Aggregate Metabolic Phenotypes for (Poly)Phenols: Development of an Oral (Poly)Phenol Challenge Test (OPCT)

Sponsor

University of Parma (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05414084

Collaborator

Azienda Ospedaliero-Universitaria di Parma (Other), University of Birmingham (Other), Centro de Edafología y Biología Aplicada del Segura (CEBAS-CSIC) (Other)

300

Enrollment

Locations

Arm

Anticipated Duration (Months)

150

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Individual Variability in (Poly)Phenol Metabolism Cardiometabolic Health	Dietary Supplement: Oral (poly)phenol challenge test (OPCT)	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Screening

Official Title:

Identification of Aggregate Metabolic Phenotypes for the Main Dietary (Poly)Phenols and Assessment of the Factors Associated With Their Formation: Development of an Oral (Poly)Phenol Challenge Test (OPCT)

Anticipated Study Start Date :

May 31, 2022

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: (Poly)phenol tablets 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)	Dietary Supplement: Oral (poly)phenol challenge test (OPCT) Nutritional challenge with standardized (poly)phenol-rich tablets

Arm

Intervention/Treatment

Experimental: (Poly)phenol tablets

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)

Dietary Supplement: Oral (poly)phenol challenge test (OPCT)

Nutritional challenge with standardized (poly)phenol-rich tablets

Outcome Measures

Primary Outcome Measures

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

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.
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.
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.
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 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.
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 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.
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.
Assessing dietary habits [Baseline]
Dietary habits will be assessed through a food frequency questionnaire.
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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Adult (18-74 y)
BMI 18.5-35 kg/m^2

Exclusion Criteria:

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