The Effects of Whole Body Unloading on Physiological Function
Condition: Muscle Atrophy; Weightlessness; Sleep Disturbance; Astronaut-Bone Demineralisation Syndrome
MeSH terms: Bone Demineralization, Pathologic; Dyssomnias; Parasomnias; Muscular Atrophy
Study type: Interventional

Summary: 
      This study is a collaboration between the Centre of Human & Aerospace Physiological Sciences
      (CHAPS) and the Sleep and Brain Plasticity Centre (Department of Neuroimaging) at King's
      College London and the Sleep Disorders Centre at Guy's Hospital.The main purpose of the study
      is to evaluate the effects of a 7 day unloading period (simulating micro gravity) on muscle
      mass using three independent methods; two scanning techniques (magnetic resonance imaging
      (MRI) and dual x-ray absorptiometry (DXA)) and one that involves swallowing a capsule that
      contains a harmless chemical called creatine (D3-Creatine (D3-cr)) and then measuring its
      concentration in urine. In order to induce muscle loss, participants will be required to lie
      flat on their back on a water bed filled with water and salt (called hyper-buoyancy flotation
      (HBF)). As this situation is similar to that experienced in space, the investigators will
      also measure the effect of HBF on sleep, brain and physiological function - all things known
      to change in astronauts. Sixteen male subjects (18-40 yrs) will be recruited to participate
      in the study that will require physiological testing before, during and following both 7 days
      of normal conditions and 7 days of HBF bed-rest. Each subject will be exposed to the same
      conditions and assessments over the study period. As some loss of muscle is expected,
      participants will be offered an exercise rehabilitation programme upon completion of HBF with
      self-monitored and/or guided sessions based on those provided by the Space Medicine Office of
      the European Space Agency to returning astronauts.
    

Detailed description: 
      The rapid loss of skeletal muscle occurs in extreme physiological conditions, most notably
      within intensive care, hypoxia and during spaceflight. The cause of this accelerated loss is
      unknown; however, interventions aiming to slow the decline may have profound effects on
      quality of life post-surgery and, in space expedition terms, the ability to complete mission
      critical tasks. In addition, the current methodologies available to measure total skeletal
      muscle mass have limitations, lack accuracy (anthropometry and Bioelectrical Impedance
      Analysis (BIA)) or are immobile and costly (dual x-ray absorptiometry (DXA) and magnetic
      resonance imaging (MRI)).

      The primary aim of this study is to investigate whole body skeletal muscle loss induced
      through 7 consecutive days of whole-body immobilisation using three independent methods; dual
      x-ray absorptiometry (DXA), magnetic resonance imaging (MRI) and D3-Creatine dilution
      (D3-cr). A number of secondary aims are also targeted, which have the shared objective to
      measure the impact of 7-days of immobilisation on HBF; 1. Muscular, neuromuscular and
      cardiovascular adaptation; 2. Neurophysiology, sleep architecture and cognition; 3. A range
      of spaceflight specific measures, aiming to characterise the intervention proposed within
      this study (hyper-buoyancy flotation (HBF) bed rest) as an alternative ground-based analogue
      to observe the physiological response to microgravity.

      The muscular, neuromuscular and cardiovascular research is performed by King's College London
      Centre of Human & Aerospace Physiological Sciences (KCL CHAPs) and ranges from measurement of
      whole-body change, to cellular adaptation. Total skeletal muscle mass will be measured using
      DXA, MRI and D3-cr as well as the cross-sectional area of a single muscle group (quadriceps)
      using ultrasound. A biopsy will be taken from the same muscle group (quadriceps) in order to
      investigate changes in muscle protein synthesis (MPS), myofibre size, force and protein: DNA
      ratio. Muscle performance will also be measured, from whole-body power output using a
      countermovement jump, to force expressed by the trunk, quadriceps, calf and handgrip. Muscle
      tone will be measured in three flexor and three extensor muscles in the calf, forearm and
      lower back. The plantarflexion muscles in the calf will be further assessed, with ankle
      proprioception, maximal strength and surface EMG of the medial gastrocnemius measured. Blood
      samples will be taken in order to distinguish changes in immunity and bone markers. The
      subject's height will be measured and intervertebral disc morphology distinguished using
      ultrasound and MRI.

      The neuromuscular and muscle performance measurements will be obtained concurrently.
      Electrical activity produced by the skeletal muscles will be recorded and evaluated using
      electromyography (EMG). Prior to the force expression of the quadriceps being tested, pads
      will also be positioned for the muscle to be electrically stimulated and for a maximal
      involuntary force to be measured. Lastly, a cycle ergometer assessment will be undertaken,
      where power is ramped gradually and maximal aerobic utilisation (VO2max) determined.

      The neurophysiology, sleep architecture and cognition investigation will be in collaboration
      with the Sleep and Brain Plasticity Centre (Department of Neuroimaging, IoPPN) and the Sleep
      Disorders Centre at Guy's Hospital. This study will look at any ensuing changes in sleep
      architecture and neurophysiology. Any associated cognitive or brain structural changes, which
      may be induced through 1 week of whole-body immobilisation, will also be investigated.

      The procedures outlined are designed to assess known physiological adaptations occurring as a
      consequence of a micro-gravity environment, and therefore prove useful comparative tools from
      which the HBF model can be evaluated.

      Sixteen male subjects (18-40 yrs) will be recruited to undertake test procedures pre- and
      post- a 7-day control period, where they will continue their habitual activities and be
      provided with their total (controlled) calorie intake, and pre- and post- a 7-day unloading
      period, where subjects will be required to remain on a hyper-buoyancy flotation (HBF) bed.
    

Intervention name(s): HBF Bed Rest
Intervention type(s): Other
Intervention description(s): 7 days of bed rest on hyper-buoyancy floatation (HBF)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic