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

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ClinicalTrials.gov Identifier: NCT03588676
Recruitment Status : Recruiting
First Posted : July 17, 2018
Last Update Posted : July 17, 2018
Sponsor:
Information provided by (Responsible Party):
Robert L. Owens, University of California, San Diego

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.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
Intermittent Hypoxia Other: Melatonin Other: Placebo Not Applicable

Detailed Description:

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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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: randomized, placebo controlled, double blind, cross-over trial
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Melatonin on Sleep, Ventilatory Control and Cognition at Altitude
Actual Study Start Date : January 10, 2018
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Melatonin

Arm Intervention/treatment
No Intervention: Normoxia
Participants will sleep in room air and receive no melatonin.
Placebo Comparator: Hypoxia and Placebo
5mg placebo before sleep study
Other: Placebo
5mg Placebo capsule

Experimental: Hypoxia and Melatonin
5mg melatonin before sleep study
Other: Melatonin
5mg Melatonin




Primary Outcome Measures :
  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 Outcome Measures :
  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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03588676


Contacts
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Contact: Naomi L Deacon, Ph.D. (619) 471-9484 ndeacon@ucsd.edu
Contact: Pamela De Young (858) 246-2183 pdeyoung@ucsd.edu

Locations
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United States, California
University of California, San Diego Recruiting
San Diego, California, United States, 92093
Contact: Naomi Deacon, Ph.D.    619-471-9484    ndeacon@ucsd.edu   
Contact: Pamela De Young    (858) 246-2154    sleepresearch@ucsd.edu   
Principal Investigator: Atul Malhotra, MD         
Sub-Investigator: Naomi Deacon, Ph.D.         
Sponsors and Collaborators
Robert L. Owens
Investigators
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Principal Investigator: Atul Malhotra, MD Professor
Study Director: Naomi L Deacon, Ph.D. Research Associate
Study Chair: Pamela De Young Research Associate

Additional Information:
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Responsible Party: Robert L. Owens, Associate Physician, University of California, San Diego
ClinicalTrials.gov Identifier: NCT03588676     History of Changes
Other Study ID Numbers: UCSD170200
First Posted: July 17, 2018    Key Record Dates
Last Update Posted: July 17, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Robert L. Owens, University of California, San Diego:
Hypoxia
High Altitude
Melatonin
Neurocognitive

Additional relevant MeSH terms:
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Hypoxia
Signs and Symptoms, Respiratory
Signs and Symptoms
Melatonin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants