Clinical trial NCT01655979: Medium-term Bedrest Whey Protein (MEP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Countermeasure Evaluation
Lead sponsor: DLR German Aerospace Center
Sponsor class: OTHER
Collaborators: name: European Space Agency
name: University Hospital, Clermont-Ferrand
name: Institut Pluridisciplinaire Hubert Curien, Strasbourg, France
name: Charite University, Berlin, Germany
name: University of Milan
name: Université de Nice Sophia Antipolis
name: University of Ottawa
name: Manchester Metropolitan University
name: University of Toronto
name: Medical University of Graz
name: University of Cologne
name: Radboud University Medical Center
name: University Hospital, Lille
name: Leiden University Medical Center
First posted: 2012-08-02
Enrollment: 10
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The human being has shown that he can live and work in the space environment, but due to the lack of essential mechanical load on muscle and bone, the fluid-shift as well as alterations in the acid-base balance (mainly on account of nutritional factors), the exposure to microgravity results in a gradual degradation of muscle, bone and cartilage, deconditioning of the cardiovascular system and metabolic changes. Countermeasures to prevent all the deconditioning of the physiological systems are not yet fully effective and require further investigation.

A commonly utilized model of simulating the physiological effects of microgravity on the human organism on ground is the 6° head-down-tilt bed rest. In the present study the model has been used to study potential countermeasures to spaceflight-associated deconditioning.

One of the most constrictive changes appearing during space flight as well as during bed rest, are disuse-induced muscle losses. These are associated with a decrease in muscle protein synthesis, rather then an increase in muscle protein breakdown. Besides an effective training countermeasure, nutritional countermeasures gain respect in this context: supplementing conventional diets with whey protein or essential amino acids has been shown to increase muscle protein synthesis. Due to these anabolic properties whey protein seems promising to counteract disuse-induced muscle wasting.

Drawbacks of a high protein intake are calciuric effects, ascribed to the proton-release when metabolizing sulfur-containing amino acids. The so called 'low grade metabolic acidosis' has also shown to activate osteoclastic bone resorption and muscle protein degradation. Therefore, to maximize the anabolic potential of a whey protein supplementation, the acidogenic properties need to be compensated. As previous works suggest, a shift of acid base balance into the acid direction and the resulting changes in bone and protein turnover may be hindered by supplementing alkaline mineral salts.

In this regard, a mid-term bed rest study was performed in order to investigate the effect of a combined whey protein (0.6 g/kg body weight/day) and potassium bicarbonate (90 mmol/day) supplementation as a potential countermeasure to multiple physiological and metabolic alterations on the human body resulting from real and simulated microgravity.


Eligibility criteria: Inclusion Criteria:

* Healthy males, 20 -45 years
* BMI: 20 - 25 kg/m2
* Height: 158 - 190 cm
* Weight: 65 - 85 kg
* maximum relative oxygen uptake: 30 - 60 ml/min/kg
* non-smokers
* successful medical and psychological screening
* Willingness to participate in the entire study
* signed informed consent
* social insurance
* Clear criminal background check

Exclusion Criteria:

* Abuse of drugs, medicine or alcohol
* Vegetarians, Vegans
* Migraines
* History of mental illness
* Claustrophobia
* History of: thyroid dysfunction, renal stones, diabetes, allergies, hypertension, hypocalcaemia, uric acidaemia, lipidaemia, hyperhomocysteinaemia
* Rheumatism
* Muscle-, Cartilage- or Joint Injuries
* Gastro-esophageal reflux disease, renal function disorder, Hiatus hernia
* Chronic back pain
* Bone diseases
* Herniated discs
* Achilles tendon injuries
* Cruciate ligament rupture or any other severe knee injury
* BMD more than 1.5 SD \< t-score
* History of orthostatic intolerance or vestibular disorders
* Anaemia
* Vitamin D Deficiency
* Positive response in thrombosis screening
* Use of metallic implants, osteosynthesis material
* Porphyria, Blood dyscrasia
* HIV, Hepatitis
* Increased Inner Eye pressure
* Intolerance to local anesthetics
* Participation in another study up to three month before study onset

Primary outcomes:
measure: Change in body composition
timeFrame: Baseline, after 21 days of bed rest
Secondary outcomes:
measure: Plasma Volume
timeFrame: Baseline, after 21 days of bed rest
measure: Maximum volume of oxygen uptake
timeFrame: Baseline, after 21 days of bed rest
measure: Isometric torque
timeFrame: Baseline, after 21 days of bed rest
measure: Muscle fatigue
timeFrame: Baseline, after 21 days of bed rest
measure: Bone metabolism
timeFrame: Baseline, after 2,5,14,21 days of bed rest, 1, 5, 14, 28 days after finishing bed rest
measure: Bone mineral density + content
timeFrame: Baseline, after 21 days of bed rest
measure: Standing balance
timeFrame: Baseline, after 21 days of bed rest
measure: Locomotion
timeFrame: Baseline, after 21 days of bed rest
measure: Body mass
timeFrame: Daily for a duration of 35 days
measure: Intracranial pressure
timeFrame: Baseline, after 1,4, 7,10,13,14,15,16,17,18,19,20,21 days of bed rest,1,2,4 days after finishing bed rest
measure: Monitoring of Vitamin K status
timeFrame: Baseline, after 2,5,14,21 days of bed rest, 1, 5 days after finishing bed rest
measure: Fat metabolism
timeFrame: Baseline, after 21 days of bed rest
measure: Glucose metabolism
timeFrame: Baseline, after 21 days of bed rest, 4 days after finishing bed rest
measure: Nitrogen balance
timeFrame: Daily for a duration of 33 days
measure: Energy metabolism
timeFrame: Baseline, after 21 days of bed rest
measure: Glucocorticoid activity
timeFrame: Baseline, after 2,3,7,8,12,13,16,17 days of bed rest, 2,3 days after finishing bed rest
measure: Muscle metabolism
timeFrame: Baseline, after 21 days of bed rest
measure: Acid base balance
timeFrame: Baseline, after 2, 14, 21 days of bed rest, 5 days after finishing bed rest
measure: Sympathetic activity during orthostatic stress
timeFrame: Baseline, after 21 days of bed rest
measure: Visual Orientation
timeFrame: Baseline, after 6,12,20 days of bed rest, 2,4 days after finishing bed rest
measure: Plasma galanin and adrenomedullin responses during head up tilt test (orthostatic stress)
timeFrame: Baseline, after 21 days of bed rest
measure: Cartilage metabolism and -thickness
timeFrame: Baseline, after 2,3,5,7,14,21 days of bed rest, 5 days after finishing bed rest
measure: Hematopoetic system
timeFrame: Baseline, after 10, 21 days of bed rest, 1, 28 days after finishing bed rest
measure: Fat accumulation in bone marrow
timeFrame: Baseline, after 10, 21 days of bed rest, 3, 28 days after finishing bed rest
measure: Achilles tendon structure
timeFrame: Baseline, after 21 days of bed rest, 2, 28 days after finishing bed rest
measure: Headache - frequency and quality
timeFrame: Baseline, daily during 21 days of bed rest
measure: Muscle volume
timeFrame: Baseline, after 20, 21 days of bed rest, 3 days after finishing bed rest
measure: Free water and fat content in muscle
timeFrame: Baseline, after 20, 21 days of bed rest, 3 days after finishing bed rest
measure: Orthostatic tolerance
timeFrame: Baseline, after 21 days of bed rest
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: DLR German Aerospace Center
Study officials:
References:
citation: Rudwill F, O'Gorman D, Lefai E, Chery I, Zahariev A, Normand S, Pagano AF, Chopard A, Damiot A, Laurens C, Hodson L, Canet-Soulas E, Heer M, Meuthen PF, Buehlmeier J, Baecker N, Meiller L, Gauquelin-Koch G, Blanc S, Simon C, Bergouignan A. Metabolic Inflexibility Is an Early Marker of Bed-Rest-Induced Glucose Intolerance Even When Fat Mass Is Stable. J Clin Endocrinol Metab. 2018 May 1;103(5):1910-1920. doi: 10.1210/jc.2017-02267.