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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 oxygen.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normoxia | No Intervention | Participants will sleep in room air and receive no melatonin. | |
| Hypoxia and Placebo | Placebo Comparator | 5mg placebo before sleep study |
|
| Hypoxia and Melatonin | Experimental | 5mg melatonin before sleep study |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Melatonin | Other | 5mg Melatonin |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Apnea Hypopnea Index | Measure of Sleep Apnea severity | 6 weeks |
| Neurocognitive Scores | Reflex changes between conditions | 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Loop Gain | Measurement of breathing characteristics during sleep using a flow meter attached to a CPAP mask that allows the measurement of expiratory flow | 6 weeks |
| Arousal Threshold | requirements for sleep arousal to occur |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Atul Malhotra, MD | Professor | Principal Investigator |
| Naomi L Deacon, Ph.D. | Research Associate | Study Director |
| Pamela De Young | Research Associate | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Diego | San Diego | California | 92093 | United States |
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| Label | URL |
|---|---|
| Study Website | View source |
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| ID | Term |
|---|---|
| D000860 | Hypoxia |
| D000532 | Altitude Sickness |
| ID | Term |
|---|---|
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012120 | Respiration Disorders |
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| ID | Term |
|---|---|
| D008550 | Melatonin |
| ID | Term |
|---|---|
| D014363 | Tryptamines |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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randomized, placebo controlled, double blind, cross-over trial
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| Other |
5mg Placebo capsule |
|
| 6 weeks |
| Sleep Efficiency | Time in bed divided by total sleep time | 6 weeks |
| Total Antioxidant Status | Measurement taken from blood draw | 6 weeks |
| Hypoxic Ventilatory Response | Change in breathing response while breathing low oxygen | 6 weeks |
| Hypercapnic Ventilatory Response | Change in breathing response while breathing high carbon dioxide | 6 weeks |
| D012140 | Respiratory Tract Diseases |
| D006571 | Heterocyclic Compounds |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |