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

R

Robert L. Owens

Status

Completed

Conditions

Intermittent Hypoxia

Treatments

Other: Placebo
Other: Melatonin

Study type

Interventional

Funder types

Other

Identifiers

NCT03588676
UCSD170200

Details and patient eligibility

About

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.

Full 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.

Enrollment

39 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Triple Blind

39 participants in 3 patient groups, including a placebo group

Normoxia
No Intervention group
Description:
Participants will sleep in room air and receive no melatonin.
Hypoxia and Placebo
Placebo Comparator group
Description:
5mg placebo before sleep study
Treatment:
Other: Placebo
Hypoxia and Melatonin
Experimental group
Description:
5mg melatonin before sleep study
Treatment:
Other: Melatonin

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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