Effects of Melatonin on Sleep, Ventilatory Control and Cognition at Altitude
Condition: Intermittent Hypoxia
MeSH terms: Hypoxia
Study type: Interventional

Summary: 
      Low oxygen at altitude causes pauses in breathing during sleep, called central sleep apnea.
      Central sleep apnea causes repeated awakenings and poor sleep. Low oxygen itself and the
      induced oxidative stress can damage mental function which is likely worsened by poor sleep.
      Reduced mental function due to low oxygen can pose a serious danger to mountain climbers.
      However there is also mounting evidence that even in populations of people that live at high
      altitudes and are considered adapted, low oxygen contributes to reductions in learning and
      memory. Therefore there is a serious need for treatments which may improve sleep, control of
      breathing and mental function during low oxygen.Therefore this study aims to determine how
      melatonin effects control of breathing, sleep and mental performance during exposure to low
      oxygen.
    

Detailed description: 
      Research has shown that exposure to low oxygen at altitude causes neurocognitive impairment
      (impaired mental processing, memory, attention, learning, etc). This impairment in cognitive
      performance poses a serious risk to mountain climbers and while it has traditionally been
      thought that people who live at high altitude have adapted to it, evidence shows there is
      still considerable damage to the brain and impairments in cognitive function of people who
      live and work at high altitude.

      As every cell in the body requires oxygen to survive and function, impairment in cognitive
      performance at altitude is thought mainly due to reduced oxygen availability to the central
      nervous system. However, low oxygen at altitude also causes unstable breathing during sleep
      which results in short periods where the brain stops sending the signal to breath, called
      central sleep apnea (CSA). During apneas (pauses in breathing) blood oxygen drops even lower
      and people typically wake up briefly and hyperventilate after apneas. Therefore at altitude
      people usually get less sleep, their sleep is broken with periods of wakefulness during the
      night and they experience repeated bouts of severe low blood oxygen levels. Sleep plays a
      critical role in how the brain repairs and also converts newly acquired information into
      long-term memory. Therefore broken and reduced sleep can impair cognitive performance, memory
      and learning. Repeated bouts of severe low oxygen also produces highly reactive molecules
      that cause damage to cells, called oxidative stress. Oxidative stress also prevents the brain
      from forming long-term memories and in severe cases (such as extremely high altitude and long
      duration exposure) can cause neurons in the brain to die. Therefore although sustained low
      oxygen at altitude likely impairs cognitive function, disturbed sleep and repeated bouts of
      severely low oxygen likely also contribute to causing brain damage and impaired cognitive
      performance.

      Melatonin is a hormone produced in the pineal gland of the brain during the night which
      signals to the brain that it is time to sleep. Melatonin is also a very powerful antioxidant
      which naturally helps to prevent damage in the body from oxidative stress. A study previously
      reported that melatonin taken 90 mins before bed at 4,300 m (14,200 ft) reduced the time
      taken to fall asleep, it reduced the number of times people woke up during sleep and improved
      cognitive performance the following day. However how melatonin caused these effects was not
      determined. Therefore this study aims to determine how melatonin affects ventilatory control,
      sleep and neurocognitive performance during sustained hypoxia.
    

Intervention name(s): Melatonin; Placebo
Intervention type(s): Other; Other
Intervention description(s): 5mg Melatonin; 5mg Placebo capsule
Intervention MeSH terms: Melatonin
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: randomized, placebo controlled, double blind, cross-over trial
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Hypoxia; High Altitude; Melatonin; Neurocognitive