Effects of Naltrexone on Nocturnal Breathing Patterns at Altitude

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.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea, Central; Altitude
• Intervention / Treatment: Drug: Naltrexone Pill; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92357
      • VA Loma Linda Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Study drug naltrexone hydrochloride; 50 mg Naltrexone PO	Drug: Naltrexone Pill; 50 mg PO one-time only
Placebo Comparator: Matching placebo for naltrexone hydrochloride; Matching placebo for Study Drug Naltrexone	Drug: Placebo; Matching placebo for naltrexone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nighttime oxygen saturation	Change from baseline in nighttime SpO2	Up to 60 days
Periodic Breathing	Change from baseline in portion of night spent with periodic breathing	Up to 60 days
Epworth Sleepiness Scale	Subjective measurement of one's daytime sleepiness (0 = less sleepy, 24= excessively sleepy)	Up to 60 days
Stanford Sleepiness Scale	Self-reported assessments of how alert one is currently feeling (1= wide awake, X=asleep)	Up to 60 days
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

Collaborators and Investigators

• Sponsor: VA Loma Linda Health Care System
• Investigators: Principal Investigator: James D Anholm, MD, VA Loma Linda Healthcare System

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2021
• Primary Completion (Actual): October 17, 2021
• Study Completion (Actual): October 17, 2021

Study Registration Dates

• First Submitted: August 20, 2021
• First Submitted That Met QC Criteria: September 2, 2021
• First Posted (Actual): September 8, 2021

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Sleep; Altitude; Periodic Breathing
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Central; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: 1392

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