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

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)

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.

Study Overview

• Status: Completed
• Conditions: Cardiometabolic Health; Individual Variability in (Poly)Phenol Metabolism
• Intervention / Treatment: Dietary supplement: Oral (poly)phenol challenge test (OPCT)

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pedro M Mena Parreño, PhD; Phone Number: +39 0521 903970; Email: pedromiguel.menaparreno@unipr.it
• Study Contact Backup: Name: Cristiana Mignogna, MSc; Phone Number: +39 0521 903841; Email: cristiana.mignogna@unipr.it

Study Locations

• Italy
  • PR
    • Parma, PR, Italy, 43126
      • Azienda Ospedaliero-Universitaria di Parma
    • Parma, PR, Italy, 43125
      • University of Parma - Plesso Biotecnologico Integrato

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 72 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of aggregate phenolic metabotypes	Assessing the variability in the urinary excretion of phenolic metabolites among volunteers after consumption of (poly)phenol-rich tablets by using data-driven clustering.	24 hours post-consumption

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing common cardiometabolic health biomarkers in blood samples	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.	Baseline
Assessing risk prediction scores	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.	Baseline
Evaluating trimethylamine N-oxide (TMAO) in urine and plasma samples	TMAO will be quantified in baseline urine and fasting plasma samples by UHPLC-MS/MS.	Baseline
Evaluating eicosanoids in urine samples	Eicosanoids, including prostaglandins, thromboxanes, leukotrienes, isoprostanes and neuroprostanes will be evaluated in baseline urine samples (0-h) by UHPLC-QqQ-MS/MS.	Baseline
Assessing DNA oxidation catabolites and branched fatty acyl esters of hydroxyl fatty acids (FAHFAs) in plasma samples	DNA oxidation catabolites and FAHFAs will be measured in fasting plasma samples by UHPLC-QqQ-MS/MS.	Baseline
Determining genetic differences among subjects	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.	Baseline
Assessing transcriptomic signatures in peripheral blood mononuclear cells (PBMCs).	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.	Baseline
Determining gut microbiota composition and functionality in fecal samples	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).	Baseline
Assessing dietary habits	Dietary habits will be assessed through a food frequency questionnaire.	Baseline
Assessing anthropometric measurements	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).	Baseline
Assessing blood pressure and heart rate	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.	Baseline
Evolution over the time of the phenolic metabolites in urine samples	Assessed by using UHPLC-MS/MS for individual detection and quantification.	Different collection times for 24 hours (0; 0-3; 3-6; 6-9; 9-12; 12-24; 24 h)
Untargeted urinary metabolomics	The untargeted LC-IMS-MS metabolomics approach will allow to assess potential differences among the metabolomes of individuals belonging to different aggregate phenolic metabotypes.	Baseline and 24 hours post-consumption
Assessing the stability of aggregate phenolic metabotypes among individuals after 3 months	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.	24 hours post-consumption in a test carried out after 3 months after the first supplementation

Collaborators and Investigators

• Sponsor: University of Parma
• Collaborators: University of Birmingham; Azienda Ospedaliero-Universitaria di Parma; Centro de Edafología y Biología Aplicada del Segura (CEBAS-CSIC)
• Investigators: Principal Investigator: Pedro M Mena Parreño, PhD, University of Parma

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2022
• Primary Completion (Actual): May 26, 2023
• Study Completion (Actual): May 26, 2023

Study Registration Dates

• First Submitted: May 26, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 10, 2022

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: intervention study; metabotypes; (poly)phenols; metabolic phenotypes; cardiometabolic diseases; inter-individual variability; phenolic metabolites
• Additional Relevant MeSH Terms: Anti-Infective Agents, Local; Anti-Infective Agents; Pharmaceutical Solutions; Disinfectants; Sclerosing Solutions; Phenol
• Other Study ID Numbers: 1352/2020/SPER/UNIPR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No