Effects of Naltrexone on Nocturnal Breathing Patterns at Altitude
Condition: Altitude; Sleep Apnea, Central
MeSH terms: Sleep Apnea, Central
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Naltrexone Pill; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 50 mg PO one-time only; Matching placebo for naltrexone
Intervention MeSH terms: Naltrexone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Altitude; Periodic Breathing; Sleep