheral blood mononuclear cells (PBMCs). Baseline Specific patterns of gene expression related to each metabotype will be investigated in PBMCs by using a microarray-based approach. Analysis will be carried out in a subset of 10 samples for each metabotype.
Evolution over the time of the phenolic metabolites in urine samples Different collection times for 24 hours (0; 0-3; 3-6; 6-9; 9-12; 12-24; 24 h) Assessed by using UHPLC-MS/MS for individual detection and quantification.
Assessing risk prediction scores Baseline Risk prediction scores (i.e., Framingham General Cardiovascular Risk Score, Framingham Heart Study Primary Risk Functions for heart disease, stroke, diabetes, fatty liver disease, and hypertension, Atherosclerotic Cardiovascular Disease (ASCVD) Risk, QRISK3®, QDScore®, Finnish Diabetes Risk Score (FINDRISC)) will be assessed to understand their relationship with the aggregate phenolic metabotypes observed. The higher the scores, the worse the risk of developing the disease.
Determining gut microbiota composition and functionality in fecal samples Baseline Microbial profiling will be assessed by shallow shotgun metagenomics. Full shotgun metagenomics analysis will be carried out to determine functional pathways in a sample subset (50 samples).
Untargeted urinary metabolomics Baseline and 24 hours post-consumption The untargeted LC-IMS-MS metabolomics approach will allow to assess potential differences among the metabolomes of individuals belonging to different aggregate phenolic metabotypes.
Assessing anthropometric measurements Baseline Weight and height will be combined to report BMI in kg/m\^2 and this will be carried out according to standardized procedures. Waist circumference and hip circumference, waist-to-height ratio, waist-to-hip ratio, and body composition measurement (skinfold test and bioelectrical impedance analysis).
Evaluating trimethylamine N-oxide (TMAO) in urine and plasma samples Baseline TMAO will be quantified in baseline urine and fasting plasma samples by UHPLC-MS/MS.
Assessing DNA oxidation catabolites and branched fatty acyl esters of hydroxyl fatty acids (FAHFAs) in plasma samples Baseline DNA oxidation catabolites and FAHFAs will be measured in fasting plasma samples by UHPLC-QqQ-MS/MS.
Assessing blood pressure and heart rate Baseline Systolic and diastolic blood pressure and heart rate of each volunteer will be obtained after a 5-min rest in a seated position in the baseline visit.
Assessing the stability of aggregate phenolic metabotypes among individuals after 3 months 24 hours post-consumption in a test carried out after 3 months after the first supplementation Assessing the variability in the urinary excretion of phenolic metabolites among volunteers after consumption of (poly)phenol-rich tablets, considering the metabotype to which each volunteer belongs to once the volunteer re-do the oral (poly)phenol challenge test after 3 months from the first supplementation.
Assessing common cardiometabolic health biomarkers in blood samples Baseline Samples will be processed for the analysis of common biomarkers of cardiometabolic health: total cholesterol (mg/dL), HDL-cholesterol (mg/dL), triglycerides (mg/dL), glucose (mg/dL), insuline (uUI/mL). Analyses will follow standardised routine procedures.
Determining genetic differences among subjects Baseline Genotyping will be conducted using genome wide, SNP array approach untargeted methodology, using commercially available SNP arrays and a tSNP approach. This approach will involve the genotyping of approximately 300 SNPs. Genomic DNA will be prepared from PBMCs isolated from blood samples.
Assessing dietary habits Baseline Dietary habits will be assessed through a food frequency questionnaire.
Trial Locations
- Locations (2)
University of Parma - Plesso Biotecnologico Integrato
🇮🇹Parma, PR, Italy
Azienda Ospedaliero-Universitaria di Parma
🇮🇹Parma, PR, Italy