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. 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.

Study Overview

• Status: Completed
• Conditions: Sleep; Ventilation; Oxidative Stress; Neurocognitive Dysfunction; Altitude Hypoxia
• Intervention / Treatment: Other: Hypoxia; Dietary supplement: Melatonin

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • UCSD Sleep Lab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / 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

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

Collaborators and Investigators

• Sponsor: University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2017
• Primary Completion (Actual): December 20, 2018
• Study Completion (Actual): December 20, 2018

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (Actual): December 11, 2017

Study Record Updates

• Last Update Posted (Actual): January 31, 2019
• Last Update Submitted That Met QC Criteria: January 29, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Melatonin; Sleep; Cognition; Ventilation; Altitude
• Additional Relevant MeSH Terms: Mental Disorders; Respiratory Tract Diseases; Respiration Disorders; Neurocognitive Disorders; Signs and Symptoms, Respiratory; Cognition Disorders; Altitude Sickness; Cognitive Dysfunction; Hypoxia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 170200

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No