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Completed

NCT Number: NCT05917873

Metabolic Effects of Four-week Lactate-ketone Ester Supplementation

Recent research reveals intriguing results concerning the role of exogenous lactate and the ketone body 3-hydroxybutyrate (3-OHB) as therapeutic tools to combat obesity and related conditions. Thus, oral administration of lactate and 3-OHB have separately been shown to suppress appetite sensations and slow gastric emptying while administered orally. Both seem to inhibit lipolysis while oral 3-OHB administration have shown direct insulin sensitizing effects. Furthermore, both substrates can be used as fuel for the heart.

The goal of this placebo-controlled randomized crossover design is to test exogenous lactate and the ketone body 3-hydroxybutyrate (3-OHB) in healthy, non-diabetic, obese adults.

The main questions it aims to answer are if chronic administration of LaKe ester affect or improve the following endpoints:

* Insulin sensitivity * Appetite sensations * Gastric emptying * Lipolysis * Cardiac output * Left Ventricular Ejection Fraction * Global Longitudinal Strain and other echocardiographic measures listed below

Participants will ingest a combined lactate and ketone body ester (LaKe ester) or placebo twice a day for 28 days before experimental days.

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Key information

Conditions

Obesity Body Weight Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

30 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Steno Diabetes Center Aarhus

Aarhus, 8200, Denmark

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age between 30-60 years
  • BMI range 30-40
  • Glycated haemoglobin (HbA1c) < 48 mmol/mol
  • Otherwise 'healthy'
  • Written and oral consent

Exclusion criteria

  • Medication that affect energy or glucose metabolism, eg metformin, insulin or Glucagon-like peptide-1 receptor (GLP-1) agonists
  • Specific diets (eg practicing ketogenic diets)
  • Cardiac arrhythmias (eg atrial fibrillation)
  • Ongoing acute/chronic serious diseases (eg, anemia, chronic kidney or liver disease)
  • Inability to understand Danish or English

Treatment and study plan

LaKe Ester

Dietary Supplement

Lactate and ketone body ester (one equivalent of S-lactate and one equivalent of 1,3-butanediol / D-β-hydroxybutyrate)

Placebo

Dietary Supplement

Taste and appearance matched noncaloric placebo

Primary outcomes

  1. Insulin sensitivity expressed as an M-value

    Time frame: Throughout the cross-over design, approximately 12 weeks

    On all study days, a hyperinsulinemic-euglycemic clamp is used to determine insulin sensitivity: continuous infusion of insulin (1 milliunit · kg lean body mass-1 · min-1) for 2 hours. The blood glucose is clamped at 5 mmol/l.

Secondary outcomes

  1. Differences in lipolysis rate

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Measured as differences in palmitate flux

  2. Differences in body weight and composition

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Dual-energy X-ray absorptiometry (DEXA) scan to assess total fat mass (kg), lean body mass (kg), and bone mass (kg)

  3. Differences in gastric emptying rate

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Evaluated by using the acetaminophen test

  4. Cardiac Output (CO)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Echocardiographic changes in left ventricular outflow tract (LVOT), velocity time integral (VTI) and heart rate (HR)

  5. Left Ventricular Ejection Fraction (LVEF)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Echocardiographic changes

  6. Tricuspid annular plane systolic excursion (TAPSE)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Echocardiographic changes

  7. Global Longitudinal Strain (GLS)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Echocardiographic changes

  8. Mitral inflow velocities (E and A)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Echocardiographic changes

  9. Mitral plane velocities in the lateral mitral annulus (e' and s')

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Echocardiographic changes

  10. Global work index (GWI)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Echocardiographic changes

  11. Changes in blood concentrations of 3-OHB

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  12. Changes in blood concentrations of lactate

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  13. Changes in blood concentrations of free fatty acids

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  14. Changes in blood concentrations of glucose

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  15. Changes in blood concentrations of insulin

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  16. Changes in plasma concentrations of growth/differentiation factor 15 (GDF-15)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  17. Changes in blood concentrations of gastric inhibitory polypeptide (GIP)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  18. Changes in blood concentrations of ghrelin

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  19. Changes in blood concentrations of glucagon

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  20. Changes in blood concentrations of liver-expressed antimicrobial peptide 2 (LEAP-2)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  21. Changes in blood concentrations of C-peptide

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  22. Changes in blood concentrations of triglycerides

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  23. Changes in blood concentrations of cholesterol

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  24. Changes in blood concentrations of brain-derived neurotrophic factor (BDNF)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  25. Changes in blood concentrations of N-lactoyl-phenylalanine (Lac-Phe)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  26. Fibrosis-4 (FIB-4)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling of alanine aminotransferase (ALAT), aspartate transaminase (ASAT), and thrombocytes

  27. Changes in blood concentrations of erythrocyte volume fraction (EVF)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  28. Changes in blood concentrations of Erythropoietin (EPO)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling

  29. Changes in blood concentrations of inflammation markers

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Blood sampling of C reactive protein (CRP) and leucocytes

  30. Mood, assessed by Major Depression Inventory score (MDI)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Change in MDI score measured by Major Depression Inventory. The theoretical sum score ranges from 0 (no depression) to 50 (maximum depression).

  31. Anxiety Symptom Scale questionnaire (ASS)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Change in the Anxiety Symptom Scale questionnaire to screen for anxiety disorders. The theoretical sum score ranges from 0 (no anxiety) to 60 (maximum anxiety).

  32. Supplement tolerability

    Time frame: Throughout the cross-over design, approximately 12 weeks

    Assessed using a symptom questionnaire covering every organ system, including GI symptoms measured through the validated "Beverage Tolerability Questionnaire". Participants will rate the frequency of each item on a scale from 0 (no symptoms) to 5 (severe symptoms).

  33. Control of Eating Questionnaire (CoEQ)

    Time frame: Throughout the cross-over design, approximately 12 weeks

    The CoEQ has been used in clinical trials as a multi-dimensional measure of appetite, craving and mood regulation. Based on the previous 7 days, subjects will be asked to answer 21 questions (20 rated on a 100 mm visual analogue scale and one open-ended).

Sponsors and collaborators

Lead sponsor

University of Aarhus

Other

Collaborators

  • Aarhus University Hospital
  • Novo Nordisk A/S
  • Riisfort

Registry information

Acronym: MetaLaKe

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Jun 26, 2023
Registry last updated
Aug 28, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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