Intestinal Microbiome and Extremes of Atherosclerosis

Patients attending stroke prevention clinics and a premature atherosclerosis clinic at University Hospital in London, ON, Canada were recruited to the study. They completed a dietary questionnaire, provided stool samples and had blood drawn to measure plasma levels of metabolites produced by the intestinal bacteria.

Study Overview

• Status: Completed
• Conditions: Renal Function; Gastrointestinal Microbiome, Atherosclerosis, Nutrients
• Intervention / Treatment: Diagnostic test: Plasma levels of metabolites; Behavioral: Dietary questionnaire; Diagnostic test: Intestinal microbiome

Detailed Description

Patients were phenotyped by their residual score in linear multiple regression with measured carotid plaque burden as the dependent variable and coronary risk factors were predictors. The residual score essentially represents the distance off the regression line of predicted plaque. They were grouped into three categories: Unexplained atherosclerosis (with more plaque than predicted by risk factors; residual score >2); Explained (the amount of plaque predicted by risk factors, residual score >-2 and <2); and Protected (less plaque than predicted by risk factors, residual score <-2).

DNA was extracted from stool samples in the lab of Dr. Allen-Vercoe at University of Guelph. RNA makeup of the intestinal microbiome was assessed in the lab of Dr. Gregory Gloor at Western. Plasma levels of trimethylamine n-oxide, p-cresylsulfate, hippuric acid, p-cresyl glucuronide, pheny acetyl glutamine and phenyl sulfate were measured by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry in the lab of Dr. Bradley Urquhart at Western.

Nutrient intake over the past year was calculated at the Harvard School of Public Health from the 131 item self-reported and semi-quantitative Harvard Food Frequency Questionnaire (FFQ).

Estimated glomerular filtration rate was calculated from the Chronic Kidney Disease Epidemiological (CKD-EPI) equations.

• Study Type: Observational
• Enrollment (Actual): 316

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6G 2V4
      • Stroke Prevention & Atherosclerosis Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

as above

Description

Inclusion Criteria:

• Patients attending stroke prevention clinics and a Premature Atherosclerosis Clinic at University Hospital, London, ON, Canada,
• with measurements of carotid plaque burden and the risk factors used in the linear regression model.
• Willing to consent to the protocol approved by the Ethics board

Exclusion Criteria:

• Missing data on variables used in the regression model,

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Unexplained Atherosclerosis phenotype; Residual score in linear regression >2	Diagnostic test: Plasma levels of metabolites; plasma levels of metabolites; Behavioral: Dietary questionnaire; Harvard food frequency questionnaire; Diagnostic test: Intestinal microbiome; amplification and sequencing of 16S rRNA gene variable regions in stool samples
Explained Atherosclerosis phenotype; Residual score in linear regression <-2, <2	Diagnostic test: Plasma levels of metabolites; plasma levels of metabolites; Behavioral: Dietary questionnaire; Harvard food frequency questionnaire; Diagnostic test: Intestinal microbiome; amplification and sequencing of 16S rRNA gene variable regions in stool samples
Protected Atherosclerosis phenotype; Residual score <-2	Diagnostic test: Plasma levels of metabolites; plasma levels of metabolites; Behavioral: Dietary questionnaire; Harvard food frequency questionnaire; Diagnostic test: Intestinal microbiome; amplification and sequencing of 16S rRNA gene variable regions in stool samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of metabolites in the three phenotypes	Plasma levels of trimethylamine n-oxide, p-cresylsulfate, hippuric acid, p-cresyl glucuronide, pheny acetyl glutamine and phenyl sulfate	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacterial profile of the intestinal microbiome	Amplification and sequencing of 16S rRNA gene variable regions	Day 1
Effect of nutrient intake on plasma levels of metabolites	Nutrient analysis from food frequency questionnaire	Day 1
Effect of renal function on plasma levels of metabolites	eGFR from CKD-EPI equations	Day 1

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): October 15, 2016
• Study Completion (Actual): October 15, 2016

Study Registration Dates

• First Submitted: December 12, 2017
• First Submitted That Met QC Criteria: January 11, 2018
• First Posted (Actual): January 16, 2018

Study Record Updates

• Last Update Posted (Actual): January 16, 2018
• Last Update Submitted That Met QC Criteria: January 11, 2018
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: atherosclerosis; renal function; intestinal microbiome; nutrients
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis
• Other Study ID Numbers: 105166

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: It will depend on requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No