Obstructive Sleep ApneaNCT02505594
Potential Mechanism of Exercise Impairment in OSA
An observational study of Obstructive Sleep Apnea, run by University of California, San Diego at 1 site in United States.
Trial summary
Obstructive sleep apnea (OSA) is a common disorder with major cardiovascular sequelae. A recent study confirmed that OSA is associated with impaired exercise capacity and increasing OSA severity predicts worsening exercise capacity, which is a marker of potential increased cardiovascular risk. Read more about this study
- Who is it for?
- Ages 30 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Obstructive Sleep Apnea
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2015to 9 May 2017
- Phase
- Observational
- 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 30 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Investigators will enroll 30 subjects with OSA (OSA group) and 30 subjects without OSA (control group). The detailed inclusion and exclusion criteria for subjects are listed below. Female subjects will be offered a urinary pregnancy test and only those documented to be non-pregnant will be studied.
Who may be able to join
- BMI < 30
- OSA group: diagnosis of untreated moderate-to-severe OSA (apnea-hypopnea index (AHI) ≥ 15 events/h).
- Control group: no OSA (AHI < 5 events/h).
Who cannot join
- Currently using Continuous Positive Airway Pressure (CPAP) or oral appliance treatment for OSA
- Uncontrolled cardiac co-morbidity, e.g. ischemic heart disease, heart failure, or valvular heart disease that would prevent exercise
- Uncontrolled pulmonary co-morbidity, e.g. asthma or chronic obstructive pulmonary disease (COPD)
- Comorbidities that may severely impair peripheral circulation, e.g. uncontrolled diabetes mellitus, or systemic scleroderma
- Neurological conditions limiting the ability to perform walking or cycling
- Orthopedic condition limiting the ability to perform walking or cycling
Show all 9Show fewer
- Current smokers, alcohol (> 3 oz/day) or use of illicit drugs.
- Psychiatric disorder, other than mild and controlled depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders.
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
San Diego, California, 92093
About this study
Official title: Pulmonary Vasoreactivity as a Potential Mechanism of Exercise Impairment in Obstructive Sleep Apnea
Obstructive sleep apnea (OSA) is a common disorder with major cardiovascular sequelae. A recent study confirmed that OSA is associated with impaired exercise capacity and increasing OSA severity predicts worsening exercise capacity, which is a marker of potential increased cardiovascular risk. However, potential mechanisms of decreased exercise capacity caused by OSA remain unclear. Several pathophysiologic mechanisms of OSA have been proposed and investigators hypothesize that endothelial dysfunction leading to exercise-induced right ventricular dysfunction and associated pulmonary hypertension is the potential mechanism for impaired exercise capacity in OSA.
Read the detailed description
Obstructive sleep apnea (OSA) is a common disorder with major cardiovascular sequelae, including increased systemic hypertension and strokes. OSA is highly prevalent among patients with cardiovascular disease (CVD), but OSA remains under-diagnosed, thus under-treated. Furthermore, a recent study confirmed that OSA is associated with impaired exercise capacity and increasing OSA severity predicts worsening exercise capacity, which is a marker of potential increased cardiovascular risk. However, potential mechanisms of decreased exercise capacity caused by OSA remain unclear.
Several pathophysiologic mechanisms of OSA have been proposed to explain this observation. Endothelial dysfunction is one mechanism that may result from OSA-related intermittent hypoxemia, heightened sympathetic activation, and increased blood pressure. Endothelial dysfunction is characterized by alteration of normal endothelial physiology consisting of a reduction in the bioavailability of vasodilators such as nitric oxide leading to impaired endothelium-depended vasodilation. Endothelial dysfunction has been consistently associated with an increased incidence of CVD. Recent evidence also suggests a correlation between endothelial function and exercise capacity.
In addition, endothelial dysfunction of pulmonary vasculature play an integral role in the pathogenesis of pulmonary hypertension (PH), which is defined by a mean pulmonary artery pressure exceeding 25 mm Hg. PH is associated with increased mortality and multiple morbidities including impaired exercise capacity. OSA has been formally recognized as a cause of PH by the World Health Organization (WHO) and the estimated prevalence of PH in patients with OSA is 17%. Repetitive nocturnal hypoxemia, increased sympathetic tone, and diminished endothelial dependent vaso-reactivity contribute to pulmonary artery hypoxic vasoconstriction, subsequently leading to pulmonary vasculature remodeling and PH. Recently, PH induced by exercise was described as part of the PH spectrum and may represent early, mild, PH that is still clinically relevant in many patients. To detect early PH in OSA patients may signify the importance of treatment and compliance for newly diagnosed OSA patients.
In summary, our hypothesis is that OSA patients may have endothelial dysfunction that leads to impaired exercise capacity via exercise-induced pulmonary hypertension. If our hypothesis is correct, non-invasive measurements of endothelial function could be used clinically to risk stratify patients or follow response to treatment.
- Conditions
- Obstructive Sleep Apnea
- Keywords
- Obstructive Sleep Apnea, Vasoreactivity, Endothelial function, Exercise
- Medical subject headings
- Sleep Apnea, Obstructive, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| OSA Group | Apnea-hypopnea index (AHI) ≥ 15 events/h | |
| Control Group | Apnea-hypopnea index (AHI) < 5 events/h |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endothelial function, as measured by endoPAT, between OSA patients and matched healthy controls
EndoPAT is a non-invasive measurement of endothelial function, using peripheral arterial tonometry. Exercise tolerance is measured by Cardiopulmonary exercise testing (CPET). Effects of OSA on exercise tolerance and endothelial function will be evaluated.
Measured: Baseline
Secondary outcomes (14)
Right ventricular systolic pressure (RVSP) in response to exercise
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Pulmonary systolic pressure (PASP) in response to exercise
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Right ventricular outflow track (RVOT) peak velocity in response to exercise
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Velocity time interval (VTI) in response to exercise
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Pulmonary artery acceleration time in response to exercise
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Systolic peak tricuspid myocardial annular velocity
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Diastolic peak tricuspid myocardial annular velocity
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Peak tricuspid myocardial annular velocity during isovolumic contraction
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Peak tricuspid myocardial annular velocity during isovolumic relaxation
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Right ventricular (RV) wall stress
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
3-D right ventricular ejection fraction (3D-RVEF)
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Systolic peak right ventricular (RV) strain
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Early diastolic peak right ventricular (RV) strain
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Late diastolic peak right ventricular (RV) strain
Measured by Echocardiogram, between OSA patients and matched healthy controls
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2015 (estimated)
- Study startJul 2015
- Primary completion9 May 2017
- Study completion9 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obstructive Sleep ApneaStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert L. Owens, University of California, San Diego
- Investigators
- Atul Malhotra, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02505594
- Sponsor's protocol ID
- UCSD150468
- Status last verified
- Jan 2018
- First submitted
- 12 Jul 2015
- Last updated
- 5 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pulmonary Vasoreactivity as a Potential Mechanism of Exercise Impairment in Obstructive Sleep Apnea
- ClinicalTrials.gov ID
- NCT02505594
- Acronym / sponsor ID
- UCSD150468
- Conditions
- Obstructive Sleep Apnea
- Keywords
- Obstructive Sleep Apnea, Vasoreactivity, Endothelial function, Exercise
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- Jul 2015
- Primary completion
- 9 May 2017 (actual)
- Study completion
- 9 May 2017 (actual)
- First posted
- 22 Jul 2015 (estimated)
- 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.
Obstructive sleep apnea (OSA) is a common disorder with major cardiovascular sequelae. A recent study confirmed that OSA is associated with impaired exercise capacity and increasing OSA severity predicts worsening exercise capacity, which is a marker of potential increased cardiovascular risk. However, potential mechanisms of decreased exercise capacity caused by OSA remain unclear. Several pathophysiologic mechanisms of OSA have been proposed and investigators hypothesize that endothelial dysfunction leading to exercise-induced right ventricular dysfunction and associated pulmonary hypertension is the potential mechanism for impaired exercise capacity in OSA.
Detailed description
Obstructive sleep apnea (OSA) is a common disorder with major cardiovascular sequelae, including increased systemic hypertension and strokes. OSA is highly prevalent among patients with cardiovascular disease (CVD), but OSA remains under-diagnosed, thus under-treated. Furthermore, a recent study confirmed that OSA is associated with impaired exercise capacity and increasing OSA severity predicts worsening exercise capacity, which is a marker of potential increased cardiovascular risk. However, potential mechanisms of decreased exercise capacity caused by OSA remain unclear.
Several pathophysiologic mechanisms of OSA have been proposed to explain this observation. Endothelial dysfunction is one mechanism that may result from OSA-related intermittent hypoxemia, heightened sympathetic activation, and increased blood pressure. Endothelial dysfunction is characterized by alteration of normal endothelial physiology consisting of a reduction in the bioavailability of vasodilators such as nitric oxide leading to impaired endothelium-depended vasodilation. Endothelial dysfunction has been consistently associated with an increased incidence of CVD. Recent evidence also suggests a correlation between endothelial function and exercise capacity.
In addition, endothelial dysfunction of pulmonary vasculature play an integral role in the pathogenesis of pulmonary hypertension (PH), which is defined by a mean pulmonary artery pressure exceeding 25 mm Hg. PH is associated with increased mortality and multiple morbidities including impaired exercise capacity. OSA has been formally recognized as a cause of PH by the World Health Organization (WHO) and the estimated prevalence of PH in patients with OSA is 17%. Repetitive nocturnal hypoxemia, increased sympathetic tone, and diminished endothelial dependent vaso-reactivity contribute to pulmonary artery hypoxic vasoconstriction, subsequently leading to pulmonary vasculature remodeling and PH. Recently, PH induced by exercise was described as part of the PH spectrum and may represent early, mild, PH that is still clinically relevant in many patients. To detect early PH in OSA patients may signify the importance of treatment and compliance for newly diagnosed OSA patients.
In summary, our hypothesis is that OSA patients may have endothelial dysfunction that leads to impaired exercise capacity via exercise-induced pulmonary hypertension. If our hypothesis is correct, non-invasive measurements of endothelial function could be used clinically to risk stratify patients or follow response to treatment.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OSA Group | – | –Apnea-hypopnea index (AHI) ≥ 15 events/h |
| Control Group | – | –Apnea-hypopnea index (AHI) < 5 events/h |
Who may qualify
- Ages
- 30 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Investigators will enroll 30 subjects with OSA (OSA group) and 30 subjects without OSA (control group). The detailed inclusion and exclusion criteria for subjects are listed below. Female subjects will be offered a urinary pregnancy test and only those documented to be non-pregnant will be studied.
Key inclusion criteria (3 listed)
- BMI < 30
- OSA group: diagnosis of untreated moderate-to-severe OSA (apnea-hypopnea index (AHI) ≥ 15 events/h).
- Control group: no OSA (AHI < 5 events/h).
Key exclusion criteria (9 listed)
- Currently using Continuous Positive Airway Pressure (CPAP) or oral appliance treatment for OSA
- Uncontrolled cardiac co-morbidity, e.g. ischemic heart disease, heart failure, or valvular heart disease that would prevent exercise
- Uncontrolled pulmonary co-morbidity, e.g. asthma or chronic obstructive pulmonary disease (COPD)
- Comorbidities that may severely impair peripheral circulation, e.g. uncontrolled diabetes mellitus, or systemic scleroderma
- Neurological conditions limiting the ability to perform walking or cycling
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Endothelial function, as measured by endoPAT, between OSA patients and matched healthy controls
Time frame: Baseline
EndoPAT is a non-invasive measurement of endothelial function, using peripheral arterial tonometry. Exercise tolerance is measured by Cardiopulmonary exercise testing (CPET). Effects of OSA on exercise tolerance and endothelial function will be evaluated.
14 secondary outcomes
Right ventricular systolic pressure (RVSP) in response to exercise
Time frame: Baseline
Pulmonary systolic pressure (PASP) in response to exercise
Time frame: Baseline
Right ventricular outflow track (RVOT) peak velocity in response to exercise
Time frame: Baseline
Velocity time interval (VTI) in response to exercise
Time frame: Baseline
Pulmonary artery acceleration time in response to exercise
Time frame: Baseline
Systolic peak tricuspid myocardial annular velocity
Time frame: Baseline
Diastolic peak tricuspid myocardial annular velocity
Time frame: Baseline
Peak tricuspid myocardial annular velocity during isovolumic contraction
Time frame: Baseline
Peak tricuspid myocardial annular velocity during isovolumic relaxation
Time frame: Baseline
Right ventricular (RV) wall stress
Time frame: Baseline
3-D right ventricular ejection fraction (3D-RVEF)
Time frame: Baseline
Systolic peak right ventricular (RV) strain
Time frame: Baseline
Early diastolic peak right ventricular (RV) strain
Time frame: Baseline
Late diastolic peak right ventricular (RV) strain
Time frame: Baseline
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 5 Jan 2018.
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Supplemental Oxygen for Sleep-Disordered Breathing in Adults With Chronic Opioid Use.
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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.
Atul Malhotra, MD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obstructive Sleep Apnea, run by University of California, San Diego 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 3 inclusion and 9 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 5 Jan 2018. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Endothelial function, as measured by endoPAT, between OSA patients and matched healthy controls (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jan 2018.