Clinical trial NCT03985657: Hemodynamics Response to Upper Airway Obstruction in Marfan Syndrome
Official title: Sleep Disordered Breathing in Marfan Syndrome: Susceptibility and Hemodynamics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sleep-disordered Breathing
Snoring
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: The Marfan Foundation
name: National Institutes of Health (NIH)
First posted: 2019-06-14
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

Brief summary: Upper airway obstruction (UAO) is an unrecognized source of hemodynamic stress that may contribute to aortic adverse events in persons with Marfan Syndrome (MFS). UAO occurs during snoring and sleep apnea and is characterized by repetitive partial or complete obstruction of the upper airway during sleep. These obstructive breathing events lead to intermittent surges in blood pressure (BP) REF and large decreases in pleural pressure (Pes), thereby increasing the trans-mural aortic pressure (TMP) and imposing mechanical stress on the aorta during sleep. Although UAO is known to increase mechanical stress on the aorta, the magnitude of the increase is not known for persons with MFS.

In this project, therefore, the investigators will also examine the changes in Pes and BP responses in periods of obstructed breathing and compare the diurnal markers or vascular stress between Baseline and CPAP studies in MFS persons.

Detailed description: Research Objective/Significance:

Specific Aim 1a: To quantify the Pes and BP during periods with and without UAO during sleep in persons with MFS.

Specific Aim 1b: To examine the effect of CPAP treatment of UAO on Pes and BP in MFS persons.

Specific Aim 2: To examine the effect of CPAP treatment of UAO on daytime markers of hemodynamic stress (augmentation index, reactive hyperemia index) in MFS persons.

Primary Outcomes:

* Overnight measure of hemodynamic stress (blood pressure, pleural pressure swings)

Secondary Outcomes:

* Changes in diurnal markers of hemodynamic stress (augmentation index, reactive hyperemia index)

Eligibility criteria: Inclusion Criteria:

People with Marfan syndrome.

* Age ≥ 18yrs
* Able and willing to provide informed consent
* Willing to sleep connected to research apparatus

Exclusion Criteria:

* Unstable cardiovascular disease (CHF, myocardial infarction or revascularization procedures, and unstable arrhythmias)
* Uncontrolled hypertension (BP \> 190/110)
* Underlying obstructive or other intrinsic lung disease
* Renal failure on dialysis
* Cirrhosis
* Pregnancy

Primary outcomes:
measure: Pleural Pressure (Pes)
timeFrame: Overnight on both CPAP and No CPAP nights
measure: Mean Arterial Blood Pressure (MAP)
timeFrame: Overnight on both Baseline and CPAP studies
Secondary outcomes:
measure: Augmentation Index (AI)
timeFrame: 15 minutes in the morning post Baseline and CPAP studies
measure: Reactive Hyperemia Index (RHI)
timeFrame: 15 minutes
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Mudiaga Sowho
role: PRINCIPAL_INVESTIGATOR
References: