Physiological Effects of Lactate in Individuals With Chronic Heart Failure

Not Applicable

Recruiting

• Conditions: Heart Failure, Systolic

• Registration Number: NCT06121323
• Lead Sponsor: Henrik Wiggers

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-20
• Study First Submitted QC: 2023-11-01
• Study First Posted: 2023-11-07
• Study Start: 2023-11-22
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-27
• Last Update Posted: 2024-03-28
• Primary Completion: 2024-09-30
• Study Completion: 2024-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Cardiac output Cardiac output	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.

Secondary Outcome Measures

Name	Time	Method
Mixed venous saturation (SVO2)	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.
Pulmonary wedge pressure	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.
Global longitudinal strain	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.
Left ventricular ejection fraction	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.

Trial Locations

Locations (1)

Aarhus University Hospital; 🇩🇰 Aarhus, Region Midtjylland, Denmark