Effect of Probiotic Supplementation on Endothelial Function II

RECRUITING

I'm interested ...!!

Researchers at MCW have discovered a new pathway that links the type of bacteria present in the intestines to the severity of heart attacks. This discovery of a relationship between intestinal bacteria, bacterial metabolites, and severity of heart attacks means that for the first time, the investigators may be able to determine a person's probability of having a heart attack via non-conventional risk factors. This may provide opportunities for novel diagnostic tests as well as a potential for therapeutic intervention. The link between gut microbiota and the severity of heart attacks may also lead to novel therapeutic approaches (probiotics, non-absorbable antibiotics) to prevent heart attacks from happening. The studies proposed will test the hypothesis that altered intestinal microbiota are mechanistically linked to the pathogenesis of cardiovascular disease. The investigator's objective is to determine whether inflammatory markers in the blood are decreased and endothelial cell function improved by a probiotic in patients with established coronary artery disease. Furthermore, the investigators wish to elucidate a mechanism by which the gut microbiota regulates serum inflammatory markers. 1. Specific Aim 1 will determine the impact of a probiotic on circulating leptin and TMAO levels, conventional risk factors for cardiovascular disease and diabetes (total cholesterol, LDL cholesterol, oxidized LDL, triglycerides, C-reactive protein, serum amyloid A, fibrinogen and adiponectin, glucose-dependent- insulinotropic polypeptide (GIP), glucagon-like-peptide (GLP-1), glucagon, insulin), and their relationship to the intestinal microbiota (15 representative microbial groups) as non conventional risk factors. Several blood samples will be collected to measure biomarkers. Participants will provide periodic stool samples in order to measure gut bacterial biodiversity. Lastly, endothelial cell function (flow mediated dilation) will be measured in order to assess blood vessel function. 2. Specific Aim 2 will determine the impact of a probiotic on metabolites derived from the intestinal microbiota as candidates for non-conventional risk factors of cardiovascular disease. The relationship between metabolites derived from the intestinal microbiota, endothelial cell function and risk factors for cardiovascular disease identified in Specific Aim 1 will be correlated.

Conditions:

🦠 Cardiovascular Disease 🦠 Diabetes Mellitus, Type 2

🗓️ Study Start (Actual) 15 May 2018

🗓️ Primary Completion (Estimated) 5 September 2025

✅ Study Completion (Estimated) 30 November 2025

👥 Enrollment (Estimated) 215

🔬 Study Type INTERVENTIONAL

📊 Phase NA

Locations:

📍 Milwaukee, Wisconsin, United States

📋 Eligibility Criteria

Description

CAD Inclusion Criteria
Age between 40-80 years old History of known coronary artery disease (by either history of myocardial infarction, angiogram demonstrative \>=50% stenosis in at least 1 major epicardial coronary artery, or a previous stress test that showed evidence of ischemia that has not been revealed to be a false positive test by angiography)
T2DM without CAD Inclusion Criteria
1. Age between 40-80 years old
2. History of known Diabetes Mellitus Type II as previously diagnosed by patient's provider (ICD-9/10 code)
CAD Exclusion Criteria
Unstable angina or myocardial infarction by history, ECG, and/or enzymatic criteria within 1 month of enrollment.
LV dysfunction as defined by an LV ejection fraction documented as \< 45% within 1 year of enrollment by an echocardiogram, MRI, or nuclear imaging.
Uncontrolled hypertension with a blood pressure greater than 170/100 mmHg at the screening visit.
Known history of chronic renal insufficiency, liver dysfunction, or cancer besides non-melanoma skin carcinomas or localized prostate cancer requiring systemic treatment within five years of enrollment.
Known history of cognitive impairment or inability to follow study procedures Patient with GI tract illness such as short gut syndrome, inflammatory bowel disease, or an ileostomy.
Patient with an implanted defibrillator or permanent pacemaker on which the potential participant is known to rely upon for greater than 50% of ventricular depolarizations.
Patients who received probiotics, prebiotics, and antibiotics in the last 12 weeks.
Patients with dosing changes of vasoactive medications and HMG-CoA reductase inhibitors in the 6 weeks prior to enrollment.
Pregnancy Patients who is currently taking Vitamin K anatagonists such as coumadin, warfarin.
Those who are daily drinkers or use illicit drugs.
T2DM without CAD Exclusion Criteria
Hgb A1C \> 9.5 % Coronary Artery Disease (by either history of myocardial infarction, angiogram demonstrative \>=50% stenosis in at least 1 major epicardial coronary artery, or a previous stress test that showed evidence of ischemia that has not been revealed to be a false positive test by angiography) Unstable angina or myocardial infarction by history, ECG, and/or enzymatic criteria within 1 month of enrollment.
LV dysfunction as defined by an LV ejection fraction documented as \< 45% within 1 year of enrollment by an echocardiogram, MRI, or nuclear imaging.
Uncontrolled hypertension with a blood pressure greater than 170/100 mmHg at the screening visit.
Known history of chronic renal insufficiency, liver dysfunction, or cancer besides non-melanoma skin carcinomas or localized prostate cancer requiring systemic treatment within five years of enrollment.
Known history of cognitive impairment or inability to follow study procedures Patient with GI tract illness such as short gut syndrome, inflammatory bowel disease, or an ileostomy.
Patient with an implanted defibrillator or permanent pacemaker on which the potential participant is known to rely upon for greater than 50% of ventricular depolarizations.
Patients who received probiotics, prebiotics, and antibiotics in the last 12 weeks.
Patients with dosing changes of vasoactive medications and HMG-CoA reductase inhibitors in the 6 weeks prior to enrollment.
Pregnancy Patients who is currently taking Vitamin K anatagonists such as coumadin, warfarin.
Those who are daily drinkers or use illicit drugs.

Ages Eligible for Study: 40 Years to 80 Years (ADULT, OLDER_ADULT)

Sexes Eligible for Study: ALL

Accepts Healthy Volunteers: No

🗓️ 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 Registration Dates

First Submitted 10 August 2017
First Submitted that Met QC Criteria 29 August 2017
First Posted 30 August 2017

Study Record Updates