Investigation of in Vivo Endogenous and/or Exogenous Production of Phenolic Metabolites Using (un)Targeted Metabolomics

NCT06028659 | Recruiting

• 1 other identifier: 340/2023/SPER/UNIPR
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Plant (poly)phenols is what we call a large number of substances that are produced by plants as secondary plant metabolites, which means substances that are not used for their growth and development but are necessary for them to survive. (Poly)phenols are divided in two major groups, flavonoids, and non-flavonoids, and each group contains a varied set of subgroups and substances. They are widely spread in fruit and vegetables that are part of the human diet, and, in general, studies have attributed many biological effects to the ingestion of (poly)phenols, especially in the prevention of non-communicable diseases. For this reason, research aims to understand their role in the health benefits of a diet that is rich in fruits and vegetables. When ingested, (poly)phenols are digested by both the human organism and the gut microbiota and are broken down into several smaller substances (catabolites) that are called low-molecular weight (poly)phenols (LMWP). Most of the absorbed (poly)phenols that reach our bloodstream and organs are LMWP. For the proposed study, 30 healthy adults will be recruited and, if considered able to participate, will follow a standardized diet that is restricted in (poly)phenol intake and will be randomly divided into two groups: one will receive a known source of (poly)phenols (coffee) and the other will receive water, keeping the restriction of (poly)phenol from the diet. The duration of one phase is 4 days + 12 hours, during which urine, feces, and saliva will be collected. Then, after a 2-week-interval, subjects will repeat the experiment, except that this time the group who had coffee will have water, and vice versa. Again, urine and feces will be collected. The objective of the study is to identify and quantify LMWP mainly in urine, but also in feces, and try to understand how much was produced when there was no (poly)phenols in the diet compared with when there was ingestion of coffee (poly)phenols. The production of LMWP without coffee could be because of their production from other sources, like the metabolism of amino acids, proteins, and catecholamines (i.e. dopamine). The composition of the gut microbiota and relevant genetic information can alter the metabolism of (poly)phenols and will be considered in the analyses. Knowing how much of LMWP actually comes from the diet is important to understand the relevance and health benefits of these molecules.

Conditions

Individual Variability in (Poly)Phenol Metabolism

Keywords

(poly)phenols; catabolites; coffee; metabolism; low-molecular-weight (poly)phenols; metabolomics

Outcome Measures

Primary Outcomes (1)

• Number and concentration of phenolic metabolites in urine

  Urine samples will be subjected to both targeted and untargeted liquid chromatography mass spectrometry analyses

  Samples acquired from 60 hours prior to 48 hours after intervention or control

Secondary Outcomes (4)

• Identification and quantification of gut bacteria (genera and species) in feces

  Samples acquired from 6-48 hours after coffee or control

• Number and concentration of phenolic metabolites in feces

  Samples acquired from 6-48 hours after coffee or control

• Identification and quantification of metabolites after in vitro fecal fermentation

  Samples acquired from 6-48 hours after coffee or control

• Identification of single-nucleotide polymorphism analysis

  Single saliva samples collected from 1 hour to 30 minutes before the intervention with coffee or control.

Study Arms (2)

Coffee

EXPERIMENTAL

In this arm, volunteers will receive, once, 3 decaffeinated coffees (150 mL total) with sugar as a known source of (poly)phenols.

Other: Coffee

Control

OTHER

In this arm, volunteers will receive, once, 150 mL of sugared water as control.

Other: Water

Interventions

Coffee OTHER

Decaffeinated coffee with 1 pack (5g) of sugar from commercially available brands prepared with commercially available domestic coffee machines.

Coffee

Water OTHER

150 mL of hot water with 1 pack (5g) of sugar from commercially available brands prepared with commercially available domestic coffee machines.

Control

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Apparently healthy adults,
• Age 20-40 years old,
• Body mass index (BMI) between 18-28,
• Regular coffee consumers (at least 1 cup a day).

You may not qualify if:

• Clinical diagnosis of metabolic diseases,
• Clinical diagnosis of cardiovascular diseases,
• Clinical diagnosis of renal diseases,
• Clinical diagnosis of digestive diseases,
• Immunodeficiency
• Autoimmune diseases (other than well-compensated hypothyroidism),
• Mental disorders
• Regular use of medication (except birth-control pills and hormone replacement therapies),
• Use of antibiotics in the last month prior to enrollment,
• Food allergies or intolerances,
• Pregnancy
• Lactation

Sponsors & Collaborators

• University of Parma: lead

Study Sites (1)

University of Parma - Plesso Biotecnologico Integrato

Parma, PR, 43125, Italy

RECRUITING

Related Publications (1)

• Zeraik L, Rosi A, Del Rio D, Crozier A, Bresciani L, Mena P. Endogenous and/or exogenous origin of phenolic metabolites in humans (the ENDOPHENOL project): study protocol for a randomized, controlled, crossover trial. Trials. 2025 Dec 19;26(1):571. doi: 10.1186/s13063-025-09215-9.

  PMID: 41420184 DERIVED

MeSH Terms

Interventions

Coffee; Water

Intervention Hierarchy (Ancestors)

Plant Preparations; Biological Products; Complex Mixtures; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Pedro M Mena Parreño, PhD

  University of Parma

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pedro M Mena Parreño, PhD

CONTACT

+393288087332; pedromiguel.menaparreno@unipr.it

Letizia Bresciani, PhD

CONTACT

letizia.bresciani@unipr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SCREENING
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 23, 2023
• First Posted: September 8, 2023
• Study Start: October 25, 2023
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: April 8, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available from when published in peer-reviewed journals.
• Access Criteria: Data available in publications can be freely accessed. If further data is required to be shared, it will be assessed case by case.

Locations

IT (1)