Clinical trial NCT03232099: Red Wine Effects Upon Gut Flora and Plasma Levels of Trimethylamine-N-oxide (TMAO) - WineFlora Study
Official title: Evaluation of Red Wine Effects Upon Gut Flora and Plasma Levels of Trimethylamine-N-oxide (TMAO) in Patients With Established Atherosclerotic Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Trimethylamine-N-oxide
Gut Microbiota
Effects of Red Wine
Atherosclerosis
Keywords: trimethylamine-N-oxide
TMAO
Gut Microbiota
Gut Flora
Atherosclerosis
Wine
Red Wine
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
name: IBRAVIN
First posted: 2017-07-27
Enrollment: 42
Sex: MALE
Minimum age (years): 45
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Forty two men with established atherosclerotic disease will be studied:after a 2 week washout period, each subject receives both treatments, intervention and control
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: up to 10 weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Instituto do Coração - InCor - University of Sao Paulo General Hospital
name: Protasio L da Luz, Professor
role: STUDY_CHAIR
affiliation: Instituto do Coração - InCor - University of Sao Paulo General Hospital
name: Elisa A Haas, MD
role: PRINCIPAL_INVESTIGATOR
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