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Metabotypes in the Urinary Excretion of Flavan-3-ol Metabolites: "Metanols" (Metanols)

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ClinicalTrials.gov Identifier: NCT04124016
Recruitment Status : Recruiting
First Posted : October 11, 2019
Last Update Posted : October 11, 2019
Sponsor:
Collaborator:
Azienda Ospedaliero-Universitaria di Parma
Information provided by (Responsible Party):
Professor Furio Brighenti, University of Parma

Brief Summary:

Flavan-3-ols are the main source of flavonoids in Western diets. They are characteristic compounds of tea, cocoa, wine, apple, pears, etc. In plant-based foods, they occur as simple monomers or as oligomers and polymers of up to 50 units (also known as proanthocyanidins or condensed tannins). When ingested, both monomeric and high molecular weight flavan-3-ols are poorly absorbed and metabolized in the first gastrointestinal tract, reaching the colon and becoming a suitable substrate for the local microbiota. These compounds undergo an extensive microbial metabolism leading to the formation of hydroxyphenyl-γ- valerolactones (PVLs), which are then absorbed by colonocytes before reaching the liver and being converted into phase II conjugated metabolites. Since the microbiota composition varies among individuals, it results in differences in the production of PVLs and, consequently, the health effects of flavan-3-ols might change at an individual level.

Another factor of variability might be due to a different asset in the fermentation of indigestible dietary carbohydrates, which are known to modify colonic pH through the production of short-chain fatty acids and may result in different profiles of gas production (i.e. hydrogen and methane), possibly affecting the bioconversion of flavan-3-ols as well. Nevertheless, these multiple variabilities are poorly understood to date.


Condition or disease Intervention/treatment Phase
Diet Modification Dietary Supplement: Inulin Dietary Supplement: green tea extract Dietary Supplement: grape seed Dietary Supplement: grape seed extract Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: single-dose, partially randomized, cross over design with 4 consecutive treatments
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Metabotypes in the Urinary Excretion of Flavan-3-ol Metabolites
Actual Study Start Date : September 2, 2019
Estimated Primary Completion Date : January 24, 2020
Estimated Study Completion Date : March 27, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Inulin
Inulin_ extract of chicory fermentable fiber
Dietary Supplement: Inulin
Powder of inulin fractions dissolved into 250 ml of water

Experimental: green tea extract
green tea extract_rich in tri-hydroxylated flavan-3-ol monomers (1 mmol of PVL precursor)
Dietary Supplement: green tea extract
Powder of green tea extract dissolved into 200 ml of water

Experimental: grape seed
grape seed extract - rich in di-hydroxylated flavan-3-ol monomers (1 mmol of PVL precursors)
Dietary Supplement: grape seed
Powder of grape seed extract (rich in di-hydroxylated flavan-3-ol monomers) dissolved into 200 ml of water

Experimental: grape seed exctract
grape seed extract - rich in di-hydroxylated flavan-3-ol oligomers (1 mmol of PVL precursors)
Dietary Supplement: grape seed extract
Powder of grape seed extract (rich in di-hydroxylated flavan-3-ol oligomers) dissolved into 200 ml of water




Primary Outcome Measures :
  1. Assessing the formation of urinary metabotypes of flavan-3-ol colonic metabolites [ Time Frame: AUC for 24 hours (sum of 0-180; 180-360; 360-540; 540-720; 720-1440 minutes) ]
    Assessing the variability of the area under the curve of the urinary concentration of some phenolic metabolites ( tri- and di-hydroxyphenyl-γ-valerolactones and 3-hydroxyphenylpropionic acids (umol)) after consumption of 3 different sources of flavan-3-ols by using data-driven clustering.


Secondary Outcome Measures :
  1. Evolution over the time of the metabolites of flavan-3-ols in urine samples [ Time Frame: AUC for 48 hours (sum of 0-180; 180-360; 360-540; 540-720; 720-1440; 1440-2160; 2160-2880; 2880 minutes) ]
    Assessed by using UHPLC-MSn for individual detection and quantification.

  2. Identification of Firmicutes, bacteroidetes and Archea in faecal samples of participants [ Time Frame: Baseline ]
    Firmicutes, Bacteroidetes and Archea main species assessed by an optimized 16S rRNA gene-based analysis protocol.

  3. Evaluation of inter-individual differences on breath-gases production (hydrogen and methane) on alveolar air samples [ Time Frame: AUC for 12 hours; (sum of 60; 120; 180; 240; 300; 360; 420; 480; 540; 600; 660; 720 minutes) ]
    Performed by using a hydrogen/methane analyser

  4. Correlations between colonic fermentation, gas production and microbiota composition and metabotypes [ Time Frame: 24 hours ]
    multiple correlation between in vitro short chain fatty acids and gas production, microbiota composition and metabotype through PCA and PLS-DA.

  5. In vitro variation of gases production by fermentable dietary fibre in presence of polyphenols using faecal starters [ Time Frame: Baseline ]
    Gasses production will be assessed using a hydrogen/methane analyser

  6. In vitro variation of short chain fatty acids production of fermentable dietary fibre in presence of polyphenols using faecal starters [ Time Frame: Baseline ]
    Short chains fatty acids will be quantified using GC-MS

  7. Untargeted metabolomics on urine samples [ Time Frame: 24 hours ]
    Metabolomics will be carried out in urine using HR-LC-MS/MS to unravel the potential metabolic pathways of molecules present after the consumption of the different sources of flavan-3-ols.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adult
  • Both genders
  • Healthy
  • BMI > 18.5
  • BMI < 30

Exclusion Criteria:

  • Metabolic disorder or surgeries of liver, kidney or gastrointestinal tract
  • Immunodeficiency
  • Food intolerance or allergies
  • Regular consumption of medication
  • Antibiotic therapy within the last 3 months
  • Use of food supplements, including pro- and prebiotics
  • Intense physical activity (PAL ≥ 2.10)
  • Pregnancy
  • Lactation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04124016


Contacts
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Contact: Furio FB Brighenti, Professor +39 0521 903835 furio.brighenti@unipr.it

Locations
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Italy
University of Parma Recruiting
Parma, Italy, 43125
Contact: Pedro Mena, PhD    0521 903841    pedromiguel.menaparreno@unipr.it   
Contact: Rossella Dodi, Msc    0521 903841    rosselladodi.90@gmail.com   
Principal Investigator: Furio Brighenti, Professor         
Sponsors and Collaborators
University of Parma
Azienda Ospedaliero-Universitaria di Parma
Investigators
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Principal Investigator: Furio FB Brighenti, Professor University of Parma
Study Director: Daniele DR Del Rio, Professor University of Parma
Study Director: Pedro Miguel PM Mena Parreño, Ph.D. University of Parma
Study Director: Rossella RD Dodi, M. Sc. University of Parma

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Responsible Party: Professor Furio Brighenti, Professor, University of Parma
ClinicalTrials.gov Identifier: NCT04124016     History of Changes
Other Study ID Numbers: 796/2018/SPER/UNIPR
First Posted: October 11, 2019    Key Record Dates
Last Update Posted: October 11, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Professor Furio Brighenti, University of Parma:
flavan-3-ol
phenyl-y-valerolactones
catechins
metabotype
gas production
gut microbiota
Additional relevant MeSH terms:
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Grape Seed Extract
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs