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Completed

NCT Number: NCT03319550

Whey vs Casein to Combat Post-inflammatory Protein and Muscle Waste in Acute Disease

This study compares three different protein supplements (casein, whey and leucine-enriched whey) and their effect on post-inflammatory muscle waste in a model of acute disease. Each test person will undergo all three interventions.

It is believed that leucine is the primary driver of muscle protein synthesis and therefore we hypothesize that leucine-enriched whey and whey are superior to casein in combating post-inflammatory muscle waste, because of its higher leucine content (16%, 11% and 9% leucine, respectively).

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Key information

Age range

20 year–40 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Aarhus University Hospital

Aarhus, 8000, Denmark

About this study

Background:

Acute illness is accompanied by infection/inflammation, anorexia and immobilization all contributing to muscle loss, making nutritional supplement optimization an obvious target for investigation and eventually clinical intervention. In the clinical setting large heterogenicity among patients complicates investigations of muscle metabolism during acute illness. Therefore we introduce a disease model by combining "Inflammation + 36 hour fast and bedrest". Inflammation/febrile illness will be initiated by using the well-established "human endotoxemia model" with a bolus injection of Escherichia coli lipopolysaccharide (LPS), known to cause inflammation comparable with the initial phase of sepsis. The amino acid leucine has shown to be particularly anabolic in performance sports, but little is known about its potential beneficial effects during acute illness. Leucine is a powerful activator of muscle protein synthesis and it seems that protein supplements with the highest leucine content elicit a greater increase in protein synthesis than those with a smaller fraction of leucine.

The protein supplements used most in hospitals contain casein derived protein, which has a much lower leucine content than the whey protein compounds typically used in performance sports.

This study compares three different protein supplements.The study is an open, randomized crossover trial. Laboratory technicians, test subjects and investigators will be blinded.

Interventions:

I. LPS (1 ng/kg as bolus) + 36 h fasting + 36 h bedrest + Casein (9% leucine) II. LPS (1 ng/kg as bolus) + 36 h fasting + 36 h bedrest + Whey (11% leucine) III. LPS (1 ng/kg as bolus) + 36 h fasting + 36 h bedrest + Leucine-enriched whey (16% leucine)

The test objects will be given 0,6 g protein/kg, 1/3 as a bolus and 2/3 as sipping over a period of 3,5 hour. Muscle metabolism will be investigated by phenylalanine tracer using the forearm model and total protein metabolism using a carbamide tracer. Through muscle biopsies intracellular signalling pathways will be investigated.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Healthy Male
  • Age between 20-40
  • BMI between 20-30
  • Normal health examination and blood samples
  • Written informed consent

Exclusion criteria

  • Immobilisation of an extremity, unless a doctor has declared it fully rehabilitated.
  • Allergy against lidocain or latex.
  • The use of anabolic steroids
  • Disease like: Diabetes, epilepsia, infection, cardiovascular disease.

Treatment and study plan

Casein

Dietary Supplement

see experimental description

Whey

Dietary Supplement

see experimental description

Leucine-enriched whey

Dietary Supplement

see experimental description

Primary outcomes

  1. Change in muscle phenylalanine netbalance over the forearm muscle

    Time frame: Change from baseline to 3.5 hours after intervention

    Changes of muscle phenylalanine net balance (= arterio(phe conc)-venous(phe conc) x flow) from baseline to 3.5 hours after intervention using the forearm model

Secondary outcomes

  1. Change in whole body protein metabolism measured by a combination of phenylalanine- and tyrosine tracer

    Time frame: Change from baseline to 3.5 hours after intervention

    Changes in whole body protein synthesis rates (umol/kg/h), breakdown rates (umol/kg/h), phenylalanine to tyrosine conversion rates (umol/kg/h) and net balance (umol/kg/h)

  2. Blood enrichment of essential amino acids

    Time frame: At baseline and every 30 minutes during the intervention period (3.5 hours)

    measures of essential amino acids in the blood

  3. Changes in insulin concentrations

    Time frame: At baseline and every 30 minutes during the intervention period (3.5 hours)

    Measures of insulin concentration in blood

  4. Change in Intracellular signalling in muscle measured by western blotting.

    Time frame: Change from baseline and after 2 hours of intervention

    Investigating intracellular activity of muscle metabolism pathways by western blotting.

  5. Energy expenditure

    Time frame: At baseline and after 2.5 hours of intervention

    Using indirect calorimetry for 15 min

  6. Changes in Glucose, fat and protein oxidation rates

    Time frame: At baseline and after 2.5 hours of intervention

    Using indirect calorimetry for 15 min for measuring glucose- (mg/kg/min), fat- (mg/kg/min) and protein oxidation (mg/kg/min)

  7. Change in muscle breakdown and synthesis rates measured by phenylalanine tracer

    Time frame: Change from baseline to 3.5 hours after intervention

    changes from baseline to 3.5 hours after intervention in Ra(phe)=breakdown (umol/kg/h) and Rd(phe)=synthesis rate (umol/kg/h)

  8. Changes in Glucagon concentrations

    Time frame: Change from baseline and to 1 hour and 3.5 hour after the intervention

    Glucagon concentrations in blood

  9. Changes in GIP concentrations

    Time frame: Change from baseline and to 1 hour and 3.5 hour after the intervention

    GIP concentrations in blood

  10. Changes in GLP-1 concentrations

    Time frame: Change from baseline and to 1 hour and 3.5 hour after the intervention

    GLP-1 concentrations in blood

  11. Changes in Glucose concentrations

    Time frame: At baseline and every 30 minutes during the intervention period (3.5 hours)

    Glucose concentrations in blood

  12. Changes in heart rate profile upon repeated LPS exposure

    Time frame: Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)

    heart rate (beats/min)

  13. Changes in temperature profile upon repeated LPS exposure

    Time frame: Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)

    Axillary temperature (celcius)

  14. Changes in blood pressure profile upon repeated LPS exposure

    Time frame: Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)

    blood pressure (mmHg)

  15. Changes in symptom score profile upon repeated LPS exposure

    Time frame: Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)

    symptom score (from 0-5) for nausea, back pain, muscle pain, headache and chills. 0=no symptoms, 5=severe symptoms.

  16. Changes in TNfalfa profile upon repeated LPS exposure

    Time frame: Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)

    TNfalfa blood concentrations

  17. Changes in IL-1 profile upon repeated LPS exposure

    Time frame: Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)

    IL-1 blood concentrations

  18. Changes in IL-6 profile upon repeated LPS exposure

    Time frame: Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)

    IL-6 blood concentrations

  19. Changes in IL-10 profile upon repeated LPS exposure

    Time frame: Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)

    IL-10 blood concentrations

Sponsors and collaborators

Lead sponsor

University of Aarhus

Other

Collaborators

  • Arla Foods

Registry information

Official study title

Whey vs Casein to Combat Post-inflammatory Protein and Muscle Waste - Combining Endotoxemia, Immobilisation and Fasting in Healthy Young Males in a New Model of Acute Febrile Disease

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Oct 24, 2017
Registry last updated
Apr 25, 2019

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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