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

Study Overview
=================
Brief 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. Melatonin is a hormone produced in the brain during the night which regulates sleep patterns with strong antioxidant and anti-inflammatory properties. A study previously reported that melatonin taken 90 mins before bed at 4,300 m (14,200 ft) induced sleep earlier, reduced awakenings and improved mental performance the following day. However how melatonin caused these effects was not determined. Therefore this study aims to determine how melatonin effects control of breathing, sleep and mental performance during exposure to low oxygen.

Official Title
-----------------
Effects of Melatonin on Sleep, Ventilatory Control and Cognition at Altitude.

Conditions
-----------------
Altitude Hypoxia, Ventilation, Sleep, Oxidative Stress, Neurocognitive Dysfunction

Intervention / Treatment
-----------------
* Dietary Supplement: Melatonin
* Other: Hypoxia


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Exclusion Criteria: Sleep disorders Pregnant females Smokers (quit ≥ 1 year ago acceptable) Any known cardiac (apart from treated hypertension with acceptable drugs, see below), pulmonary (including asthma), renal, neurologic (including epilepsy), neuromuscular, hepatic disease, or patients with diabetes. Prior or current use of melatonin. Use of any medications that may affect sleep or breathing, blood-thinning medications (anticoagulants), antioxidants, anti-inflammatories, medications that suppress the immune system (immunosuppressants), diabetes medications and birth control pills. A psychiatric disorder, other than mild depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders. Substantial alcohol (>3oz/day) or use of illicit drugs. Previous occurrence of high altitude pulmonary or cerebral edema. Recent exposure to altitude (>8000ft) in the last month or having slept at an altitude >6000ft in the last month. Inability to provide written informed consent or able to complete the experiment. Non-English speakers (necessary to complete neurocognitive testing). More than 10 cups of beverages with caffeine (coffee, tea, soda/pop) per day.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, double-blind, placebo controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Normoxia<br>Sleep in normal room air with no drug | |
| Placebo Comparator: Hypoxia with Placebo<br>Sleep in hypoxic tent after taking Placebo 1 hour before bed. | Other: Hypoxia<br>* Sleep in a hypoxic tent simulating high altitude<br>|
| Experimental: Hypoxia with Melatonin<br>Sleep in hypoxic tent after taking 5 mg Melatonin before bed. | Dietary Supplement: Melatonin<br>* Dietary supplement melatonin<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive function | Stroop-color word test median number of errors. Higher numbers indicate worse performance. | 30 minutes after arousal from sleep | 
| Endothelial function | Reactive hypermedia index via EndoPat | 5 minutes after arousal from sleep | 
| Lipid peroxidation in serum | Concentration of Malondialdehyde in serum samples | immediately after arousal from sleep | 
| Hypercapnic hypoxic ventilatory sensitivity | This is the one outcome. It is the gain of the ventilatory response to changes in CO2, during sustained hypoxia. Delta minute ventilation / delta mmHg CO2 during sustained hypoxia | 1 hour after arousal from sleep | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Melatonin, Altitude, Sleep, Ventilation, Cognition