Effect of Probiotic Supplementation on Endothelial Function II

NCT03267758 | Completed

• 1 other identifier: PRO27955
• Study Type: interventional
• Target: 215
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 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

Outcome Measures

Primary Outcomes (1)

• change in baseline flow mediated dilation (FMD) at 6 weeks

  This is a measurement of endothelial function in the brachial artery

  baseline and week 6

Study Arms (2)

Goodbelly First

EXPERIMENTAL

Subjects in this arm will consume 1 serving of lactobacillus plantarum 299v daily for first 6 weeks.

Dietary Supplement: Goodbelly first

Placebo

PLACEBO COMPARATOR

Subjects in this arm will consume 1 serving of heat-killed placebo daily for first 6 weeks.

Dietary Supplement: Placebo first

Interventions

Goodbelly first DIETARY_SUPPLEMENT

Consumption of 1 serving of Goodbelly probiotic daily for 6 weeks. This is followed by 6 weeks of placebo.

Also known as: Goodbelly

Goodbelly First

Placebo first DIETARY_SUPPLEMENT

Consumption of 1 serving of probiotic placebo daily for 6 weeks. of 1 serving of Goodbelly probiotic daily for 6 weeks.

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Age between 40-80 years old
• History of known Diabetes Mellitus Type II as previously diagnosed by patient's provider (ICD-9/10 code)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (9)

• Lam V, Su J, Koprowski S, Hsu A, Tweddell JS, Rafiee P, Gross GJ, Salzman NH, Baker JE. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J. 2012 Apr;26(4):1727-35. doi: 10.1096/fj.11-197921. Epub 2012 Jan 12.

  PMID: 22247331 BACKGROUND

• Naruszewicz M, Johansson ML, Zapolska-Downar D, Bukowska H. Effect of Lactobacillus plantarum 299v on cardiovascular disease risk factors in smokers. Am J Clin Nutr. 2002 Dec;76(6):1249-55. doi: 10.1093/ajcn/76.6.1249.

  PMID: 12450890 BACKGROUND

• Widlansky ME, Gokce N, Keaney JF Jr, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003 Oct 1;42(7):1149-60. doi: 10.1016/s0735-1097(03)00994-x.

  PMID: 14522472 BACKGROUND

• Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R; International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002 Jan 16;39(2):257-65. doi: 10.1016/s0735-1097(01)01746-6.

  PMID: 11788217 BACKGROUND

• Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992 Nov 7;340(8828):1111-5. doi: 10.1016/0140-6736(92)93147-f.

  PMID: 1359209 BACKGROUND

• Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, Widlansky ME, Tschakovsky ME, Green DJ. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011 Jan;300(1):H2-12. doi: 10.1152/ajpheart.00471.2010. Epub 2010 Oct 15.

  PMID: 20952670 BACKGROUND

• Takase B, Uehata A, Akima T, Nagai T, Nishioka T, Hamabe A, Satomura K, Ohsuzu F, Kurita A. Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease. Am J Cardiol. 1998 Dec 15;82(12):1535-9, A7-8. doi: 10.1016/s0002-9149(98)00702-4.

  PMID: 9874063 BACKGROUND

• Vita JA, Keaney JF Jr. Endothelial function: a barometer for cardiovascular risk? Circulation. 2002 Aug 6;106(6):640-2. doi: 10.1161/01.cir.0000028581.07992.56. No abstract available.

  PMID: 12163419 BACKGROUND

• Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013 Apr 25;368(17):1575-84. doi: 10.1056/NEJMoa1109400.

  PMID: 23614584 RESULT

MeSH Terms

Conditions

Cardiovascular Diseases; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Michael Widlansky, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: August 10, 2017
• First Posted: August 30, 2017
• Study Start: May 15, 2018
• Primary Completion: October 16, 2025
• Study Completion: October 16, 2025
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

US (1)