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NCT Number: NCT07359625

Effects of Ketone Bodies on Insulin Sensitivity

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.

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Key information

Conditions

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

Age range

55 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Aarhus University Hospital

Aarhus N, 8200, Denmark

Location status: Recruiting

Location contact

Simon Bøggild Hansen, MD

CONTACT

[email protected]

+45 4111 1574

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Age range: 55-70 yr
  • BMI: 25 - 35 kg/m2

Exclusion criteria

  • Any evidence of acute or chronic illnesses, apart from well-controlled hypertension, that is judged by the investigators to impact the study

Treatment and study plan

Growth Hormone, Human

Drug

Continuous 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 Supplement

Oral administration of D-β-hydroxybutyrate ester (R-1,3-butanediol β-hydroxybutyrate).

Saline infusion (placebo)

Drug

Continuous IV infusion of isotonic saline as placebo for growth hormone.

Oral placebo drink

Dietary Supplement

Oral administration of an isocaloric placebo drink.

Primary outcomes

  1. Insulin-stimulated glucose uptake in skeletal muscle and organs measured by [¹⁸F]-FDG PET

    Time frame: During four experimental study days conducted over approximately 12 weeks

    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.

  2. Tissue-specific uptake of β-hydroxybutyrate and palmitate measured by PET/CT imaging

    Time frame: During four experimental study days conducted over approximately 12 weeks

    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.

  3. Tissue-specific oxidation of β-hydroxybutyrate and palmitate measured by PET/CT imaging

    Time frame: During four experimental study days conducted over approximately 12 weeks

    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.

  4. Energy expenditure

    Time frame: During four experimental study days conducted over approximately 12 weeks

    Measurement of resting and insulin-stimulated energy expenditure using indirect calorimetry and analysis of respiratory exchange ratio (RER).

  5. Cardiac output measured by PET/CT imaging

    Time frame: During four experimental study days conducted over approximately 12 weeks

    Quantification of cardiac output in the basal state and during the hyperinsulinemic-euglycemic clamp using dynamic PET/CT imaging to evaluate hemodynamic effects of GH and β-hydroxybutyrate.

  6. Myocardial glucose and fatty acid uptake rates

    Time frame: During four experimental study days conducted over approximately 12 weeks

    Assessment of myocardial substrate metabolism using dynamic PET/CT imaging with [¹⁸F]-FDG and [¹¹C]-palmitate tracers during the basal period and the hyperinsulinemic-euglycemic clamp to quantify myocardial utilization of glucose and fatty acids.

Secondary outcomes

  1. Skeletal muscle pyruvate dehydrogenase (PDHa) enzymatic activity

    Time frame: During four experimental study days conducted over approximately 12 weeks

    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.

  2. Adipose tissue lipoprotein lipase (LPL) enzymatic activity

    Time frame: During four experimental study days conducted over approximately 12 weeks

    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.

  3. Expression levels of lipolytic regulatory proteins in adipose tissue

    Time frame: During four experimental study days conducted over approximately 12 weeks

    Expression of regulators of lipolysis to assess GH- and BHB-mediated effects on lipid metabolism.

  4. Phosphorylation levels of insulin-regulated proteins in skeletal muscle

    Time frame: During four experimental study days conducted over approximately 12 weeks

    Quantification of phosphorylation levels of insulin-regulated proteins in skeletal-muscle biopsies.

  5. Expression levels of insulin-regulated proteins in skeletal muscle

    Time frame: During four experimental study days conducted over approximately 12 weeks

    Quantification of protein expression levels of insulin-regulated proteins in skeletal-muscle biopsies.

  6. Expression levels of GH-regulated proteins (GHR, JAK2, STAT5, BCL6) in skeletal muscle and adipose tissue

    Time frame: During four experimental study days conducted over approximately 12 weeks

    Quantification of GH-regulated proteins (GHR, JAK2, STAT5, BCL6) in muscle and adipose biopsies using capillary electrophoresis immunoassay for each intervention condition.

  7. Relative mRNA expression of GH-responsive genes (SOCS1-3, CISH, IGF-I) in skeletal muscle and adipose tissue

    Time frame: During four experimental study days conducted over approximately 12 weeks

    Quantification of GH-responsive gene expression (SOCS1-3, CISH, IGF-I) in muscle and adipose biopsies using RT-PCR. Relative mRNA expression will be reported as fold change for each intervention condition.

  8. Skeletal muscle mitochondrial oxidative phosphorylation capacity

    Time frame: During four experimental study days conducted over approximately 12 weeks

    Assessment of mitochondrial oxidative phosphorylation capacity in permeabilized muscle fibers obtained from vastus lateralis biopsies, measured by high-resolution respirometry (Oroboros Oxygraph-2k).

  9. Muscle glycogen content

    Time frame: During four experimental study days conducted over approximately 12 weeks

    Measurement of skeletal-muscle glycogen stores to assess substrate utilization and glucose storage during growth-hormone and ketone interventions.

Study contacts

Contact information is provided by the study sponsor or research team.

Simon Bøggild Hansen, MD

CONTACT

[email protected]

+45 4111 1574

Sponsors and collaborators

Lead sponsor

University of Aarhus

Other

Registry information

Official study title

KETO-SENSE - Effects of Ketone Bodies on Insulin Sensitivity

Acronym: KETO-SENSE

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Jan 22, 2026
Registry last updated
Jan 22, 2026

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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