Sleep ApneaEarly Phase 1NCT05146089

Reflex Responses to Intermittent Hypoxia in Humans: Mechanisms and Consequences

A Early Phase 1 study testing Hypoxic exposure, modified Oxford test and Oral Bosentan 62.5 mg in people with Sleep Apnea and Healthy, run by University of Missouri-Columbia at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The overall goal of this project is to better understand the effect of intermittent hypoxia (IH) on sympathetic neuronal discharge patterns in humans, as well as mechanisms that mediate persistent sympathoexcitation with IH. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Sleep Apnea, Healthy, Vasoconstriction
What is being tested?: Hypoxic exposure, modified Oxford test and Oral Bosentan 62.5 mg
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 54 participants
Where: 2 sitesUnited States
Study dates: 20 Dec 2016to 12 Apr 2021
Phase: Early Phase 1
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 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

healthy adult men and women;
18-45 years of age;
BMI <30 kg/m2;
non-pregnant/non-breastfeeding;
non-smokers.

Who cannot join

Subjects will be excluded if they are:
taking any medications known to affect the cardiovascular or autonomic nervous system (e.g. alpha-blockers, beta-blockers, etc);
Apnea Hypopnea Index >10 events/hr
Self-reported history of:
hepatic, renal, pulmonary, cardiovascular, or neurological disease;
stroke or neurovascular disease;

Show all 12Show fewer

bleeding/clotting disorders;
sleep apnea or other sleep disorders;
diabetes;
smoking;
history of alcoholism or substance abuse;
hypertension.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

University of Missouri-Columbia
Columbia, Missouri, 65211
Mayo Clinic
Rochester, Missouri, 55902

Other trials in United States

About this study

Read the detailed description

Sleep apnea is the most common form of sleep disordered breathing and patients with sleep apnea exhibit persistent activation of the sympathetic nervous system. Sympathoexcitation is also the final common pathway for a host of complications in conditions like obesity, hypertension, sleep apnea, and heart failure and plays a significant role in predicting negative clinical outcomes and deteriorating cardiovascular health. However, the mechanisms of sympathoexcitation with sleep apnea are poorly understood and thus make effective therapeutic approaches difficult to develop.

Intermittent hypoxia (IH) has been implicated in animal models as the primary stimulus for evoking increases in sympathetic activity with recurrent apneas. Thus, the overall goal of this application is to better understand the effect of IH on sympathetic discharge patterns in humans as well as the mechanisms mediating persistent sympathoexcitation with IH. By better understanding the effect of IH on sympathoexcitation, targeted therapeutic approaches might be devised to mitigate the effects of sympathetic over-activity on the cardiovascular system in conditions such as sleep apnea.

Conditions: Sleep Apnea, Healthy, Vasoconstriction, Vasodilation
Being tested: Hypoxic exposure, modified Oxford test, Oral Bosentan 62.5 mg, Hypoxic ventilatory response test
Medical subject headings: Sleep Apnea Syndromes, Aneurysm

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Hypoxic exposureOther
30 minutes of intermittent hypoxia achieved using breaths of low oxygen air (5% oxygen) followed by room air through a mask.
modified Oxford testOther
An intravenous bolus of sodium nitroprusside (100 μg) will be given to decrease blood pressure, followed 1 minute later by a bolus of phenylephrine (150 μg) to increase blood pressure, occurring before and after intermittent hypoxia exposure.
Oral Bosentan 62.5 mgDrug
Prior to completion of visit 2, male subjects will consume 62.5 mg twice daily for 3 days as well as the morning of the study visit (7 pills) at home and experimental sessions will be performed 3 hours after oral intake of the final dose.
Hypoxic ventilatory response testOther
Hypoxia will be achieved using breaths of low oxygen air (5% oxygen) followed by room air through a mask. This will be repeated 4-5 times per test, occurring before and after intermittent hypoxia exposure.

Study groups in NCT05146089
Study group	Role	What they receive
Hypoxia Exposure	Experimental	Men and women will be exposed to acute intermittent hypoxic episodes. Receives: Other: Hypoxic exposure; Other: modified Oxford test; Drug: Oral Bosentan 62.5 mg; Other: Hypoxic ventilatory response test

What is being measured

The primary outcome is the main question the study is designed to answer.

Muscle sympathetic nerve activity (MSNA)
MSNA burst incidence (bursts/100 heart beats)
Measured: Change from baseline after hypoxia exposure

Secondary outcomes (1)

Arterial blood pressure
Systolic blood pressure, Diastolic blood pressure, Mean blood pressure
Measured: Change from baseline after hypoxia exposure

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Dec 201612 Apr 2021

First posted6 Dec 2021
Study start20 Dec 2016
Primary completion8 Sep 2018
Study completion12 Apr 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Sleep ApneaStudies of the same condition, open and under way.
More trials run by University of Missouri-ColumbiaThe sponsor's other registered studies.
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: Early Phase 1
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Model description: Subjects will be asked to complete 1 1-hour screening visit, 1 overnight at-home monitoring, and 1 (women) or 2 (men) 5-hour study visits. Subjects will not be blinded to study condition and all subjects will serve as their own controls. All study visits will be separated by a minimum of 1 week and will occur at the same time of day.
Masking: None (open label)
Enrolment: 54 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05146089
Sponsor's protocol ID: 2007973
Other IDs: K99HL130339, R00HL130339
Status last verified: Nov 2021
First submitted: 2 Nov 2021
Last updated: 6 Dec 2021
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Locus Coeruleus and CCHS (Congenital Central Hypoventilation Syndrome)
Ondine Syndrome (Congenital Central Hypoventilation Syndrome)
RecruitingObservational study
Development and Validation of a Multimodal Deep Learning Model Using Peripheral Oxygen Saturation and Ballistocardiography Signals for Predicting Apnea-Hypopnea Index in Obstructive Sleep Apnea
Obstructive Sleep Apnea
Not yet recruiting
Comprehensive Opioid Management and Breathing During Sleep
Sleep-Disordered Breathing, Chronic Opioid Use
Recruiting
Janus II Feasibility
Sleep Apnea
RecruitingPhase 3
A Study to Learn About the Monthly Dosing Study Medicine Called Berobenatide in Adults With Breathing Problems During Sleep and Overweight or Obesity Who Do Not Use a Breathing Machine (PAP) (VESPER-OSA 2)
Apnea, Sleep Disorders

All Sleep Apnea trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Reflex Responses to Intermittent Hypoxia in Humans: Mechanisms and Consequences
ClinicalTrials.gov ID: NCT05146089
Acronym / sponsor ID: 2007973
Conditions: Sleep Apnea, Healthy, Vasoconstriction, Vasodilation
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 54 participants (actual)
Lead sponsor: University of Missouri-ColumbiaUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI), Mayo Clinic
Study start: 20 Dec 2016 (actual)
Primary completion: 8 Sep 2018 (actual)
Study completion: 12 Apr 2021 (actual)
First posted: 6 Dec 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.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Subjects will be asked to complete 1 1-hour screening visit, 1 overnight at-home monitoring, and 1 (women) or 2 (men) 5-hour study visits. Subjects will not be blinded to study condition and all subjects will serve as their own controls. All study visits will be separated by a minimum of 1 week and will occur at the same time of day.

Arm	Type	Receives
Hypoxia Exposure	Experimental	Other: Hypoxic exposure, Other: modified Oxford test, Drug: Oral Bosentan 62.5 mg, Other: Hypoxic ventilatory response testMen and women will be exposed to acute intermittent hypoxic episodes.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

healthy adult men and women;
18-45 years of age;
BMI <30 kg/m2;
non-pregnant/non-breastfeeding;
non-smokers.

Key exclusion criteria (12 listed)

taking any medications known to affect the cardiovascular or autonomic nervous system (e.g. alpha-blockers, beta-blockers, etc);
Apnea Hypopnea Index >10 events/hr
hepatic, renal, pulmonary, cardiovascular, or neurological disease;
stroke or neurovascular disease;
bleeding/clotting disorders;

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
Hypoxic exposure30 minutes of intermittent hypoxia achieved using breaths of low oxygen air (5% oxygen) followed by room air through a mask.	Other	Hypoxia Exposure
modified Oxford testAn intravenous bolus of sodium nitroprusside (100 μg) will be given to decrease blood pressure, followed 1 minute later by a bolus of phenylephrine (150 μg) to increase blood pressure, occurring before and after intermittent hypoxia exposure.	Other	Hypoxia Exposure
Oral Bosentan 62.5 mgPrior to completion of visit 2, male subjects will consume 62.5 mg twice daily for 3 days as well as the morning of the study visit (7 pills) at home and experimental sessions will be performed 3 hours after oral intake of the final dose.	Drug	Hypoxia Exposure
Hypoxic ventilatory response testHypoxia will be achieved using breaths of low oxygen air (5% oxygen) followed by room air through a mask. This will be repeated 4-5 times per test, occurring before and after intermittent hypoxia exposure.	Other	Hypoxia Exposure

Primary outcome

Muscle sympathetic nerve activity (MSNA)
Time frame: Change from baseline after hypoxia exposure
MSNA burst incidence (bursts/100 heart beats)

1 secondary outcome

Arterial blood pressure
Time frame: Change from baseline after hypoxia exposure

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 6 Dec 2021.
Individual participant dataSharing planned: Undecided

Related trials for Sleep Apnea

RecruitingObservational study
Locus Coeruleus and CCHS (Congenital Central Hypoventilation Syndrome)
Ondine Syndrome (Congenital Central Hypoventilation Syndrome)
RecruitingObservational study
Development and Validation of a Multimodal Deep Learning Model Using Peripheral Oxygen Saturation and Ballistocardiography Signals for Predicting Apnea-Hypopnea Index in Obstructive Sleep Apnea
Obstructive Sleep Apnea
Not yet recruiting
Comprehensive Opioid Management and Breathing During Sleep
Sleep-Disordered Breathing, Chronic Opioid Use
Recruiting
Janus II Feasibility
Sleep Apnea
RecruitingPhase 3
A Study to Learn About the Monthly Dosing Study Medicine Called Berobenatide in Adults With Breathing Problems During Sleep and Overweight or Obesity Who Do Not Use a Breathing Machine (PAP) (VESPER-OSA 2)
Apnea, Sleep Disorders

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.

Jacqueline K Limberg, Ph.D. principal investigator

University of Missouri-Columbia

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 5 inclusion and 12 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 6 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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?

Muscle sympathetic nerve activity (MSNA) (time frame: Change from baseline after hypoxia exposure). 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 NCT05146089.

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 6 Dec 2021.