Effects of Ketone Bodies on Insulin Sensitivity

NCT07359625 | Recruiting

• 1 other identifier: KETO-SENSE
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Insulin Resistance; Obesity & Overweight; Energy Metabolism; Ketone Body Metabolism

Keywords

insulin resistance; Overweight; Growth hormone; Ketone bodies; Lipolysis; Energy metabolism

Outcome Measures

Primary Outcomes (6)

• 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

• 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

Secondary Outcomes (9)

• Skeletal muscle pyruvate dehydrogenase (PDHa) enzymatic activity

  During four experimental study days conducted over approximately 12 weeks

• Adipose tissue lipoprotein lipase (LPL) enzymatic activity

  During four experimental study days conducted over approximately 12 weeks

• Expression levels of lipolytic regulatory proteins in adipose tissue

  During four experimental study days conducted over approximately 12 weeks

• Phosphorylation levels of insulin-regulated proteins in skeletal muscle

  During four experimental study days conducted over approximately 12 weeks

• Expression levels of insulin-regulated proteins in skeletal muscle

  During four experimental study days conducted over approximately 12 weeks

Study Arms (4)

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.

Drug: Growth Hormone, Human; Dietary Supplement: Oral ketone supplement (KetoAid®, KE4)

GH infusion + oral placebo

EXPERIMENTAL

Participants receive a continuous intravenous infusion of growth hormone (30 ng·kg-¹·min-¹) combined with oral placebo

Drug: Growth Hormone, Human; Dietary Supplement: Oral placebo drink

Saline infusion + oral ketone supplement

EXPERIMENTAL

Participants receive an intravenous saline infusion combined with oral ketone supplementation.

Dietary Supplement: Oral ketone supplement (KetoAid®, KE4); Drug: Saline infusion (placebo)

Saline infusion + oral placebo

PLACEBO COMPARATOR

Participants receive a continuous intravenous infusion of saline combined with oral placebo

Drug: Saline infusion (placebo); Dietary Supplement: Oral placebo drink

Interventions

Growth Hormone, Human DRUG

Continuous intravenous infusion of growth hormone (30 ng·kg-¹·min-¹) for approximately 7 hours to induce physiological lipolysis.

GH infusion + oral ketone supplement; GH infusion + oral placebo

Oral ketone supplement (KetoAid®, KE4) DIETARY_SUPPLEMENT

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

GH infusion + oral ketone supplement; Saline infusion + oral ketone supplement

Saline infusion (placebo) DRUG

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

Saline infusion + oral ketone supplement; Saline infusion + oral placebo

Oral placebo drink DIETARY_SUPPLEMENT

Oral administration of an isocaloric placebo drink.

GH infusion + oral placebo; Saline infusion + oral placebo

Eligibility Criteria

• Age: 55 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University Hospital

Aarhus N, 8200, Denmark

RECRUITING

MeSH Terms

Conditions

Insulin Resistance; Obesity; Overweight

Interventions

Human Growth Hormone

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Growth Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Simon Bøggild Hansen, MD

CONTACT

+45 4111 1574; simhan@clin.au.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: January 22, 2026
• Study Start: December 2, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: January 22, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)