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

Cardiometabolic Health Clinical Trial

— OPCT  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05414084
• Other study ID #: 1352/2020/SPER/UNIPR
• Status: Completed
• Phase: N/A
• Start date: May 31, 2022
• Est. completion date: May 26, 2023

Study information

• Verified date: February 2024
• Source: University of Parma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: May 26, 2023
• Est. primary completion date: May 26, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiometabolic Health

Intervention

Dietary Supplement:
• Oral (poly)phenol challenge test (OPCT)
Nutritional challenge with standardized (poly)phenol-rich tablets

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero-Universitaria di Parma	Parma	PR
Italy	University of Parma - Plesso Biotecnologico Integrato	Parma	PR

Sponsors (4)

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

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Assessing dietary habits	Dietary habits will be assessed through a food frequency questionnaire.	Baseline
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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