Clinical trial NCT01952834: Effect of Probiotic Supplementation on Endothelial Function
Official title: Effect of Probiotic Supplementation on Endothelial Function in Men With Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: coronary artery disease
probiotic
endothelial function
brachial artery
ntric oxide
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
First posted: 2013-09-30
Enrollment: 21
Sex: MALE
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study is being performed to determine whether probiotics (GoodBelly) improves blood vessel function.Probiotics similar to yogurt are living micro-organisms (beneficial to its host) the lives in the intestine. Patients who have coronary artery disease will be enrolled in this study. The research results will be used to determine if the type of bacteria present in the intestines play a role in the pathogenesis of cardiovascular disease. Patients with coronary artery disease will be enrolled for up to 12 weeks. Patients will take the probiotic for 6 weeks. Following the 6 week period there is a washout period of 4 weeks, and an optional antibiotic study called vancomycin. Patients will take the vancomycin for 10 days. Blood vessel function will be measured by ultrasound before and after the probiotic supplement and vancomycin antibiotic. Blood will also be taken before and after to evaluate for markers of inflammation.

Detailed description: We plan to recruit 20 patients, men with coronary artery disease, for this single center, interventional trial with the Probiotic-GoodBelly followed by Vancomycin. The study includes 6 total visits. Subjects who pass a phone screen will be invited to a screening visit for study eligibility (Visit 1) Informed consent will be reviewed; a unique study number will be assigned once written informed consent is obtained (no subject will be assigned more than 1 allocation number); relevant participant medical history will be recorded including currently prescribed medications; anthropometric measurements will be taken (height, weight, and waist circumference in metric units) and blood pressure will be recorded (measured in triplicate and averaged). Subjects will be allowed to take their blood pressure medication on the morning of their screening visit, but not the mornings of any of the other study visits to limit the acute influence of these medications on endothelial function. If the potential participant qualifies for the study, he will return 1 week after the screen for a study visit(Visit 2) where he will turn in his stool sample, undergo initial tests of endothelial function and receive 3 week supply of GoodBelly Probiotic. After 3 weeks he will have to return (Visit 3) for another 3 week supply of his probiotic. After a total of 6 weeks of taking the probiotic he will have to return (Visit 4) with his stool sample. He will be asked to fast for 6-8 hours prior to the visit to limit the acute dietary influences on vascular endothelial function. During Visit 4, endothelial function will determined by brachial artery reactivity testing His stool samples will be collected and blood samples will also be taken at this visit for systemic measurements inflammatory markers. If he agrees to the optional Vancomycin study. He will return after 4 weeks for (Visit 5). He will be asked to fast for 6-8 hours prior to the visit to limit the acute dietary influences on vascular endothelial function. At Visit 5, endothelial function will determined by brachial artery reactivity testing His stool samples will be collected and blood samples will also be taken at this visit for systemic measurements inflammatory markers. He will then be given a 10 day supply of vancomycin. After 10 days he will return (Visit 6) with his stool sample. At Visit 6, endothelial function will determined by brachial artery reactivity testing . His stool samples will be collected and blood samples will also be taken at this visit for systemic measurements inflammatory markers.

Eligibility criteria: Inclusion Criteria:

1. Age between 40-75 years old
2. Male sex
3. 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)

Exclusion Criteria:

1. Unstable angina or myocardial infarction by history, ECG, and/or enzymatic criteria within 1 month of enrollment.
2. Left ventricular dysfunction as defined by an left ventricular ejection fraction documented as \< 45% within 1 year of enrollment by an echocardiogram, MRI, or nuclear imaging.
3. Uncontrolled hypertension with a blood pressure greater than 170/100 mmHg at the screening visit.
4. 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.
5. Known history of cognitive impairment or inability to follow study procedures
6. Patient with an implanted defibrillator or permanent pacemaker on with the potential participant is known to rely upon for greater than 50% of ventricular depolarizations.
7. Patients who received probiotics, prebiotics, and antibiotics in the last 12 weeks.
8. Patients with dosing changes of vasoactive medications and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in the 6 weeks prior to enrollment.

Primary outcomes:
measure: Brachial Artery Flow Mediated Dilation
timeFrame: % Change before and after 6 weeks of daily Probiotic
measure: Brachial Artery Flow Mediated Dilation
timeFrame: Change before and after 10 days of Vancomycin, approximately 12 weeks from baseline
Secondary outcomes:
measure: Interleukin 8
timeFrame: Change before and after 6 weeks of daily Probiotic
measure: Interleukin-12
timeFrame: Change before and after 6 weeks of probiotic
Other outcomes:
Locations:
city: Milwauke
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Michael E Widlansky, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: John Baker, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Malik M, Suboc TM, Tyagi S, Salzman N, Wang J, Ying R, Tanner MJ, Kakarla M, Baker JE, Widlansky ME. Lactobacillus plantarum 299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men With Stable Coronary Artery Disease. Circ Res. 2018 Oct 12;123(9):1091-1102. doi: 10.1161/CIRCRESAHA.118.313565.