Ignite Creation Date:
2025-12-25 @ 2:03 AM
Ignite Modification Date:
2025-12-27 @ 11:48 PM
Study NCT ID:
NCT05752760
Status:
RECRUITING
Last Update Posted:
2025-04-27
First Post:
2023-02-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pilot Study Lp299v Supplementation in Chronic Heart Failure
Sponsor:
Medical College of Wisconsin
Organization:
Study Overview
Official Title:
Impact of Lactobacillus Plantarum 299v Probiotic Supplementation on Vascular Function and Exercise Capacity in Chronic Heart Failure With Reduced and Preserved Ejection Fraction.
Status:
RECRUITING
Status Verified Date:
2025-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this study is to determine the impact of 12 weeks of Lp299v supplementation (20 million cfu/day vs. placebo) on exercise capacity, circulating biomarkers of cardiac remodeling, quality of life, and vascular endothelial function in humans with heart failure and reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) who have evidence of residual inflammation based on an elevated C-reactive protein level. This will be done in the setting of a randomized, double-blind, placebo-controlled trial.
Detailed Description:
Heart failure (HF) has significant morbidity and mortality and is one of the leading causes of hospital admissions in the United States. In 2017, almost 1 million people were affected and responsible for 1.2 million hospitalizations in the United States alone. Prognosis is poor for patients with HF despite significant medical therapy regimens and device therapy. Worldwide, mortality is as high as 17% during initial hospitalization, as high as 45% within one year of admission, and greater than 50% within five years. According to the Wisconsin Department of Health Services, mortality rates for HF have been increasing in the state since 1980. Wisconsin also consistently had higher rates of HF compared to the remaining states.
Emerging data suggest targeting the gut microbiota in HF could be a safe and effective alternative for mitigating inflammation. HF patients have increased systemic circulating endotoxins and lipopolysaccharides due to impaired gut-barrier function, secondary to gut congestion and reduced cardiac output, which drives systemic inflammation. The gut flora of patients with HF also includes more pathogenic bacteria species (candida, campylobacter, shigella, and yersinia) compared to patients with normal heart function.
Previous studies by the lab showed that supplementation of 20 billion cfu/day of Lactobacillus plantarum 299v (Lp299v) probiotic decreases systemic inflammation in men with stable coronary artery disease (CAD), and also improves vascular endothelial function (measured by endothelium-dependent vasodilation in the brachial artery and by nitric-oxide dependent vasodilation of resistance arterioles from CAD patients). The investigators have shown that there are significantly decreased levels of IL-8, IL-12 and Leptin in Lp299v-supplemented patients with CAD. Leptin is known to increase IL-6 (which drives increased C-reactive protein expression), IL-8, IL-12 and TNF-α levels, all which activate pro-inflammatory immune responses leading to vasoconstriction and vascular stiffness. Further, our data suggests Lp299v has a significant, favorable anti-inflammatory effect on signaling pathways (NLRP3, IL-6, IL-1β) shown to be important to chronic inflammation in heart failure.
Therefore, the investigators plan to perform a pilot study targeting the gut microbiota of patients with HF with oral supplementation with 20 billion cfu/day of Lp299 and determine if Lp299v improves peak oxygen consumption (measured by VO2 max testing), endothelial function (measured by brachial artery flow-mediated dilation), and vascular stiffness (measured by peak wave velocity). We plan to test the hypothesis that Lp299v will improve these measures in the setting of a randomized, double-blind, placebo-controlled clinical trial of 20 subjects. The investigators will additionally test if Lp299v supplementation improves circulating biomarkers of inflammation and cardiac remodeling in chronic heart failure, as well as if it improves the quality of life in patients using the Minnesota Living with Heart Failure Questionnaire and the Kansas City Cardiomyopathy Questionnaire.
Emerging data suggest targeting the gut microbiota in HF could be a safe and effective alternative for mitigating inflammation. HF patients have increased systemic circulating endotoxins and lipopolysaccharides due to impaired gut-barrier function, secondary to gut congestion and reduced cardiac output, which drives systemic inflammation. The gut flora of patients with HF also includes more pathogenic bacteria species (candida, campylobacter, shigella, and yersinia) compared to patients with normal heart function.
Previous studies by the lab showed that supplementation of 20 billion cfu/day of Lactobacillus plantarum 299v (Lp299v) probiotic decreases systemic inflammation in men with stable coronary artery disease (CAD), and also improves vascular endothelial function (measured by endothelium-dependent vasodilation in the brachial artery and by nitric-oxide dependent vasodilation of resistance arterioles from CAD patients). The investigators have shown that there are significantly decreased levels of IL-8, IL-12 and Leptin in Lp299v-supplemented patients with CAD. Leptin is known to increase IL-6 (which drives increased C-reactive protein expression), IL-8, IL-12 and TNF-α levels, all which activate pro-inflammatory immune responses leading to vasoconstriction and vascular stiffness. Further, our data suggests Lp299v has a significant, favorable anti-inflammatory effect on signaling pathways (NLRP3, IL-6, IL-1β) shown to be important to chronic inflammation in heart failure.
Therefore, the investigators plan to perform a pilot study targeting the gut microbiota of patients with HF with oral supplementation with 20 billion cfu/day of Lp299 and determine if Lp299v improves peak oxygen consumption (measured by VO2 max testing), endothelial function (measured by brachial artery flow-mediated dilation), and vascular stiffness (measured by peak wave velocity). We plan to test the hypothesis that Lp299v will improve these measures in the setting of a randomized, double-blind, placebo-controlled clinical trial of 20 subjects. The investigators will additionally test if Lp299v supplementation improves circulating biomarkers of inflammation and cardiac remodeling in chronic heart failure, as well as if it improves the quality of life in patients using the Minnesota Living with Heart Failure Questionnaire and the Kansas City Cardiomyopathy Questionnaire.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: