Effects of Naltrexone on Nocturnal Breathing Patterns at Altitude

Sleep Apnea, Central Clinical Trial

Official title:

Effects of Naltrexone on Nocturnal Breathing Patterns at Altitude

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05037032
• Other study ID #: 1392
• Status: Completed
• Phase: Phase 4
• Start date: August 8, 2021
• Est. completion date: October 17, 2021

Study information

• Verified date: April 2023
• Source: VA Loma Linda Health Care System
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sleep at altitude is often poor. The purpose of this study is to evaluate the effects of a single dose of the opioid antagonist, naltrexone, on sleep quality and periodic breathing after rapid ascent to ~3800m altitude.

Description:

Sleep at high altitude is notoriously poor due to a combination of the unusual sleep environment and hypoxia during sleep. Many people develop what is called periodic breathing (PB) during sleep. PB may improve overall mean nocturnal oxygen saturation (SpO2) although this is not entirely clear. Simultaneously, PB may further disturb sleep at altitude and has been associated with nighttime arousals from sleep. Medications that may decrease the amount of PB might improve sleep quality. The FDA approved drug, naltrexone, is a specific antagonist to the brain opioid receptors. It is a non-addicting drug which has never been studied at altitude.

Clinical Relationships: Sleep disordered breathing is a very common disorder throughout the population, but it worsens with increasing age and BMI. At the same time, many in our Veteran population live in the local mountains and undoubtedly develop PB during sleep in addition to having obstructive sleep apnea.

Objectives: The purpose to this study is to evaluate the effects of a single dose of naltrexone on PB and oxygen saturation during sleep at altitude in healthy young participants. The additional purpose will be to assess the subject-perceived sleep quality after the use of naltrexone vs. placebo.

Research Design: A prospective, randomized, double-blind, crossover study.

Methodology: We plan recruit up to 30 healthy study subjects with no history of sleep disordered breathing. Potential participants will be screened to ensure inclusion and exclusion criteria are met. A baseline low altitude sleep study will be preformed at home. No medication will be given before this baseline sleep study. The sleep study will be similar to the home sleep studies routinely used by the VA Loma Linda Healthcare System's Sleep Center. Participants will be transported for High Altitude Trip 1 to the Barcroft Laboratory at the White Mountain Research Center (WMRC) at 3810 m altitude. At WMRC they will have a sleep study performed, similar to the baseline sleep study, after taking either a single dose of naltrexone or matching placebo. After an appropriate washout period (at least 5 half-lives) subjects will again be studied (High Altitude Trip 2) taking the alternate medication (naltrexone/placebo) to the one used in the first study. Order of placebo vs. naltrexone will be randomized. Prior to sleep the subject will fill out questionnaires detailing how sleepy they are. On the morning following each sleep study, subjects will fill out a short questionnaire assessing the quality of their sleep.

Impact/Significance: Improved knowledge of the mechanisms of PB in hypoxic environments will provide important insights into diagnostic and therapeutic decisions for Veterans who suffer from sleep disordered breathing.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: October 17, 2021
• Est. primary completion date: October 17, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

1. Healthy males or females

2. Age 18 to 35 years of age

3. Body-mass index (BMI) = 27

4. At least two weeks after full vaccination for Sars-CoV-2. Proof of vaccination will be determined by the investigators.

Exclusion Criteria:

1. Current smoker or significant past smoking history (= 10 pack-years)

2. History of COPD, interstitial lung disease or other pulmonary disease that in the opinion of the investigators would compromise the subject's safety at altitude

3. History of obstructive sleep apnea, or other history of sleep disordered breathing, or previous use of nighttime continuous positive airway pressure (CPAP)

4. Any history of chronic opioid use or prior abuse history

5. Any history of alcohol abuse

6. Use of any opioid substance (prescribed or otherwise) within 2-weeks of study enrollment

7. Any medications that might, in the opinion of the investigators, interfere with or alter respiratory control, (e.g. acetazolamide). Use of oral contraceptive medications would be allowed as long as the study subject is on the same agent/dose during both arms of the study.

8. Recent (within 3 weeks) exposure to altitudes = 3,500 m at time of 1st altitude trip

Related Conditions & MeSH terms

• Altitude
• Sleep Apnea, Central

Intervention

Drug:
• Naltrexone Pill
50 mg PO one-time only
• Placebo
Matching placebo for naltrexone

Locations

Country	Name	City	State
United States	VA Loma Linda Healthcare System	Loma Linda	California

Sponsors (1)

Lead Sponsor	Collaborator
VA Loma Linda Health Care System

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nighttime oxygen saturation	Change from baseline in nighttime SpO2	Up to 60 days
Primary	Periodic Breathing	Change from baseline in portion of night spent with periodic breathing	Up to 60 days
Primary	Epworth Sleepiness Scale	Subjective measurement of one's daytime sleepiness (0 = less sleepy, 24= excessively sleepy)	Up to 60 days
Primary	Stanford Sleepiness Scale	Self-reported assessments of how alert one is currently feeling (1= wide awake, X=asleep)	Up to 60 days
Primary	Groningen Sleep Quality Scale	Assessment to understand sleep quality (0 = good sleep, maximum score of 14 points indicates poor sleep the night before)	Up to 60 days