Physiological Effects of Lactate in Individuals With Chronic Heart Failure

March 27, 2024 updated by: Henrik Wiggers

Background:

Lactate is continuously produced in the human body through two primary processes: glycolysis and microbial fermentation in the gastrointestinal tract. At rest, its concentration in the bloodstream typically ranges from 1 to 2 mmol/L. However, during periods of physical exertion or insufficient oxygen supply, such as during intense exercise, lactate levels significantly increase. Traditionally, lactate was perceived as a byproduct of anaerobic metabolism. Nevertheless, emerging research has illuminated its vital role as both a signaling molecule and a crucial energy source for vital organs like skeletal muscle, brain, and the heart.

Objectives:

The primary aim of this study is to investigate the impact of physiological levels of circulating lactate on the hemodynamics of individuals with chronic heart failure. This research seeks to understand how lactate affects the cardiovascular response in this specific patient population.

Design and Endpoints:

The study design employs a double-blind, randomized crossover approach involving 12 heart failure patients. Each participant will undergo two separate visits.

Visit 1: Participants will receive a three-hour intravenous infusion of either a racemic (D/L) mixture of sodium lactate or an intravenous isotonic sodium chloride placebo, with a subsequent crossover to the opposite infusion on the same day.

Visit 2: Similar to the first visit, participants will receive either an orally administered racemic (D/L) mixture of sodium lactate or an isocaloric, isovolumic oral placebo (maltodextrin), with a crossover to the opposite administration after three hours.

The study's endpoints include cardiac output (primary), mixed venous saturation (SVO2), pulmonary wedge pressure, resting echocardiography (left ventricular ejection fraction and myocardial work efficiency), and measurements of vasoactive substances in blood samples.

Methods:

The study employs invasive Swan-Ganz monitoring to measure cardiac output, echocardiography, and frequent venous blood sample collections. These measurements and samples will be taken at specific intervals during the study visits.

Intervention:

To investigate the isolated hemodynamic and physiological effects of lactate, the study utilizes lactate infusion and ingestion to induce a state of hyperlactatemia within the physiological range. The intended dosages aim to stay within the physiological range, with no values expected to exceed 3-4 mmol/L.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

12

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 Contact

  • Name: Niels A. Jespersen, MD
  • Phone Number: +45 22950990
  • Email: nije@clin.au.dk

Study Contact Backup

Study Locations

  • Denmark
    • Region Midtjylland
      • Aarhus, Region Midtjylland, Denmark, 8200
        • Recruiting
        • Aarhus University Hospital
        • Contact:
          • Niels A. Jespersen, MD
          • Phone Number: +4522950990
          • Email: nijesp@rm.dk
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Chronic heart failure
  • NYHA II-III
  • Left ventricular ejection fraction <40%
  • Negative urine-HCG for women with childbearing potential

Exclusion Criteria:

  • Diabetes or HbA1c >48 mmol/mol
  • Significant cardiac valve disease
  • Severe stable angina pectoris
  • Severe comorbidity as judged by the investigator
  • Inability to give informed consent
  • Age <18 years
  • Other disease or treatment making subject unsuitable for study participation as judged by the investigator.

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: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Lactate infusion
All participants will be randomized to first receive a three-hour intravenous infusion with either a racemic (D/L) mixture of sodium lactate or intravenous isotonic sodium chloride placebo. All participants will then cross over to the converse infusion on the same day.
Other: Sodium lactate infusion
Dosage of sodium-lactate: 0.5 mol/L; 3 mL/kg/time; maximal 300 mL/hour.
Active Comparator: Lactate ingestion
All participants will be randomized to first receive either an orally administered racemic (D/L) mixture of sodium lactate or isocaloric, isovolumic oral placebo (maltodextrin). The oral dose of lactate will be equal to the intravenous dose. All participants will be studied for three hours and then cross over to receive the converse oral administration following additional three hours of observation time on the same day.
Other: Sodium lactate ingestion
Oral dose is equal to the i.v. dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiac output Cardiac output
Time Frame: Two visits of six hours each separated by a one-week washout period. Thus, outcome measures for the intravenous route will be assessed at week one, and outcome measures for the oral route will be assessed at week 2.

Unit: L/min.

It represents the amount of blood that the heart pumps out of the left ventricle per minute.
Two visits of six hours each separated by a one-week washout period. Thus, outcome measures for the intravenous route will be assessed at week one, and outcome measures for the oral route will be assessed at week 2.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mixed venous saturation (SVO2)
Time Frame: Two visits of six hours each separated by a one-week washout period. Thus, outcome measures for the intravenous route will be assessed at week one, and outcome measures for the oral route will be assessed at week 2.

Unit: %

It represents the percentage of oxygen saturation in the blood as it returns to the right side of the heart after circulating through the body's tissues.
Two visits of six hours each separated by a one-week washout period. Thus, outcome measures for the intravenous route will be assessed at week one, and outcome measures for the oral route will be assessed at week 2.
Pulmonary wedge pressure
Time Frame: Two visits of six hours each separated by a one-week washout period. Thus, outcome measures for the intravenous route will be assessed at week one, and outcome measures for the oral route will be assessed at week 2.

Unit: mmHg

It reflects the pressure within the left atrium and the left ventricle of the heart, and it is an important indicator of left ventricular preload.
Two visits of six hours each separated by a one-week washout period. Thus, outcome measures for the intravenous route will be assessed at week one, and outcome measures for the oral route will be assessed at week 2.
Left ventricular ejection fraction
Time Frame: Two visits of six hours each separated by a one-week washout period. Thus, outcome measures for the intravenous route will be assessed at week one, and outcome measures for the oral route will be assessed at week 2.

Unit: %

It is a measure of the percentage of blood that is pumped out of the left ventricle with each heartbeat.
Two visits of six hours each separated by a one-week washout period. Thus, outcome measures for the intravenous route will be assessed at week one, and outcome measures for the oral route will be assessed at week 2.
Global longitudinal strain
Time Frame: Two visits of six hours each separated by a one-week washout period. Thus, outcome measures for the intravenous route will be assessed at week one, and outcome measures for the oral route will be assessed at week 2.

Unit: %

It quantifies the deformation or shortening of the heart muscle fibers along the longitudinal (lengthwise) axis of the left ventricle during the cardiac cycle.
Two visits of six hours each separated by a one-week washout period. Thus, outcome measures for the intravenous route will be assessed at week one, and outcome measures for the oral route will be assessed at week 2.

Collaborators and Investigators

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

Sponsor

Henrik Wiggers

Investigators

  • Study Chair: Henrik Wiggers, Professor, Dept. of Cardiology, Aarhus University Hospital

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)

November 22, 2023

Primary Completion (Estimated)

September 30, 2024

Study Completion (Estimated)

September 30, 2024

Study Registration Dates

First Submitted

September 20, 2023

First Submitted That Met QC Criteria

November 1, 2023

First Posted (Actual)

November 7, 2023

Study Record Updates

Last Update Posted (Actual)

March 28, 2024

Last Update Submitted That Met QC Criteria

March 27, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LACTATE-CHF

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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