The Role of Lactate in Lipolysis and Catabolism in Humans (LILACH)

Lactate may have anti-lipolytic effects when plasma concentrations of lactate reach levels similar to those seen during high intensity exercise.

This study aims to investigate how lactate concentrations similar to those achieved during high intensity exercise affects lipolysis in humans. In addition to this, to investigate how increased lactate concentrations affects glucose- and amino acid metabolism.

8 healthy males will be included. Study participants will undergo two separate investigation days that will be identical except for the interventions:

1. Intravenous sodium D/L-lactate
2. Intravenous sodium chloride.

The study consists of a 3-hour basal period followed by a 3-hour hyperinsulinemic euglycemic clamp. During the study we will:

• Estimate insulin sensitivity during the hyperinsulinemic euglycemic clamp (M value)
• Use tracer kinetics to estimate lipid-, glucose and amino acid metabolism using [9,10-3H]-palmitate, [3-3H]-glucose, [15N]-phenylalanine, [15N]-tyrosine, [2H4]-tyrosine and [13C]-Urea.
• Do muscle- and adipose tissue biopsies for analyses of signaling pathways involved in regulation of lipid-, glucose and amino acid metabolism.
• Do blood samples of relevant hormones, metabolites and cytokines.
• Use indirect calorimetry to estimate study participants' resting energy expenditure and respiratory quotient during the basal period.
• Estimate cardiac ejection fraction by echocardiography and measure blood pressure during both the basal- and clamp period.

Study Overview

• Status: Completed
• Conditions: Healthy; Hyperlactatemia; Lactate
• Intervention / Treatment: Drug: Na-lactate; Drug: Sodium chloride

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital
  • Central Region Denmark
    • Aarhus, Central Region Denmark, Denmark, 8200
      • Medical/Steno Aarhus research laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• male
• >18 years of age
• BMI >19 and below 30
• Written and verbal consent to participation

Exclusion Criteria:

• Chronic illness
• daily use of medicine
• affected blood samples at screening, as assessed by the PI
• does not speak and understand Danish
• Assessed unsuitable by PI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Na-lactate; Iv infusion of sodium D/L lactate	Drug: Na-lactate; intravenous; Other Names: Sodium lactate
PLACEBO_COMPARATOR: Sodium chloride; Iv infusion of Sodium chloride	Drug: Sodium chloride; Intravenous; Other Names: NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Metabolic effects of Na-lactate compared with NaCl on lipolysis	Change in [9,10-3H]-palmitate tracer flux	2 hours (1 hour basal period, 1 hour clamp)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Metabolic effects of Na-lactate compared with NaCl on glucose metabolism	Change in glucose metabolism quantified with [3-3H]-glucose tracer	6 hours (3 hours basal period, 3 hours clamp)
Insulin sensitivity	Hyperinsulinaemic euglycaemic clamp with 0.6mU/kg/min insulin and 20% glucose to calculate M value. Difference between interventions.	3 hours.
Acute metabolic effects of Na-lactate compared with NaCl on aminoacid metabolism	Change in aminoacid metabolism quantified with [15N]-phenylalanine, [15N]tyrosine, [2H4]tyrosine and [13C]-Urea tracers.	6 hours
Indirect calorimetry during clamp	Change in estimation of resting energy expenditure during clamp. Difference between interventions.	20 minutes
Indirect calorimetry during basal conditions	Change in estimation of respiratory quotient during basal period. Difference between interventions.	20 minutes
Echocardiography	Change in cardiac ejection fraction during basal period. Difference between interventions.	15 minutes
Echocardiography	Change in cardiac ejection fraction during clamp period. Difference between interventions.	15 minutes
blood pressure	blood pressure (systolic and diastolic) during basal- and clamp	2 x 10 min
Blood samples - Insulin	Insulin concentrations. Difference between interventions.	6 hours.
Blood samples - c-peptid	c-peptid concentrations. Difference between interventions.	6 hours.
Blood samples - glucagon	glucagon concentrations. Difference between interventions.	6 hours.
Blood samples - cortisol	cortisol concentrations. Difference between interventions.	6 hours.
Blood samples - Ghrelin	Ghrelin concentrations. Difference between interventions.	6 hours.
Blood samples - GDF-15	GDF-15 concentrations. Difference between interventions.	6 hours.
Blood samples - free fatte acids	Free fatte acids concentrations. Difference between interventions.	6 hours.
Blood samples - glucose	glucose concentrations. Difference between interventions.	6 hours.
Blood samples - lactate	lactate concentrations. Difference between interventions.	6 hours.
Changes in signaling in muscle tissue between interventions	Western blot examinations of muscle tissue biopsies	After 3 and 5 hours of intervention
Changes in signaling in adipose tissue between interventions	Western blot examinations of adipose tissue biopsies	After 3 and 5 hours of intervention

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Study Director: Niels Møller, Prof, MD, DMSc, Medical/Steno Aarhus research laboratory, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 10, 2021
• Primary Completion (ACTUAL): June 29, 2021
• Study Completion (ACTUAL): June 29, 2021

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (ACTUAL): January 15, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 21, 2022
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Lipolysis; Glucose metabolism; Catabolism; Aminoacid metabolisme
• Additional Relevant MeSH Terms: Metabolic Diseases; Hyperlactatemia
• Other Study ID Numbers: 1-10-72.180-20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No