Red Wine Effects Upon Gut Flora and Plasma Levels of Trimethylamine-N-oxide (TMAO) - WineFlora Study

March 10, 2021 updated by: University of Sao Paulo General Hospital

Evaluation of Red Wine Effects Upon Gut Flora and Plasma Levels of Trimethylamine-N-oxide (TMAO) in Patients With Established Atherosclerotic Disease

Recent evidence indicates that Trimethylamine-N-oxide (TMAO) is a pro-atherosclerotic, phosphatidylcholine-dependent metabolite of diet and intestinal flora. Food substrates derive from carnitine and phosphatidylcholine (lecithin), present mainly in eggs, red meat, liver and pork. The intestinal flora pattern that favors the formation of TMAO is very similar to that which predisposes to insulin resistance and obesity: a high proportion between phylum Firmicutes over Bacteroidetes. The intestinal microbiota is sensitive and variable; the use of prebiotics and probiotics can change the relationship between Firmicutes/Bacteroidetes phyla. Red wine (RW), for its composition with polyphenols and possible bactericidal role, may play a role in the intestinal flora modification and could promote proliferation of beneficial bacteria. However, the influence of RW on TMAO is not known. This is the hypothesis to be tested in this trial. METHODS: This is a prospective, crossover, randomized, controlled trial with patients from Heart Institute (InCor), FMUSP and volunteers recruited through press releases. We will evaluate 42 patients, all men, with established atherosclerotic disease. Patients will be evaluated in a crossed manner: each subject receives both treatments, intervention and control (in random order), and they will be divided into 2 groups: A and B. In the first intervention stage, after 2 weeks of washout for all patients , group A receives Red Wine (RW) and group B is the control, abstemious. In the 2nd stage of intervention, after 2 weeks of washout for all patients the groups are inverted: group B receives RW; and group A will be abstemious. In the period with wine intervention, patients will receive 250 mL/day of red wine per day, for 5 days of the week, for 3 weeks. Patients will maintain their usual diet without the use of prebiotics or probiotics, or other polyphenolic derivatives. At the beginning and at the end of each stage, patients will be submitted to serum TMAO and intestinal microbiota evaluation. For the intestinal microbiota evaluation, the new generation sequencing will be used in the highly preserved portion of the 16S subunit of the rRNA gene. The determination of TMAO in plasma will be by liquid chromatography coupled to mass spectrometry. Expected results: It is expected to determine if RW acts on the intestinal flora to the point of influencing plasma TMAO concentration.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  1. Men, 45-70 years
  2. Established atherosclerotic diseases defined as:

A. Previous history of CAD: angina or acute myocardial infarction (AMI), myocardial revascularization or angioplasty, angiographic evidence of stenosis ≥50% in at least one of the major coronary arteries B. Cerebrovascular disease: transient ischemic stroke or cerebrovascular accident C. Peripheral arterial disease: clinical evidence of extracoronary atherosclerosis

Exclusion Criteria:

  1. Acute events in the last 30 days (AMI, troponin elevation, coronary angioplasty or coronary artery bypass grafting)
  2. Heart Failure (NYHA functional class ≥ II)
  3. Renal Failure (clearance creatinine <30 mL / min by the Cockcroft-Gault formula)
  4. Hepatic Failure
  5. Gastro-intestinal cancer
  6. Intestinal inflammatory diseases
  7. Obstructive biliary diseases
  8. Prior gastrointestinal surgeries: cholecystectomy or colectomy
  9. Use of antibiotics within the last 2 months or during protocol
  10. Alcoholism or alcohol intolerance
  11. Diabetes mellitus or use of antidiabetics drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Red Wine group (RW)
After a two weeks washout period,in the intervening period with red wine, patients will receive 250 mL / day of red wine per Day, 5 days a week, for 3 weeks.
Dietary supplement: Red Wine consumption
After a two weeks washout period,in the intervening period with red wine, patients will receive 250 mL / day of red wine per Day, 5 days a week, for 3 weeks.
Active Comparator: Abstemious
After a two weeks washout period,in the Abstemious period, patients should not consume any kind of alcohol beverages, for 3 weeks
Other: Period without alcohol consumption
After a two weeks washout period,in the Abstemious period, patients should not consume any kind of alcohol beverages, for 3 weeks
Other Names:
  • Abstain Period

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gut flora modification assessed by 16S ribosomal rNA gene sequencing and plasma concentration of TMAO changes measured by liquid chromatography coupled to mass spectrometry in 42 patients after ingestion 250 mL of Red Wine 5 days/week, for 3 weeks
Time Frame: up to 10 weeks
Patients will be divided into 2 groups: A and B. In the first intervention stage, after 2 weeks of washout for all patients , group A receives Red Wine (RW) and group B is the control, abstemious. In the 2nd stage of intervention, after 2 weeks of washout for all patients the groups are inverted: group B receives RW; and group A will be abstemious. In the period with wine intervention, patients will receive 250 mL/day of red wine per day, for 5 days of the week, for 3 weeks. Patients will maintain their usual diet without the use of prebiotics or probiotics, or other polyphenolic derivatives. At the beginning and at the end of each stage, patients will be submitted to serum TMAO and intestinal microbiota evaluation. For the intestinal microbiota evaluation, the new generation sequencing will be used in the highly preserved portion of the 16S subunit of the rRNA gene. The determination of TMAO in plasma will be by liquid chromatography coupled to mass spectrometry
up to 10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo General Hospital

Collaborators

Fundação de Amparo à Pesquisa do Estado de São Paulo
IBRAVIN

Investigators

  • Study Chair: Protasio L da Luz, Professor, Instituto do Coração - InCor - University of Sao Paulo General Hospital
  • Principal Investigator: Elisa A Haas, MD, Instituto do Coração - InCor - University of Sao Paulo General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 31, 2016

Primary Completion (Actual)

March 22, 2018

Study Completion (Actual)

April 15, 2018

Study Registration Dates

First Submitted

June 20, 2017

First Submitted That Met QC Criteria

July 26, 2017

First Posted (Actual)

July 27, 2017

Study Record Updates

Last Update Posted (Actual)

March 15, 2021

Last Update Submitted That Met QC Criteria

March 10, 2021

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 57379216.0.0000.0068
  • 2015/212606 (Other Grant/Funding Number: FAPESP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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