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

• ClinicalTrials.gov Identifier: NCT04710875
• Recruitment Status: Recruiting
• First Posted: January 15, 2021
• Last Update Posted: January 15, 2021
• Sponsor: University of Aarhus
• Information provided by (Responsible Party): University of Aarhus

Tracking Information

• First Submitted Date: December 1, 2020
• First Posted Date: January 15, 2021
• Last Update Posted Date: January 15, 2021
• Estimated Study Start Date: February 1, 2021
• Estimated Primary Completion Date: April 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 12, 2021)

Acute Metabolic effects of Na-lactate compared with NaCl on lipolysis [ Time Frame: 2 hours (1 hour basal period, 1 hour clamp) ]

Change in [9,10-3H]-palmitate tracer flux

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: January 12, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Role of Lactate in Lipolysis and Catabolism in Humans
• Official Title: The Role of Lactate in Lipolysis and Catabolism in Humans

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Single (Participant); Primary Purpose: Other

Condition

• Hyperlactatemia
• Healthy
• Lactate

Intervention

• Drug: Na-lactate
  intravenous
  Other Name: Sodium lactate
• Drug: Sodium chloride
  Intravenous
  Other Name: NaCl

Study Arms

• Active Comparator: Na-lactate
  Iv infusion of sodium D/L lactate
  Intervention: Drug: Na-lactate
• Placebo Comparator: Sodium chloride
  Iv infusion of Sodium chloride
  Intervention: Drug: Sodium chloride

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 12, 2021): 8
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 30, 2021
• Estimated Primary Completion Date: April 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Mette GB Pedersen, MD; 40857288; metteglavind@clin.au.dk

• Listed Location Countries: Denmark

Administrative Information

• NCT Number: NCT04710875
• Other Study ID Numbers: 1-10-72.180-20
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: University of Aarhus
• Study Sponsor: University of Aarhus
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Aarhus
• Verification Date: September 2020