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OpenTrials
Completed

NCT Number: NCT03588676

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

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.

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of California, San Diego

San Diego, California, 92093, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Melatonin

Other

5mg Melatonin

Placebo

Other

5mg Placebo capsule

Primary outcomes

  1. Change in Apnea Hypopnea Index

    Time frame: 6 weeks

    Measure of Sleep Apnea severity

  2. Neurocognitive Scores

    Time frame: 6 weeks

    Reflex changes between conditions

Secondary outcomes

  1. Loop Gain

    Time frame: 6 weeks

    Measurement of breathing characteristics during sleep using a flow meter attached to a CPAP mask that allows the measurement of expiratory flow

  2. Arousal Threshold

    Time frame: 6 weeks

    requirements for sleep arousal to occur

  3. Sleep Efficiency

    Time frame: 6 weeks

    Time in bed divided by total sleep time

  4. Total Antioxidant Status

    Time frame: 6 weeks

    Measurement taken from blood draw

  5. Hypoxic Ventilatory Response

    Time frame: 6 weeks

    Change in breathing response while breathing low oxygen

  6. Hypercapnic Ventilatory Response

    Time frame: 6 weeks

    Change in breathing response while breathing high carbon dioxide

Sponsors and collaborators

Lead sponsor

Robert L. Owens

Other

Registry information

Important dates

Study start
2018
Primary completion
2018
Study completion
2018
First posted
Jul 17, 2018
Registry last updated
Aug 14, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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