Metabolic Effects of Four-week Lactate-ketone Ester Supplementation

Obesity Clinical Trial

— MetaLaKe  

Official title:

Metabolic Effects of Four-week Lactate-ketone Ester Supplementation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05917873
• Other study ID #: 98128
• Status: Recruiting
• Phase: N/A
• Start date: September 7, 2023
• Est. completion date: May 2025

Study information

• Verified date: April 2023
• Source: University of Aarhus
• Contact: Simon Kjær Simonsen, PhD student
• Phone: +45 28769491
• Email: simkjr[@]clin.au.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity

Intervention

Dietary Supplement:
• LaKe Ester
Lactate and ketone body ester (one equivalent of S-lactate and one equivalent of 1,3-butanediol / D-ß-hydroxybutyrate)
• Placebo
Taste and appearance matched noncaloric placebo

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center Aarhus	Aarhus

Sponsors (4)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital, Novo Nordisk A/S, Riisfort

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin sensitivity expressed as an M-value	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.	Throughout the cross-over design, approximately 12 weeks
Secondary	Differences in lipolysis rate	Measured as differences in palmitate flux	Throughout the cross-over design, approximately 12 weeks
Secondary	Differences in body weight and composition	Dual-energy X-ray absorptiometry (DEXA) scan to assess total fat mass (kg), lean body mass (kg), and bone mass (kg)	Throughout the cross-over design, approximately 12 weeks
Secondary	Differences in gastric emptying rate	Evaluated by using the acetaminophen test	Throughout the cross-over design, approximately 12 weeks
Secondary	Cardiac Output (CO)	Echocardiographic changes in left ventricular outflow tract (LVOT), velocity time integral (VTI) and heart rate (HR)	Throughout the cross-over design, approximately 12 weeks
Secondary	Left Ventricular Ejection Fraction (LVEF)	Echocardiographic changes	Throughout the cross-over design, approximately 12 weeks
Secondary	Tricuspid annular plane systolic excursion (TAPSE)	Echocardiographic changes	Throughout the cross-over design, approximately 12 weeks
Secondary	Global Longitudinal Strain (GLS)	Echocardiographic changes	Throughout the cross-over design, approximately 12 weeks
Secondary	Mitral inflow velocities (E and A)	Echocardiographic changes	Throughout the cross-over design, approximately 12 weeks
Secondary	Mitral plane velocities in the lateral mitral annulus (e' and s')	Echocardiographic changes	Throughout the cross-over design, approximately 12 weeks
Secondary	Global work index (GWI)	Echocardiographic changes	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of 3-OHB	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of lactate	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of free fatty acids	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of glucose	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of insulin	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in plasma concentrations of growth/differentiation factor 15 (GDF-15)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of gastric inhibitory polypeptide (GIP)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of ghrelin	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of glucagon	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of liver-expressed antimicrobial peptide 2 (LEAP-2)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of C-peptide	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of triglycerides	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of cholesterol	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of brain-derived neurotrophic factor (BDNF)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of N-lactoyl-phenylalanine (Lac-Phe)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Fibrosis-4 (FIB-4)	Blood sampling of alanine aminotransferase (ALAT), aspartate transaminase (ASAT), and thrombocytes	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of erythrocyte volume fraction (EVF)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of Erythropoietin (EPO)	Blood sampling	Throughout the cross-over design, approximately 12 weeks
Secondary	Changes in blood concentrations of inflammation markers	Blood sampling of C reactive protein (CRP) and leucocytes	Throughout the cross-over design, approximately 12 weeks
Secondary	Mood, assessed by Major Depression Inventory score (MDI)	Change in MDI score measured by Major Depression Inventory. The theoretical sum score ranges from 0 (no depression) to 50 (maximum depression).	Throughout the cross-over design, approximately 12 weeks
Secondary	Anxiety Symptom Scale questionnaire (ASS)	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).	Throughout the cross-over design, approximately 12 weeks
Secondary	Supplement tolerability	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).	Throughout the cross-over design, approximately 12 weeks
Secondary	Control of Eating Questionnaire (CoEQ)	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).	Throughout the cross-over design, approximately 12 weeks