Pilot Study Lp299v Supplementation in Chronic Heart Failure

April 27, 2026 updated by: Michael E. Widlansky, Medical College of Wisconsin

Impact of Lactobacillus Plantarum 299v Probiotic Supplementation on Vascular Function and Exercise Capacity in Chronic Heart Failure With Reduced and Preserved Ejection Fraction.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age between 21-89 years old
  • Clinical diagnosis of Congestive Heart Failure (CHF) in the six months prior to enrollment along with an echocardiogram documenting systolic dysfunction with ejection fraction ≤40%
  • Clinical diagnosis of CHF in the six months prior to enrollment along with an echocardiogram documenting diastolic dysfunction with an ejection fraction ≥50%, and a H2FpEFF score of ≥6
  • New York Heart Association (NYHA) Class II-IIID heart failure symptoms with either ischemic or non-ischemic etiology OR similar diagnosis with congestive heart failure (CHF) along with an echocardiogram documenting an LV ejection fraction of 50% or more with similar NYHA classification as those with LVEF of 40% or less
  • Evidence of systemic inflammation at baseline (C-reactive protein ≥ 2 mg/L at the time of screening)

Exclusion Criteria:

  • Heart failure due to severe valve disease such as Aortic Stenosis, Mitral Regurgitation, or Mitral Stenosis
  • Cancer besides non-melanoma skin carcinomas or localized prostate and breast cancer at the time of enrollment with life expectancy <1 year
  • Lung disease such as Chronic Obstructive Pulmonary Disease (COPD), emphysema, or Pulmonary fibrosis
  • Active inflammatory disease or infectious disease at the time of enrollment
  • Current treatment (or use within the past 14 days) of steroids or anti-inflammatory treatments (excluding non-steroidal anti-inflammatory medications or steroids used solely for IV contrast dye allergy)
  • Chronic Kidney Disease with eGFR ≤ 30 mL/min
  • Hepatic Failure (Child's Class B or C)
  • Patients with Gastrointestinal (GI) tract illness such as short gut syndrome, inflammatory bowel disease, or an ileostomy, such that probiotic absorption would be altered
  • Anticipated need for cardiac surgery during the projected study period for the subject
  • Pregnancy
  • Patients who are receiving Vitamin K antagonists such as Coumadin or Warfarin
  • Neutropenia (Absolute Neutrophil Count (ANC) < 1800/mm3)
  • Inability to give informed consent or follow the study protocol
  • On antibiotics at the time of enrollment or within one month of enrollment
  • Currently taking a Lactobacillus based probiotic as an outpatient at the time of enrollment
  • Patients who are unable to walk on treadmill or use a bicycle to participate in exercise testing
  • Allergy to Lp299v probiotic supplement

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lp299v
Subjects will consume 20 billion colony forming units of Lp299v (2 capsules) once daily for 12 weeks.
Other: Lactobacillus Plantarum 299v Freeze Dried Capsule
The intervention is a probiotic lactobacillus that is contained in food products in the US
Placebo Comparator: Placebo Control
Subjects will consume potato starch (2 capsules) once daily for 12 weeks.
Other: Freeze Dried Potato Starch Capsule
The intervention is potato starch that is freeze dried designed to mimic the lp299v capsule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximal Oxygen Consumption (VO2Max)
Time Frame: 12 weeks
This is a measurement of exercise capacity
12 weeks
Brachial Artery Flow Mediated Dilation (FMD%)
Time Frame: 12 weeks
This is a measurement of endothelial function in the brachial artery
12 weeks
Carotid-Femoral Pulse Wave Velocity (cfPWV)
Time Frame: 12 weeks
Measurement of vascular stiffness
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brachial Artery Absolute Flow Mediated Dilation (FMDmm)
Time Frame: 12 weeks
This is a measurement of endothelial function in the brachial artery
12 weeks
Resting shear stress of brachial artery
Time Frame: 12 weeks
This is a measurement of vascular stiffness
12 weeks
Resting velocity
Time Frame: 12 weeks
This is a measurement of vascular stiffness
12 weeks
Change in serum Soluble Suppression Tumorigenesis (SST2)
Time Frame: 12 weeks
This measures cardiac fibrosis
12 weeks
Peak flow velocity
Time Frame: 12 weeks
This is a measurement of vascular stiffness
12 weeks
Peak Hyperemic Shear Stress of Brachial Artery
Time Frame: 12 weeks
This is a measurement of vascular stiffness
12 weeks
Change in Galectin-3
Time Frame: 12 weeks
This measures cardiac fibrosis
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical College of Wisconsin

Collaborators

Advancing a Healthier Wisconsin

Investigators

  • Principal Investigator: Michael E Widlansky, MD, Medical College of Wisconsin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 Major Dates

Study Start (Actual)

February 20, 2023

Primary Completion (Actual)

March 31, 2025

Study Completion (Actual)

March 1, 2026

Study Registration Dates

First Submitted

February 21, 2023

First Submitted That Met QC Criteria

February 21, 2023

First Posted (Actual)

March 3, 2023

Study Record Updates

Last Update Posted (Actual)

May 1, 2026

Last Update Submitted That Met QC Criteria

April 27, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 45284

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Time Frame

Within 1 year of completion of all studies procedures

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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