AltitudePhase 4NCT05037032
Effects of Naltrexone on Nocturnal Breathing Patterns at Altitude
A Phase 4 study testing Naltrexone Pill in people with Altitude and Sleep Apnea, Central, run by VA Loma Linda Health Care System at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Altitude, Sleep Apnea, Central
- What is being tested?
- Naltrexone Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Aug 2021to 17 Oct 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy males or females
- Age 18 to 35 years of age
- Body-mass index (BMI) ≤ 27
- At least two weeks after full vaccination for Sars-CoV-2. Proof of vaccination will be determined by the investigators.
Who cannot join
- Current smoker or significant past smoking history (≥ 10 pack-years)
- 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
- History of obstructive sleep apnea, or other history of sleep disordered breathing, or previous use of nighttime continuous positive airway pressure (CPAP)
- Any history of chronic opioid use or prior abuse history
- Any history of alcohol abuse
- Use of any opioid substance (prescribed or otherwise) within 2-weeks of study enrollment
- 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.
- Recent (within 3 weeks) exposure to altitudes ≥ 3,500 m at time of 1st altitude trip
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Loma Linda Healthcare System
Loma Linda, California, 92357
About this study
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.
Read the 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.
- Conditions
- Altitude, Sleep Apnea, Central
- Being tested
- Naltrexone Pill, Placebo
- Keywords
- Altitude, Periodic Breathing, Sleep
- Medical subject headings
- Sleep Apnea, Central
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naltrexone PillDrug
50 mg PO one-time only
PlaceboDrug
Matching placebo for naltrexone
| Study group | Role | What they receive |
|---|---|---|
| Study drug naltrexone hydrochloride | Active comparator | 50 mg Naltrexone PO Receives: Drug: Naltrexone Pill |
| Matching placebo for naltrexone hydrochloride | Placebo comparator | Matching placebo for Study Drug Naltrexone Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nighttime oxygen saturation
Change from baseline in nighttime SpO2
Measured: Up to 60 days
Periodic Breathing
Change from baseline in portion of night spent with periodic breathing
Measured: Up to 60 days
Epworth Sleepiness Scale
Subjective measurement of one's daytime sleepiness (0 = less sleepy, 24= excessively sleepy)
Measured: Up to 60 days
Stanford Sleepiness Scale
Self-reported assessments of how alert one is currently feeling (1= wide awake, X=asleep)
Measured: 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)
Measured: Up to 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2021
- Study start8 Aug 2021
- Primary completion17 Oct 2021
- Study completion17 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AltitudeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Loma Linda Health Care System
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, James D. Anholm, M.D., VA Loma Linda Health Care System
- Investigators
- James D Anholm, MD, Principal investigator, VA Loma Linda Healthcare System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05037032
- Sponsor's protocol ID
- 1392
- Status last verified
- Apr 2023
- First submitted
- 20 Aug 2021
- Last updated
- 26 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Foster K, Anholm JD, Foster G, Thapamagar S, Subedi P. Effects of Naltrexone on Sleep Quality and Periodic Breathing at High Altitude. High Alt Med Biol. 2025 Mar;26(1):13-19. doi: 10.1089/ham.2024.0023. Epub 2024 Jul 5.
PubMed 38966963
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Naltrexone on Nocturnal Breathing Patterns at Altitude
- ClinicalTrials.gov ID
- NCT05037032
- Acronym / sponsor ID
- 1392
- Conditions
- Altitude, Sleep Apnea, Central
- Keywords
- Altitude, Periodic Breathing, Sleep
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- VA Loma Linda Health Care SystemUS federal agency
- Study start
- 8 Aug 2021 (actual)
- Primary completion
- 17 Oct 2021 (actual)
- Study completion
- 17 Oct 2021 (actual)
- First posted
- 8 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study drug naltrexone hydrochloride | Active comparator | Drug: Naltrexone Pill50 mg Naltrexone PO |
| Matching placebo for naltrexone hydrochloride | Placebo comparator | Drug: PlaceboMatching placebo for Study Drug Naltrexone |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy males or females
- Age 18 to 35 years of age
- Body-mass index (BMI) ≤ 27
- At least two weeks after full vaccination for Sars-CoV-2. Proof of vaccination will be determined by the investigators.
Key exclusion criteria (8 listed)
- Current smoker or significant past smoking history (≥ 10 pack-years)
- 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
- History of obstructive sleep apnea, or other history of sleep disordered breathing, or previous use of nighttime continuous positive airway pressure (CPAP)
- Any history of chronic opioid use or prior abuse history
- Any history of alcohol abuse
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Naltrexone Pill50 mg PO one-time only | Drug | Study drug naltrexone hydrochloride |
| PlaceboMatching placebo for naltrexone | Drug | Matching placebo for naltrexone hydrochloride |
Primary outcome
Nighttime oxygen saturation
Time frame: Up to 60 days
Change from baseline in nighttime SpO2
Periodic Breathing
Time frame: Up to 60 days
Change from baseline in portion of night spent with periodic breathing
Epworth Sleepiness Scale
Time frame: Up to 60 days
Subjective measurement of one's daytime sleepiness (0 = less sleepy, 24= excessively sleepy)
Stanford Sleepiness Scale
Time frame: Up to 60 days
Self-reported assessments of how alert one is currently feeling (1= wide awake, X=asleep)
Groningen Sleep Quality Scale
Time frame: Up to 60 days
Assessment to understand sleep quality (0 = good sleep, maximum score of 14 points indicates poor sleep the night before)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2023.
- Derived from this study: PubMed 38966963Foster K, Anholm JD, Foster G, Thapamagar S, Subedi P. Effects of Naltrexone on Sleep Quality and Periodic Breathing at High Altitude. High Alt Med Biol. 2025 Mar;26(1):13-19. doi: 10.1089/ham.2024.0023. Epub 2024 Jul 5.
- Individual participant dataSharing planned: No
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Optimization of Two-Indicator Screening Protocol for Neonatal Congenital Heart Disease at High Altitude
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James D Anholm, MD principal investigator
VA Loma Linda Healthcare System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Naltrexone Pill in people with Altitude and Sleep Apnea, Central, run by VA Loma Linda Health Care System at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Nighttime oxygen saturation (time frame: Up to 60 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05037032, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2023.