Countermeasures for Visual Impairment in Astronauts
Condition: Space Flight Associated Neuro-ocular Syndrome
MeSH terms: Vision Disorders; Vision, Low
Study type: Interventional

Summary: 
      This study is being done to prevent changes in the vision of astronauts during prolonged
      residence on the International Space Station or a mission to Mars. This project will provide
      data about the efficacy of lower body negative pressure to mimic daily upright posture by
      intermittently lowering central venous pressure while in simulated microgravity (3 days of
      bed rest). The investigators expect that 3 days of bed rest will increase choroid thickness,
      and choroid area. The investigators hypothesize that nightly LBNP (-20mmHg) will prevent
      these changes.
    

Detailed description: 
      The visual impairment observed in many astronauts after long duration spaceflight aboard the
      International Space Station is considered the most important mission-threatening medical
      problem identified in the last decade of the space program. Between 2012 and 2014, NASA and
      NSBRI have spent $3-4 million/year investigating the clinical course and underlying
      mechanisms of this condition, termed the Visual Impairment Intracranial Pressure Syndrome
      (VIIP) because of its theoretical association with elevated intracranial pressure and central
      venous pressure. During the previous funding cycle, the investigators for this application
      performed the first invasive measures of intracranial pressure during acute (head down tilt
      bedrest and parabolic flight) and chronic (24 hours HDT bedrest) changes in gravitational
      gradients simulating spaceflight in healthy humans. Novel observations made from those
      studies determined that 1) there is a large range of central venous pressure experienced
      normally during changes in posture in daily life; 2) these changes occur within seconds of
      postural transients from upright to supine and then are stable over time in that position; 3)
      with acute assumption of simulated microgravity (HDT bedrest), intracranial pressure and
      central venous pressure goes up slightly from the supine position, but over the next 24
      hours, returns toward, and sometimes below the supine value because of spatial compensation
      within the brain; 4) during true microgravity (parabolic flight), the acute reduction in
      central venous pressure reduces cerebral outflow resistance and ICP decreases compared to the
      supine position, though remains above the upright position in 1G.

      The current hypothesis is that the VIIP syndrome is Not due to a pathologically elevated
      central venous or intracranial pressure. However, because there is not the usual reduction in
      pressure typically seen in the upright position on earth, the incessant, low level elevation
      in ICP (i.e., greater than upright, but less than supine) leads to adaptive changes in the
      eye which ultimately result in globe flattening, choroidal folds, and visual impairment.
      Preliminary data suggest that the use of lower body negative pressure (LBNP) can lower ICP
      while in the head down position, towards the values observed upright. The investigators
      propose that applying LBNP during sleep in space would be a practical strategy to restore a
      relevant (though reversed) circadian variability in central venous pressure that would then
      prevent adaptive changes in the eye. The investigators propose the following hypothesis:

      Hypothesis 1: Repeated administration of LBNP at night will cause a safe, sustained reduction
      in central venous pressure while asleep. This restoration of effective circadian variability
      in central venous pressure will prevent structural changes in the eye induced by
      microgravity. To test this hypothesis, the long-term efficacy of nightly LBNP (6-8 hrs) to
      simulate the upright position and prevent structural changes in the eye during four days of
      bedrest. Comprehensive, non-invasive state-of-the-art imaging will be used to examine the
      structure of the visual apparatus, using optical coherence tomography combined with invasive
      direct measurement of CVP.
    

Intervention name(s): Lower body negative pressure
Intervention type(s): Other
Intervention description(s): lower body negative pressure at -20mmHg delivered via a custom designed sleeping sack
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science