Clinical trial NCT05917873: Metabolic Effects of Four-week Lactate-ketone Ester Supplementation
Official title: Metabolic Effects of Four-week Lactate-ketone Ester Supplementation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Obesity
Keywords: Insulin sensitivity
Lipolysis
Appetite
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
name: Aarhus University Hospital
name: Riisfort
First posted: 2023-06-26
Enrollment: 10
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Insulin sensitivity expressed as an M-value
timeFrame: Throughout the cross-over design, approximately 12 weeks
Secondary outcomes:
measure: Differences in lipolysis rate
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Differences in body weight and composition
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Differences in gastric emptying rate
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Cardiac Output (CO)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Tricuspid annular plane systolic excursion (TAPSE)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Global Longitudinal Strain (GLS)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Mitral inflow velocities (E and A)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Mitral plane velocities in the lateral mitral annulus (e' and s')
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Global work index (GWI)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of 3-OHB
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of lactate
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of free fatty acids
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of glucose
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of insulin
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in plasma concentrations of growth/differentiation factor 15 (GDF-15)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of gastric inhibitory polypeptide (GIP)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of ghrelin
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of glucagon
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of liver-expressed antimicrobial peptide 2 (LEAP-2)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of C-peptide
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of triglycerides
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of cholesterol
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of brain-derived neurotrophic factor (BDNF)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of N-lactoyl-phenylalanine (Lac-Phe)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Fibrosis-4 (FIB-4)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of erythrocyte volume fraction (EVF)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of Erythropoietin (EPO)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Changes in blood concentrations of inflammation markers
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Mood, assessed by Major Depression Inventory score (MDI)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Anxiety Symptom Scale questionnaire (ASS)
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Supplement tolerability
timeFrame: Throughout the cross-over design, approximately 12 weeks
measure: Control of Eating Questionnaire (CoEQ)
timeFrame: Throughout the cross-over design, approximately 12 weeks
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Steno Diabetes Center Aarhus
Study officials:
affiliation: Aarhus University Hospital
name: Niels Møller, Professor
role: STUDY_DIRECTOR
References: