The objective of this study is to investigate whether a cycling exercise coupled with artificial gravity via a short-arm human centrifuge helps to prevent and / or reduce the deleterious effects induced by 60 days of anti-orthostatic bedrest.

The secondary objective is to investigate whether the combination of a supine cycling exercise with artificial gravity is more effective than the same supine cycling exercise alone in preventing or reducing the effects of head-down bedrest.

During a randomized, 60 day bed rest study, in 24 healthy male adults, the two following aims will be undertaken:

• Fourteen scientific protocols will assess the changes in the cardiovascular, metabolic, musculoskeletal, neuro-sensorial, haematological, and immunological systems.
• In the above-mentioned systems, the comparative potential beneficial effects of the two countermeasure protocols will also be investigated by the scientific protocols and bedrest standard measurements (BSM).

Space flights have shown the possibilities and limitations of human adaptation to space. For the last 60 years, results have shown that the space environment and microgravity in particular, cause changes that may affect the performance of astronauts. These physiological changes are now better known: prolonged exposure to weightlessness can lead to significant loss of bone and muscle mass, strength, cardiovascular and sensory-motor deconditioning, immune, hormonal and metabolic changes .

Moreover, recently a new suite of physiological adaptations and consequences of space flight has been acknowledged. Indeed, after long flights, some astronauts present persistent ophthalmologic changes, mostly a hyperopic shift, an increase in optic nerve sheath diameter and occasionally a papillary oedema now defined by National Aeronautics and Space Administration (NASA) as Spaceflight-Associated Neuro-ocular Syndrome (SANS). Some of these vision changes remain unresolved for years post-flight. This phenomenon has most likely existed since the beginning of human space flight but is just recently being recognized as a major consequence of adaptation to microgravity.

Overall, spaceflight induces physiological multi-system deconditioning which may impact astronauts' efficiency and create difficulties upon their return to normal gravity. Understanding the underlying mechanisms of these processes and developing efficient countermeasures to prevent, limit or reverse this deconditioning remain important challenges and major priorities for manned space programs.

The space agencies are actively engaged in studying the physiological adaptation to space environment through studies on board the International Space Station (ISS) but also on the ground. Indeed, considering the limited number of flight opportunities, the difficulties related to the performance of in-flight experiments (operational constraints for astronauts, limited capabilities of in-flight biomedical devices), ground-based experiments simulating the effects of weightlessness are used to better understand the mechanisms of physiological adaptation, design and validate the countermeasures.

Different methods are used to simulate microgravity on Earth. However, two approaches, -6° head-down bed rest (HDBR) and dry immersion (DI) have provided possibilities for long-term exposures with findings closest to those seen with a weightless state. They produce changes in body composition (including body fluid redistribution), cardiovascular and skeletal muscle characteristics that resemble the effects of microgravity. One of the advantages of the HDBR model is that it has now been used in a great number of studies internationally, and its effects have long been described and compared with those of microgravity and spaceflight. Long-term bedrest is the gold-standard method for studying the effects of weightlessness and to test countermeasures.

The HDBR, as the name implies, implicates a long (from several weeks to a year) stay in the supine position, the head tilted down by -6° from the horizontal plane. HDBR is the most frequently used ground-based simulation for gravitational unloading of the human body in western countries.

During human space missions, the current most effective countermeasure is physical exercise. However, it is both time-consuming and not completely satisfactory. One of the solutions for this is to combine physical exercise with artificial gravity, with the use of a short-arm human centrifuge (SAHC). This study proposes to test the effectiveness of a countermeasure protocol combining Artificial Gravity (AG) with a cycling exercise, and to compare it with only a cycling exercise, and with a complete lack of physical exercise.

Inclusion Criteria:

• Healthy male volunteer (see below the description of medical tests and laboratory analysis performed at the selection visit)
• Aged 20 to 45 years
• No overweight nor excessive thinness with BMI (weight kg/ height m2) between 20 and 27 kg/m2
• Height between 158 and 190 cm
• Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination): in particular, free from any chronic disease or any acute infectious disease or cardiovascular, neurological, of the ear, nose, throat (especially orthostatic hypotension and vestibular disorders), orthopaedic or musculoskeletal disorders
• Good mental health: tests and psychological interview will be held by a specialist in extreme environment
• Fitness level assessment: 35 mL/min/kg < VO2max < 55 mL/min/kg
• Non active smokers
• No alcohol or drug dependence, and no medical treatment
• Covered by a Health Insurance System
• Having signed the information consent
• Free of any engagement during the study

Exclusion Criteria:

• Any history or presence of clinically relevant cardiovascular, neurological or ear, nose, throat disease, any chronic disease; any acute infectious disease. Particularly:
• Symptomatic orthostatic hypotension whatever the decrease in blood pressure, or asymptomatic postural hypotension defined by a decrease in systolic blood pressure equal to or greater than 20 mmHg within 3 minutes when changing from the supine to the standing position,
• Cardiac rhythm disorders,
• Hypertension,
• Chronic back pains,
• Vertebral fracture, scoliosis, or herniated disc,
• Glaucoma,
• Self-reported hearing problems,
• Vestibular disorders
• History of migraines,
• History of hiatus hernia or gastro-esophageal reflux,
• History of thyroid dysfunction, renal stones, diabetes,
• History of head trauma,
• Abnormal result for lower limbs echo-doppler,
• History of genetic muscle and bone diseases of any kind,
• Past records of thrombophlebitis, family history of thrombosis or positive response in thrombosis screening procedure (anti thrombin III, S-protein, C-protein, factor V Leiden mutation and the mutation 20210 of the prothrombin gene),
• Bone mineral density: T-score ≤ -1.5,
• Poor tolerance to blood sampling,
• Having given whole blood (more than 7 mL/kg) in a period of 8 weeks or less before the start of the experiment, or having given whole blood more than 2 times in the past year,
• Significant history of allergy, especially no dermatological or food allergy,
• Significant anomaly detected in the biological analysis,
• Positive reaction to any of the following tests: hepatitis A immunoglobulin, hepatitis B antigen, anti hepatitis C antibodies, anti Human Immunodeficiency Virus 1+2 antibodies,
• Vegetarian or vegan,
• Refusal to give permission to contact his general practitioner,
• 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 already participating or in the exclusion period of a clinical research,
• Subject who has received more than 4500 Euros within 12 months for being a research subject,
• Subject who cannot be contacted in case of emergency,
• Subject who had the two knees injured
• MRI contraindications
• History or active claustrophobia
• Osteosynthesis material, presence of metallic implants or any other contra-indication for MRI
• Vulnerable persons according to French law (L1121-5 to L1121-8) :
• Persons deprived of their liberty by an administrative or judicial decision
• Persons under involuntary psychiatric care
• Persons admitted in a health or social establishment for purposes other than research
• Minors
• Adults subject to legal protection (subject under guardianship or trusteeship) or unable to express their consent

Participants and investigators are aware of the groups distribution