Effects of Melatonin on Sleep, Ventilatory Control and Cognition at Altitude

Age Range:18 - 65
Start Date:January 10, 2018
End Date:December 30, 2021
Contact:Naomi L Deacon, Ph.D.
Phone:(619) 471-9484

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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

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

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.

Inclusion Criteria:

- Healthy Males and Females

- Age:18-65 years

Exclusion Criteria:

- Sleep Disorders

- Pregnant Females

- Smokers (quit ≥ 1 year ago acceptable)

- Cardiovascular, Pulmonary, Renal, Neurologic, Neuromuscular, or Hepatic Issues

- Diabetes

- Psychiatric disorder, other than mild depression

- Recent exposure to altitude (>8000ft) in the last month or having slept at an altitude
>6000ft in the last month
We found this trial at
San Diego, California 92093
Principal Investigator: Atul Malhotra, MD
Phone: 619-471-9484
San Diego, CA
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