Effects of Ketone Bodies on Insulin Sensitivity
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age55-70
SponsorUniversity of Aarhus
About this trial
KETO-SENSE is a clinical research study investigating how ketone bodies affect energy metabolism and insulin sensitivity in humans. Ketone bodies are naturally produced by the liver during fasting or prolonged exercise and can serve as an alternative fuel for the brain, heart, and muscles.
In this study, ten overweight but otherwise healthy adults aged 55-70 years will participate in four study days at Aarhus University Hospital. Participants will receive one of four interventions in a randomized crossover design: 1) growth hormone (GH) and a ketone supplement, 2) GH and placebo, 3) a saline infusion with the ketone supplement, or 4) placebo (saline infusion and placebo supplement). The study uses advanced PET/CT imaging, indirect calorimetry, and tissue biopsies to measure how ketones influence fat breakdown, glucose uptake, and energy expenditure.
By understanding these mechanisms, the study aims to clarify whether oral ketone supplementation can improve insulin sensitivity and energy metabolism - findings that could be relevant for common conditions such as overweight, insulin resistance, and type 2 diabetes.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age range: 55-70 yr
BMI: 25 - 35 kg/m2
Disqualifiers
None
Trial design
Design model
Crossover
Treatments tested in this trial
Growth Hormone, Human
DrugContinuous intravenous infusion of growth hormone (30 ng·kg-¹·min-¹) for approximately 7 hours to induce physiological lipolysis.
Oral ketone supplement (KetoAid®, KE4)
Dietary supplementOral administration of D-β-hydroxybutyrate ester (R-1,3-butanediol β-hydroxybutyrate).
Saline infusion (placebo)
DrugContinuous IV infusion of isotonic saline as placebo for growth hormone.
Oral placebo drink
Dietary supplementOral administration of an isocaloric placebo drink.
Treatment groups
10 Participants
are divided into 4 treatment groupsGroup A: GH infusion + oral ketone supplementExperimental treatment 2 interventions
Group B: GH infusion + oral placeboExperimental treatment 2 interventions
Group C: Saline infusion + oral ketone supplementExperimental treatment 2 interventions
Group D: Saline infusion + oral placeboPlacebo comparator 2 interventions
Trial outcomes
Primary outcomes
1
Insulin-stimulated glucose uptake in skeletal muscle and organs measured by [¹⁸F]-FDG PET
Quantification of insulin-stimulated glucose uptake rates in skeletal muscle and selected organs using dynamic \[¹⁸F\]-FDG PET during a hyperinsulinemic-euglycemic clamp to assess insulin sensitivity.
Time frame
During four experimental study days conducted over approximately 12 weeks2
Tissue-specific uptake of β-hydroxybutyrate and palmitate measured by PET/CT imaging
Quantification of tissue-specific uptake of β-hydroxybutyrate (BHB) and palmitate in skeletal muscle, adipose tissue, and myocardium using dynamic PET/CT imaging with \[¹¹C\]-OHB and \[¹¹C\]-palmitate tracers.
Time frame
During four experimental study days conducted over approximately 12 weeks3
Tissue-specific oxidation of β-hydroxybutyrate and palmitate measured by PET/CT imaging
Quantification of oxidation rates of β-hydroxybutyrate (BHB) and palmitate in skeletal muscle, adipose tissue, and myocardium using dynamic PET/CT imaging with \[¹¹C\]-OHB and \[¹¹C\]-palmitate tracers to assess tissue-specific substrate utilization.
Time frame
During four experimental study days conducted over approximately 12 weeks4
Energy expenditure
Measurement of resting and insulin-stimulated energy expenditure using indirect calorimetry and analysis of respiratory exchange ratio (RER).
Time frame
During four experimental study days conducted over approximately 12 weeksSecondary outcomes
1
Skeletal muscle pyruvate dehydrogenase (PDHa) enzymatic activity
Assessment of skeletal-muscle PDHa enzymatic activity determined from the rate of acetyl-CoA production using a radioactivity-based assay and normalized to creatine content in the muscle homogenate.
Time frame
During four experimental study days conducted over approximately 12 weeks2
Adipose tissue lipoprotein lipase (LPL) enzymatic activity
Determination of heparin-releasable LPL activity in subcutaneous adipose-tissue and muscle biopsies using the glycerol-stabilized method to evaluate triglyceride-derived fatty-acid uptake.
Time frame
During four experimental study days conducted over approximately 12 weeks3
Expression levels of lipolytic regulatory proteins in adipose tissue
Expression of regulators of lipolysis to assess GH- and BHB-mediated effects on lipid metabolism.
Time frame
During four experimental study days conducted over approximately 12 weeks4
Phosphorylation levels of insulin-regulated proteins in skeletal muscle
Quantification of phosphorylation levels of insulin-regulated proteins in skeletal-muscle biopsies.
Time frame
During four experimental study days conducted over approximately 12 weeksSponsors and contacts
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Source ClinicalTrials.gov