Sleep Disordered Breathing in Marfan Syndrome: Susceptibility and Hemodynamics (MSB)
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|ClinicalTrials.gov Identifier: NCT03985657|
Recruitment Status : Recruiting
First Posted : June 14, 2019
Last Update Posted : June 11, 2020
The main thrust of the research is based on evidence that 1) there is a higher prevalence of obstructive sleep apnea (OSA) in patients with Marfan syndrome (MFS) and 2) that there could be an association between OSA and aortic dissection, the main cause of morbidity and mortality in this patient subset.
The increased prevalence is thought to be due to increased collapsibility of the upper airway but this has not been characterized physiologically. Also, it is thought that the hemodynamic stress associated with OSA may contribute to aortic disease in MFS.
In this project therefore, the investigators will estimate the closing pressure of the upper airway in MFS patients to determine susceptibility. The investigators will also examine the hemodynamic responses in periods of obstructed breathing and explore the relationship between these responses and aortic vascular parameters in MFS.
|Condition or disease||Intervention/treatment||Phase|
|Sleep-disordered Breathing Snoring||Device: CPAP||Not Applicable|
The goal of this proposal is to 1) determine whether higher susceptibility for UAO during sleep (ranging from snoring to hypopneas and frank apneas) in MFS is partly mediated by increased critical closing pressure (Pcrit) of the upper airway and 2) to determine the effect of upper airway obstruction (UAO) on hemodynamics and aortic vascular properties in MFS. Hence insights gained from this protocol may explain the increased prevalence of Sleep Disordered Breathing (SDB) in MFS and how sleep apnea and snoring could worsen aortic disease and other cardiovascular problems in MFS. This knowledge may also extend to persons with similar connective tissue diseases like Loeys-Dietz syndrome, vascular type Ehlers-Danlos syndrome and Arterial tortuosity syndrome who may also have increased SDB prevalence.
Specific Aim 1a: The investigators will determine susceptibility to upper airway obstruction (UAO) in MFS persons based on structural upper airway properties (Pcrit).
Specific Aim 1b: The investigators will quantify overnight exposure to UAO estimated by both the apnea hypopnea index and a composite measure of pleural pressure swings in both MFS.
Specific Aim 2a: To quantify the hemodynamic responses to UAO during sleep in persons with MFS.
Specific Aim 2b: To provide exploratory data on the relationship between the hemodynamic response to UAO and aortic vascular properties in MFS persons.
- Critical collapsing pressure (Pcrit) of the upper airway
- Overnight measure of hemodynamic stress (blood pressure, heart rate, pleural pressure swings)
- Apnea Hypopnea Index
- Changes in diurnal markers of a hemodynamic stress (augmentation index, reactive hyperemia index)
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||Participants will be assigned to a Baseline polysomnography and CPAP polysomnography in a randomized fashion. Participants will then be switched to the second polysomnography within 14 days of the first. The baseline polysomnography represents the exposure to sleep disordered breathing and the CPAP polysomnography represents the relief of the exposure. Markers of hemodynamic stress will be assessed in the morning after both studies.|
|Masking:||None (Open Label)|
|Official Title:||Sleep Disordered Breathing in Marfan Syndrome: Susceptibility and Hemodynamics|
|Actual Study Start Date :||June 6, 2018|
|Actual Primary Completion Date :||December 6, 2019|
|Estimated Study Completion Date :||December 6, 2022|
No Intervention: Baseline Sleep Study
Baseline sleep polysomnography will involve collection of electroencephalogram, electromyogram, electrocardiogram, airflow, heart rate, blood pressure and pleural pressure during sleep with no CPAP.
Experimental: CPAP Sleep Study
Participants will be treated with continuous positive airway pressure to relieve sleep disordered breathing
Continuous positive airway pressure (CPAP). Room air at pressures between 6-8 centimeters of water (cmH2O) delivered via heated humidified tubing and a nasal mask.
- Critical closing pressure of the upper airway (Pcrit) [ Time Frame: 2 nights ]Pressure at which the pharynx collapses during sleep in cmH2O.
- Mean arterial blood pressure [ Time Frame: 2 nights ]Overnight assessment of mean arterial blood pressure in mmHg.
- Mean Heart Rate [ Time Frame: 2 nights ]Overnight assessment of mean heart rate in beats per minute (bpm).
- Mean pleural pressure [ Time Frame: 2 nights ]Overnight assessment of mean pleural pressure swings in cmH2O.
- Arterial stiffness as assessed by the Augmentation Index [ Time Frame: 15 minutes ]Morning (post night study) assessment of augmentation Index a measure of arterial stiffness. It can range from -10% to +30% in healthy individuals, with values increasing with age and arterial stiffness.
- Endothelial function as assessed by Hyperemia Index [ Time Frame: 15 minutes ]Morning (post night study) assessment of reactive hyperemia index a measure of endothelial function. It is unitless and can range from 1 to 3 in healthy individuals with lower values indicating poor endothelial function.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03985657
|Contact: Mariah Chaneyfirstname.lastname@example.org|
|United States, Maryland|
|Johns Hopkins University||Recruiting|
|Baltimore, Maryland, United States, 21224|
|Contact: Mariah Chaney 410-550-2233 email@example.com|
|Principal Investigator:||Mudiaga Sowho||Johns Hopkins University|