Clinical trial NCT03594799: A New Nutritional Countermeasure to Prevent the Deconditioning Induced by 60 Days of Antiorthostatic Bed Rest
Official title: Effects of a Nutritional Cocktail Consisting of Anti-oxidant and Anti-inflammatory Supplements to Prevent the Deconditioning Induced by 60 Days of Antiorthostatic Bed Rest
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Weightlessness
Weightlessness; Adverse Effect
Keywords: Simulated Microgravity
Weightlessness
Countermeasure
Bedrest
Lead sponsor: Centre National d'Etudes Spatiales
Sponsor class: OTHER_GOV
Collaborators: name: European Space Agency
First posted: 2018-07-20
Enrollment: 20
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The objective of this study is to investigate whether the cocktail of natural antioxidants XXS-2A-BR2 comprising vitamin E and coupled with omega-3 helps to prevent and / or reduce the deleterious effects induced by long term physical inactivity through antiorthostatic bedrest. During a randomized 60 day bed rest study in 20 healthy male adults the two following aims will be undertaken:

* Sixteen scientific protocols will assess the changes in the cardiovascular, metabolism, muscle, bone, neuro sensorial, hematological and immunology systems.
* In the above mentioned systems, the potential beneficial effects of the countermeasure protocol will also be investigated.

Detailed description: Space flights have shown the possibilities and limitations of human adaptation to space. For the last 50 years, results showed that the space environment and microgravity in particular, cause changes that may affect the performance of astronauts. These physiological changes particularly challenge the cardiovascular, metabolic, muscle and bone functions. Space agencies regularly conduct simulations on the ground on healthy volunteers to mimic the effects of weightlessness (head down bed rest model) to better understand the mechanisms of adaptations of the organism to space, and develop ways to prevent and / or reduce the negative biological effects of microgravity on astronauts. These protocols are called countermeasures. Since the beginning of space missions, various countermeasures have been tested on the ground and in-flight, including different exercise protocols. To date, however, none has been entirely satisfactory and space agencies continue to conduct simulation studies to evaluate new countermeasures. Nowadays, the human spaceflight program has entered the next phase of space exploration towards the Moon and Mars and there are clearly inherent medical challenges with such a goal, among which, countermeasure developments are a clear priority.

Based on recent evidences, the next countermeasure to be tested during a 60-day bed rest includes a nutritional countermeasure composed of an anti-oxidant and anti-inflammatory dietary mix.

Eligibility criteria: Inclusion Criteria:

* Healthy male volunteer (see below the description of medical tests and laboratory analysis performed at the selection visit),
* Age 20 to 45,
* No overweight nor excessive thinness with BMI (weight Kg/ height m2) between 22 and 27,
* Height between 158 and 190 cm,
* No personal nor family past record of chronic or acute disease or psychological disturbances which could affect the physiological data and/or create a risk for the subject during the experiment,
* Fitness level assessment:

  * if age \< 35 years: 35 ml/min./kg \< VO2max \< 60ml/min./kg,
  * if age \> 35 years: 30 ml/min./kg \< VO2max \< 60ml/min./kg
* Active and free from any orthopedic, musculoskeletal and cardiovascular disorders,
* Non smokers,
* No alcohol, no drug dependence and no medical treatment,
* No shift work or travel across more than one time zone in previous 2 months,
* Covered by a Social Security system,
* Have signed the information consent,
* Free of any engagement during the three hospitalization planned periods.

Exclusion Criteria:

* - Past record of orthostatic intolerance,
* Cardiac rhythm disorders,
* Chronic back pains,
* History of hiatus hernia or gastro-esophageal reflux,
* History of thyroid dysfunction, renal stones, diabetes, migraines,
* Past records of thrombophlebitis, family history of thrombosis or positive response in thrombosis screening procedure,
* Allergy including xylocaine allergy
* Abnormal result for lower limbs echo-doppler,
* History or active claustrophobia,
* History of genetic muscle and bone diseases of any kind,
* History of sleep disorders, no shift work or travel across more than one time zone in previous two months
* Vestibular disorders,
* Audition problem,
* Vision corrected no more than 20/30, color-blindness
* Bone mineral density: T-score ≤ -1.5,
* Osteosynthesis material, presence of metallic implants,
* History of knee problems or joint surgery/broken leg
* Poor tolerance to blood sampling,
* Having given blood (more than 8ml/kg) in a period of 8 weeks or less before the start of the experiment,
* Special food diet, vegetarian or vegan, food allergy especially allergic to peanut or soya.
* Positive reaction to any of the following tests: HVA IgM (hepatitis A), HBs antigen (hepatitis B), anti-HVC antibodies (hepatitis C), anti-HIV1+2 antibodies,
* Subject already participating or in the exclusion period of a clinical research,
* Refusal to give permission to contact his general practitioner,
* Incarcerated persons,
* Subject who, in the judgment of the investigator, is likely to be non-compliant during the study, or unable to cooperate because of a language problem or poor mental development,
* Subject who has received more than 4500 Euros within 12 months for being a research subject.
* Subject under guardianship or trusteeship.

Primary outcomes:
measure: Change in fasting plasma triglycerides concentration
timeFrame: 60 days
Secondary outcomes:
measure: Change in vertebral bone marrow fat fraction.
timeFrame: 60 days
measure: Change in B lymphopoiesis
timeFrame: 60 days
measure: Changes in myokines.
timeFrame: 60 days
measure: Change in cardio-postural stability
timeFrame: 60 days
measure: Change in insulin sensitivity
timeFrame: 60 days
measure: Changes in brain structure
timeFrame: 60 days
measure: Change in head movements in response to a virtual projectile
timeFrame: 60 days
measure: Change in pulse wave velocity in carotid and femoral arteries
timeFrame: 60 days
measure: Adipose Tissue Transcriptomics
timeFrame: 60 days (pre and post bed rest)
measure: Measurement of changes to the sleep electroencephalogram (EEG)
timeFrame: 60 days
measure: Measurement of changes in subjective sleep quality
timeFrame: 60 days
measure: Measurement of changes in circadian rhythms of melatonin and cortisol
timeFrame: 60 days
measure: Measurement of changes in the whole-blood transcriptome in response to 60-day head down tilt bed rest
timeFrame: 60 days
measure: Change in levels of S-nitrosylated proteins
timeFrame: 60 days
measure: Change in skeletal muscle gene expression (transcriptome)
timeFrame: 60 days
measure: Change in bone resorption marker CTX
timeFrame: 60 days
measure: Change in de novo lipogenesis
timeFrame: 60 days
measure: Accuracy and precision of vestibular-evoked sway responses
timeFrame: 60 days
measure: Change in T wave morphology
timeFrame: 60 days
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Medes-Imps
Study officials:
affiliation: MEDES - IMPS
name: Arnaud BECK, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Trim WV, Walhin JP, Koumanov F, Bouloumie A, Lindsay MA, Travers RL, Turner JE, Thompson D. The Impact of Long-term Physical Inactivity on Adipose Tissue Immunometabolism. J Clin Endocrinol Metab. 2022 Jan 1;107(1):177-191. doi: 10.1210/clinem/dgab647.
citation: Austermann K, Baecker N, Zwart SR, Fimmers R, Frippiat JP, Stehle P, Smith SM, Heer M. Antioxidant Supplementation Does Not Affect Bone Turnover Markers During 60 Days of 6 degrees Head-Down Tilt Bed Rest: Results from an Exploratory Randomized Controlled Trial. J Nutr. 2021 Jun 1;151(6):1527-1538. doi: 10.1093/jn/nxab036.
citation: Liu T, Melkus G, Ramsay T, Sheikh A, Laneuville O, Trudel G. Bone Marrow Reconversion With Reambulation: A Prospective Clinical Trial. Invest Radiol. 2021 Apr 1;56(4):215-223. doi: 10.1097/RLI.0000000000000730.