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

Sponsor

University of California, San Diego (Other)

Overall Status

Completed

CT.gov ID

NCT03368352

Collaborator

(none)

Enrollment

Location

Arms

17.5

Actual Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Altitude Hypoxia Ventilation Sleep Oxidative Stress Neurocognitive Dysfunction	Dietary Supplement: Melatonin Other: Hypoxia	Early Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Randomized, double-blind, placebo controlledRandomized, double-blind, placebo controlled

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Jul 4, 2017

Actual Primary Completion Date :

Dec 20, 2018

Actual Study Completion Date :

Dec 20, 2018

Arms and Interventions

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

Arm

Intervention/Treatment

No Intervention: Normoxia

Sleep in normal room air with no drug

Placebo Comparator: Hypoxia with Placebo

Sleep in hypoxic tent after taking Placebo 1 hour before bed.

Other: Hypoxia

Sleep in a hypoxic tent simulating high altitude

Experimental: Hypoxia with Melatonin

Sleep in hypoxic tent after taking 5 mg Melatonin before bed.

Dietary Supplement: Melatonin

Dietary supplement melatonin

Outcome Measures

Primary Outcome Measures

Neurocognitive function [30 minutes after arousal from sleep]
Stroop-color word test median number of errors. Higher numbers indicate worse performance.
Endothelial function [5 minutes after arousal from sleep]
Reactive hypermedia index via EndoPat
Lipid peroxidation in serum [immediately after arousal from sleep]
Concentration of Malondialdehyde in serum samples
Hypercapnic hypoxic ventilatory sensitivity [1 hour after arousal from sleep]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.