Toulouse Male Long Term Bed Rest 2001-2002
Condition: Simulation of Weightlessness by Anti-Orthostatic Long Term Bed Rest
Study type: Interventional
Phase: Phase 1

Summary: 
      Microgravity during space flight induces physiological changes that affect astronauts' health
      and performance. Space flight simulations such as prolonged bed rest can mimic some of these
      changes and provide study conditions that are more accessible than during space flight. The
      European Space Agency, ESA together with the French national space agency, CNES and the
      Japanese national space agency, NASDA are performing extensive studies using long duration
      bed rest.

      Previous studies including several long and short term bed rest campaigns have yielded
      significant medical data on the physiological changes induced by space flight. These data can
      be used to study the effect of countermeasures, methods helping to prevent these
      physiological changes.

      The long duration bed rest, lasting 3 months undertakes a variety of investigations involving
      28 subjects. This study focuses on countermeasures, studying the effect of a bone tissue
      stabilisation medication and resistive exercises to determine their suitability for use
      during long duration stays on ISS.

      The physiological changes recorded during space flight and bed rest mimic those observed in
      some diseases and in the aging process. Significant clinical applications are expected as a
      direct result of this experiment and future equivalent studies.
    

Detailed description: 
      The spaceflights undertaken to date demonstrated that Man can adapt to the conditions
      existing in space, particularly to weightlessness. However, the space environment and the
      prevailing micro-gravity induce modifications which may affect the performances of the
      astronauts. These modifications concern in particular the cardiovascular and hormonal
      systems, the muscles, the bones, the blood and the immune system. Other problems may occur
      during long duration flights, such as the problems created by psychological stress due to the
      confinement, or those resulting from the cosmic rays (radiation).

      In view of the fact that space flight opportunities are few, experiences simulating the
      effects of weightlessness experiences are undertaken on the earth, in order to better
      understand the adaptation mechanisms, prepare the spaceflights, perfect and evaluate
      corrective methods (called counter-measures) such as physical exercise or medication, to
      facilitate the astronauts' return to base. These experiments are also a necessity, in view of
      the difficulties encountered when carrying out certain experiences during the flights, due to
      the presence of too few astronauts on board, and to the lack of advanced biomedical devices
      onboard (scanner, etc.). The most common simulation is that of the anti-orthostatic bed rest
      (tilted position with the head slightly under the feet at a -6° angle).

      Since the current objective is to simulate flights in the International Space Station (3 to 6
      months) or possible flights to Mars (500 to 1000 days), it is mandatory to extend the
      duration of the simulation experiments. This is why three Space Agencies, CNES (France),
      European Space Agency (ESA, European Union), National Space Development Agency of Japan
      (NASDA, Japan) decided to join forces and undertake in common such simulation campaigns on
      ground, to best apprehend the adaptation processes to the constraints of the space
      environment.

      The 2 main objectives of this experiment are:

        -  to study the physiological changes mechanisms during a ground-based experiment
           simulating long duration spaceflights,

        -  to develop and validate preventive methods (countermeasures) using standard tests.

      This is why we will test in the present study the effects of an orthostatic bed rest
      (decubitus) of 90 days (3 months) on the following physiological systems :

        -  the bones,

        -  the muscles,

        -  the cardiovascular system and its control mechanisms,

        -  the sleep,

        -  the spine.

      In the absence of gravity, the weight of the astronaut and that of the objects disappear
      completely. This induces modifications of the bones and the muscles which can severely affect
      the astronaut's life during the flight, and even more when returning to earth. This is a
      fundamental point to study, since it may become a limiting factor and even an obstacle to
      long duration flights. This experiment should also permit the test of physical exercise
      program and of a drug, pamidronate (AREDIA®), as counter-measures against the effects of
      weightlessness on the locomotion system (skeleton and muscles).

      A total of 28 volunteers will participate to this experiment, split into three groups. Said
      experiment will spread on 2 years, 14 volunteers participating each time. The 3 groups are
      the following:

        -  Group "physical exercise" (9 volunteers),

        -  Group "drug" (pamidronate) (9 volunteers),

        -  Group "control" (10 volunteers).

      Members of the groups will be drawn by lot among the participants

        -  Group "Exercise" : exposure of Man to microgravity results in a muscular atrophy which
           affects the muscles of the lumbar region and those of the lower limbs which are
           concerned by the standing position and the locomotion. During certain flights, physical
           exercise programs have been implemented, in order to fight against this muscular
           atrophy, maintain the physical condition required for the mission and prepare the
           astronauts for their return on earth. In the course of the present experiment, a
           physical exercise program will be tested on the 9 volunteers of this group (resistance
           training using both calf and knee extensor muscles with a special devicecalled
           Fly-Wheel).

        -  Group "Drug" : a Man in microgravity is the sole experimental model available to test
           the rapid occurrence of osteoporosis on a healthy subject. Osteoporosis, or porous bone,
           appears whenever the rate at which the bone material is replaced falls below that of
           resorption, thus creating a bone fragility and an increased risk of fracture (hip, spine
           and wrist essentially). It appears generally after menopause, when associated with aging
           and a lack of physical activity. The pamidronate (Aredia®) is a drug present on the
           market since many years, used for the treatment of several bone pathologies. This drug
           will be tested on the 9 volunteers of this group, to demonstrate its efficiency in
           treating of bone modifications. This drug (60mg) will be infused intravenously 14 days
           before bed rest.

        -  Group "control" : this group will serve as reference for the experimentation. Volunteers
           in this group will be without physical exercise and without drug. The existence of this
           group is necessary to be able to compare the results of the 2 types of counter-measures.

      The experience will be carried out during a 120 days stay (a total of 4 months) at the Space
      Clinic and will comprise:

        -  1 control ambulatory period of 15 days (subjects to report on day before) (-15 at -1),

        -  1 anti-orthostatic (-6°) bed rest period of 90 days (1 at 90),

        -  1 recovery ambulatory period of 15 days (subjects to depart the following morning) (+1
           at +15), representing a total of 122 nights spent at the clinic for all volunteers.

      The assessments will be done by different European and Japanese scientific teams,each one
      specialising in a specific domain. None of the 3 groups of volunteers will be submitted to
      all experimentation programs.
    

Intervention name(s): Ethidronate; Physical training
Intervention type(s): Drug; Behavioral
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: bedrest; spaceflight; Weightlessness; Countermeasure