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Completed

NCT Number: NCT04064268

Anabolic Potential of 3-hydroxybutyrate (3-OHB) and Whey Protein in a Human Catabolic Inflammatory Disease Model

This study aims to investigate the muscle anabolic potential of adding ketone (3-hydroxybutyrate) to whey protein compared with isocaloric, isonitrogenous whey protein in a human model of inflammatory catabolic disease. Further, this study aims to investigate whether the same amount of whey protein has different effects on muscles in an catabolic inflammatory setting compared with a healthy setting.

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Key information

Conditions

Endotoxemia Atrophy Bacteremia Catabolic State Disease Infections Inflammation Muscle Loss Muscular Atrophy Nervous System Diseases Neurologic Manifestations Neuromuscular Manifestations Nutrition Therapy Pathologic Processes Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Protein; Disease Sepsis Signs and Symptoms Systemic Inflammatory Response Syndrome Toxemia

Age range

20 year–40 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Medical Research Laboratory, DoH, Aarhus University Hospital

Aarhus, 8000, Denmark

About this study

Background: Muscle wasting during hospitalization is caused by a combination of immobilization (bed rest), hypocaloric diet and inflammation (e.g. sepsis), and preventive measures are needed. Whey protein is particularly potent in inducing muscle protein synthesis compared with other proteins, at least in healthy populations. Further, the ketone body 3-hydroxybutyrate (3-OHB) effectively preserved muscle in a model of acute inflammatory disease. However, little is known about whether 3-OHB can potentiate the effects of whey protein in a catabolic inflammatory setting.

Aim: This study aims to investigate the muscle anabolic potential of adding ketone (3-OHB) to whey protein compared with isocaloric, isonitrogenous whey protein in a human model of catabolic inflammatory disease. Further, this study aims to investigate whether the same amount of whey protein has different effects on muscles in an catabolic inflammatory setting compared with a healthy setting.

Hypothesis:

  • 3-OHB potentiates the effect of whey protein in maintaining muscle mass in a catabolic inflammatory setting.
  • The same amount of whey protein will have decreased muscle anabolic effects during catabolic inflammatory conditions compared with healthy conditions

Interventions:

In a randomized crossover design, eight healthy, lean, young men will undergo either:

i) Healthy conditions (overnight fast) + whey protein^ ii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest*) + whey protein^ iii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest*) + 3-OHB/whey protein^"

*LPS will be administered (1 ng/kg) the day prior to the study together with fast and bed rest. On the study day LPS (0.5 ng/kg) will be injected.

^Beverages will be isonitrogenous and isocaloric (fat will be added) with 45 g whey protein + 20 g maltodextrin. Bolus/sip administration will be applied (1/3 bolus, 1/2 sip)

" 50 grams of 3-OHB will be orally administered (1/2 bolus, 1/2 sip)

Before each study day:

The participants arrive fasting (only tap water allowed) by taxi on the study days. They have been without febrile disease the week prior to investigation, and have not performed exercise for 24 hours.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Between 20-40 years of age
  • Body mass index between 20-30 kg/m^2
  • Healthy
  • Oral and written consent forms obtained prior to study day

Exclusion criteria

  • Recent immobilization of an extremity that is not fully rehabilitated
  • Lactose, lidocain or rubber allergies
  • Current disease
  • Use of anabolic steroids
  • Smoking
  • Former major abdominal surgery (Or current problems with the GI tract)
  • >10 hours of exercise/weak
  • Present ketogenic diets or high-protein diets
  • Blood doner that does not want to discontinue blood donations until study completion
  • Pending MR scan

Treatment and study plan

Whey

Dietary Supplement

45 g whey + 20 g maltodextrin

3-OHB + Whey

Dietary Supplement

50 g ketone + 45 g whey + 20 g maltodextrin

Primary outcomes

  1. Change in forearm muscle kinetics measured by phenylalanine tracer (Netbalance, rate of disappearence and rate of apperance of phenylanine, nmol/100ml muscle/min)

    Time frame: Change from baseline to 3.5 hours after intervention

    Changes of forearm muscle phenylalanine kinetics from baseline to 3.5 hours after intervention using the forearm model

Secondary outcomes

  1. Change in concentration of total aminoacids

    Time frame: Change from baseline to 3.5 hours after intervention

    Change in total aminoacids from baseline to the end of the 3.5 hour sipping period

  2. Change in concentration of 3-hydroxybutyrate (mmol/L) )

    Time frame: Measured at baseline and every 30. min throughout the 3.5 hour sipping period

    Change in blood BHB levels from baseline to the end of the 3.5 hour sipping period (iAUC)

  3. Change in glucose kinetics measured by glucose tracer (rate of apperance and rate of disappearance, mg/kg/min)

    Time frame: Change from baseline to 3.5 hours after intervention

    Change in glucose kinetics from baseline to to the end of the 3.5 hour sipping period

  4. Change in concentration of plasma insulin

    Time frame: Measured at baseline and every 30. min throughout the 3.5 hour sipping period

    Change in plasma insulin levels from baseline to the end of the 3.5 hour sipping period (iAUC)

  5. Change in concentration of plasma glucose

    Time frame: Measured at baseline and every 30. min throughout the 3.5 hour sipping period

    Change in glucose levels from baseline and after 3.5 hour sipping period expressed as iAUC.

  6. Change in concentration of free fatty acids (FFA) levels

    Time frame: Change from baseline to 3.5 hours after intervention

    Change in FFA from baseline to the end of the sipping period

  7. Change in concentration of C-reactive peptide (CRP)

    Time frame: Change from baseline to 3.5 hours after intervention

    Change in CRP from baseline to the end of the sipping period

  8. Change in concentration of blood leucocytes (x10^9/L)

    Time frame: Change from baseline to 3.5 hours after intervention

    Change in leucocytes from baseline to the end of the sipping period

  9. Change in concentration of stress hormones (glucagon, cortisol, adrenalin, noradrenalin)

    Time frame: Change from baseline to 3.5 hours after intervention

    Change in hormones from baseline and after 3.5 hour sipping period

  10. Change in intracellular muscle signalling

    Time frame: Change from baseline to 3.5 hours after intervention

    Change in muscle signalling in muscle biopsies by western blot from baseline to the sipping period

  11. Difference in muscle forearm kinetics measured by phenylalanine tracer (Netbalance, rate of apperance, rate og disappearance) (healthy vs catabolic)

    Time frame: measured at the end of the 3.5 hour basal period

    Phenylalanine forearm kinetics measured by phenylalanine tracer at the end of the 3.5 hour basal period in healthy vs catabolic (pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)

  12. Difference in concentration of total amino acids (healthy vs catabolic)

    Time frame: measured at the end of the 3.5 hour basal period

    Total amino acids measured at the end of the 3.5 hour basal period in healthy vs catabolic conditions (pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)

  13. Difference in glucose kinetics measured with glucose tracer (mg/kg/min) (healthy vs catabolic)

    Time frame: measured at the end of the 3.5 hour basal period

    Glucose kinetics measured by glucose tracer at the end of the 3.5 hour basal period in healthy vs catabolic conditions (pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure)

  14. Difference in concentration of free fatty acids (FFA) (healthy vs catabolic)

    Time frame: Measured at the end of the 3.5 hour basal period.

    FFA measured at the end of the basal period in healthy vs catabolic (pooled mean of the two catabolic days)

  15. Difference in concentration of C-reactive peptide (CRP) (healthy vs catabolic)

    Time frame: Measured at the end of the 3.5 hour basal period.

    CRP measured at the end of the basal period in healthy vs catabolic (pooled mean of the two catabolic days)

  16. Difference in concentration of leucocytes (healthy vs catabolic)

    Time frame: Measured at the end of the 3.5 hour basal period.

    Leucocytes measured at the end of the basal period in healthy vs catabolic (pooled mean of the two catabolic days)

  17. Difference in intracellular muscle signalling (healthy vs catabolic)

    Time frame: Measured at the end of the 3.5 hour basal period.

    Muscle signalling measured in muscle biopsies by western blot during the 3.5 hour basal period in healthy vs catabolic (pooled mean of the two catabolic days)

  18. Difference in concentration of 3-hydroxybutyrate (mmol/L) (healthy vs catabolic)

    Time frame: Measured at the end of the 3.5 hour basal period.

    3-hydroxybutyrate measured at the end of the basal period in healthy vs catabolic (pooled mean of the two catabolic days)

  19. Difference in concentration of hormones (insulin, glucagon, cortisol, growth hormone, adrenaline, noradrenalin) (healthy vs catabolic)

    Time frame: Measured at the end of the 3.5 hour basal period.

    Hormones (insulin, glucagon, cortisol, growth hormone, adrenaline, noradrenalin) measured at the end of the basal period in healthy vs catabolic (pooled mean of the two catabolic days)

  20. Difference in whole body protein metabolism (healthy vs catabolic)

    Time frame: Measured at the end of the 3.5 hour basal period.

    Difference in whole body protein metabolism measured with tyrosine tracers at the end of the basal period in healthy vs catabolic (pooled mean of the two catabolic days)

  21. Difference in concentration of cytokines (healthy vs catabolic)

    Time frame: Measured at baseline and 120 and 240 minutes after LPS administration

    Cytokines (TNFalfa, IL-10, IL-6 and IL-1beta) measured between healthy and catabolic conditions (iAUC, a pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure))

  22. Difference in axillary temperature (healthy vs catabolic)

    Time frame: Measured at baseline and 1, 2, 3, 4, 5, 6 and 7 hours after LPS administration

    Change in axillary temperature (iAUC). A pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure.

  23. Difference in heart rate (healthy vs catabolic)

    Time frame: Measured at baseline and 1, 2, 3, 4, 5, 6 and 7 hours after LPS administration

    Change in heart rate (iAUC). A pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure.

  24. Difference in mean arterial pressure (MAP) (healthy vs catabolic)

    Time frame: Measured at baseline and 1, 2, 3, 4, 5, 6 and 7 hours after LPS administration

    Change in MAP (iAUC). A pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure.

  25. Difference in symptom score (healthy vs catabolic)

    Time frame: Measured at baseline and 1, 2, 3, 4, 5, 6 and 7 hours after LPS administration

    Change from baseline and throughout the experiment (iAUC). A pooled mean of the two catabolic days, if there is no difference between the first and second time of LPS exposure. Scale 0-5, 0=no symptoms and 5=severe symptoms

Sponsors and collaborators

Lead sponsor

University of Aarhus

Other

Collaborators

  • Aarhus University Hospital
  • Arla Foods

Registry information

Official study title

Anabolic Potential of Adding 3-hydroxybutyrate (3-OHB) to Whey Protein in a Catabolic Inflammatory Disease Model: A Human Randomized Controlled Trial

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Aug 21, 2019
Registry last updated
Jun 11, 2020

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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