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

April 23, 2019 updated by: University of Aarhus

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus, Denmark, 8000
        • Aarhus University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Casein
"LPS + 36 hour fast and bedrest" + Casein (9% leucine) - 0.6 g protein/kg bodyweight, 1/3 as bolus and 2/3 as sipping.
Dietary supplement: Casein
see experimental description
Experimental: Whey
"LPS + 36 hour fast and bedrest" + Whey (11% leucine) - 0.6 g protein/kg bodyweight, 1/3 as bolus and 2/3 as sipping
Dietary supplement: Whey
see experimental description
Experimental: Leucine-enriched whey
"LPS + 36 hour fast and bedrest" + Leucine-enriched whey (16% leucine) - 0.6 g protein/kg bodyweight, 1/3 as bolus and 2/3 as sipping
Dietary supplement: Leucine-enriched whey
see experimental description

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Change from baseline to 3.5 hours after intervention

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
Change from baseline to 3.5 hours after intervention
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
At baseline and every 30 minutes during the intervention period (3.5 hours)
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
At baseline and every 30 minutes during the intervention period (3.5 hours)
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.
Change from baseline and after 2 hours of intervention
Energy expenditure
Time Frame: At baseline and after 2.5 hours of intervention
Using indirect calorimetry for 15 min
At baseline and after 2.5 hours of intervention
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)
At baseline and after 2.5 hours of intervention
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)
Change from baseline to 3.5 hours after intervention
Changes in Glucagon concentrations
Time Frame: Change from baseline and to 1 hour and 3.5 hour after the intervention
Glucagon concentrations in blood
Change from baseline and to 1 hour and 3.5 hour after the intervention
Changes in GIP concentrations
Time Frame: Change from baseline and to 1 hour and 3.5 hour after the intervention
GIP concentrations in blood
Change from baseline and to 1 hour and 3.5 hour after the intervention
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
Change from baseline and to 1 hour and 3.5 hour after the intervention
Changes in Glucose concentrations
Time Frame: At baseline and every 30 minutes during the intervention period (3.5 hours)
Glucose concentrations in blood
At baseline and every 30 minutes during the intervention period (3.5 hours)
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)
Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
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)
Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
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)
Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
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.
Measured at baseline and 1,2,3,4,5,6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
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
Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
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
Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
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
Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)
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
Measured at baseline and 1, 2, 4, 6 and 24 hours after LPS (6-8 weeks between visit 1,2 and 3)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Aarhus

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Arla Food for Health

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Niels Moeller, Professor, Institute for clinical Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 7, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 19, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 19, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 13, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 23, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 24, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 25, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • theproteinstudy

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

We will analyse all data ourselves

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Endotoxemia

Clinical Trials on Casein

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings