Obesity
Conditions
Keywords
Insulin sensitivity, Lipolysis, Appetite
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTLaKe Ester
Lactate and ketone body ester (one equivalent of S-lactate and one equivalent of 1,3-butanediol / D-β-hydroxybutyrate)
DIETARY_SUPPLEMENTPlacebo
Taste and appearance matched noncaloric placebo
Sponsors
Novo Nordisk A/S
Aarhus University Hospital
Riisfort
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin sensitivity expressed as an M-value | 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
| Measure | Time frame | Description |
|---|---|---|
| Differences in lipolysis rate | Throughout the cross-over design, approximately 12 weeks | Measured as differences in palmitate flux |
| Differences in body weight and composition | 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) |
| Differences in gastric emptying rate | Throughout the cross-over design, approximately 12 weeks | Evaluated by using the acetaminophen test |
| Cardiac Output (CO) | Throughout the cross-over design, approximately 12 weeks | Echocardiographic changes in left ventricular outflow tract (LVOT), velocity time integral (VTI) and heart rate (HR) |
| Left Ventricular Ejection Fraction (LVEF) | Throughout the cross-over design, approximately 12 weeks | Echocardiographic changes |
| Tricuspid annular plane systolic excursion (TAPSE) | Throughout the cross-over design, approximately 12 weeks | Echocardiographic changes |
| Global Longitudinal Strain (GLS) | Throughout the cross-over design, approximately 12 weeks | Echocardiographic changes |
| Mitral inflow velocities (E and A) | Throughout the cross-over design, approximately 12 weeks | Echocardiographic changes |
| Mitral plane velocities in the lateral mitral annulus (e' and s') | Throughout the cross-over design, approximately 12 weeks | Echocardiographic changes |
| Global work index (GWI) | Throughout the cross-over design, approximately 12 weeks | Echocardiographic changes |
| Changes in blood concentrations of 3-OHB | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of lactate | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of free fatty acids | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of glucose | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of insulin | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in plasma concentrations of growth/differentiation factor 15 (GDF-15) | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of gastric inhibitory polypeptide (GIP) | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of ghrelin | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of glucagon | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of liver-expressed antimicrobial peptide 2 (LEAP-2) | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of C-peptide | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of triglycerides | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of cholesterol | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of brain-derived neurotrophic factor (BDNF) | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of N-lactoyl-phenylalanine (Lac-Phe) | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Fibrosis-4 (FIB-4) | Throughout the cross-over design, approximately 12 weeks | Blood sampling of alanine aminotransferase (ALAT), aspartate transaminase (ASAT), and thrombocytes |
| Changes in blood concentrations of erythrocyte volume fraction (EVF) | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of Erythropoietin (EPO) | Throughout the cross-over design, approximately 12 weeks | Blood sampling |
| Changes in blood concentrations of inflammation markers | Throughout the cross-over design, approximately 12 weeks | Blood sampling of C reactive protein (CRP) and leucocytes |
| Mood, assessed by Major Depression Inventory score (MDI) | 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). |
| Anxiety Symptom Scale questionnaire (ASS) | 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). |
| Supplement tolerability | 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). |
| Control of Eating Questionnaire (CoEQ) | 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). |
Countries
Denmark
Outcome results
None listed