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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GH infusion + oral ketone supplement | Experimental | Participants receive a continuous intravenous infusion of growth hormone (30 ng·kg-¹·min-¹) combined with oral ketone supplementation. |
|
| GH infusion + oral placebo | Experimental | Participants receive a continuous intravenous infusion of growth hormone (30 ng·kg-¹·min-¹) combined with oral placebo |
|
| Saline infusion + oral ketone supplement | Experimental | Participants receive an intravenous saline infusion combined with oral ketone supplementation. |
|
| Saline infusion + oral placebo | Placebo Comparator | Participants receive a continuous intravenous infusion of saline combined with oral placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Growth Hormone, Human | Drug | Continuous intravenous infusion of growth hormone (30 ng·kg-¹·min-¹) for approximately 7 hours to induce physiological lipolysis. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | During four experimental study days conducted over approximately 12 weeks |
| 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. | During four experimental study days conducted over approximately 12 weeks |
| 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. | During four experimental study days conducted over approximately 12 weeks |
| Energy expenditure | Measurement of resting and insulin-stimulated energy expenditure using indirect calorimetry and analysis of respiratory exchange ratio (RER). | During four experimental study days conducted over approximately 12 weeks |
| Cardiac output measured by PET/CT imaging | 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. | During four experimental study days conducted over approximately 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | During four experimental study days conducted over approximately 12 weeks |
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Inclusion Criteria:
Exclusion Criteria:
- Any evidence of acute or chronic illnesses, apart from well-controlled hypertension, that is judged by the investigators to impact the study
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Simon Bøggild Hansen, MD | Contact | +45 4111 1574 | simhan@clin.au.dk |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aarhus University Hospital | Recruiting | Aarhus N | 8200 | Denmark |
Individual participant data (IPD) will not be shared due to the small sample size, risk of indirect participant identification, and national data protection regulations (GDPR and Danish Data Protection Act). Aggregated and anonymized summary data will be available upon reasonable request.
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D009765 | Obesity |
| D050177 | Overweight |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D019382 | Human Growth Hormone |
| ID | Term |
|---|---|
| D013006 | Growth Hormone |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
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| 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. |
|
| Myocardial glucose and fatty acid uptake rates | 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. | During four experimental study days conducted over approximately 12 weeks |
| 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. |
| During four experimental study days conducted over approximately 12 weeks |
| Expression levels of lipolytic regulatory proteins in adipose tissue | Expression of regulators of lipolysis to assess GH- and BHB-mediated effects on lipid metabolism. | During four experimental study days conducted over approximately 12 weeks |
| Phosphorylation levels of insulin-regulated proteins in skeletal muscle | Quantification of phosphorylation levels of insulin-regulated proteins in skeletal-muscle biopsies. | During four experimental study days conducted over approximately 12 weeks |
| Expression levels of insulin-regulated proteins in skeletal muscle | Quantification of protein expression levels of insulin-regulated proteins in skeletal-muscle biopsies. | During four experimental study days conducted over approximately 12 weeks |
| Expression levels of GH-regulated proteins (GHR, JAK2, STAT5, BCL6) in skeletal muscle and adipose tissue | Quantification of GH-regulated proteins (GHR, JAK2, STAT5, BCL6) in muscle and adipose biopsies using capillary electrophoresis immunoassay for each intervention condition. | During four experimental study days conducted over approximately 12 weeks |
| Relative mRNA expression of GH-responsive genes (SOCS1-3, CISH, IGF-I) in skeletal muscle and adipose tissue | 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. | During four experimental study days conducted over approximately 12 weeks |
| Skeletal muscle mitochondrial oxidative phosphorylation capacity | Assessment of mitochondrial oxidative phosphorylation capacity in permeabilized muscle fibers obtained from vastus lateralis biopsies, measured by high-resolution respirometry (Oroboros Oxygraph-2k). | During four experimental study days conducted over approximately 12 weeks |
| Muscle glycogen content | Measurement of skeletal-muscle glycogen stores to assess substrate utilization and glucose storage during growth-hormone and ketone interventions. | During four experimental study days conducted over approximately 12 weeks |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |