Hemodynamics Response to Upper Airway Obstruction in Marfan Syndrome (MSB)

Sleep Disordered Breathing in Marfan Syndrome: Susceptibility and Hemodynamics

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.

Study Overview

• Status: Completed
• Conditions: Snoring; Sleep-disordered Breathing
• Intervention / Treatment: Device: CPAP

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)

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Baseline Sleep Study; Baseline sleep polysomnography will involve the collection of electroencephalogram, electromyogram, electrocardiogram, airflow, heart rate, blood pressure, and pleural pressure during sleep with no CPAP. Participants in this arm would switch to CPAP within one week of the study.	Device: CPAP; 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.
EXPERIMENTAL: CPAP Sleep Study; Participants will be treated with continuous positive airway pressure to relieve sleep-disordered breathing. Participants in this arm would switch to Baseline study within one week of the study.	Device: CPAP; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pleural Pressure (Pes)	Pleural pressure (Pes) in mmHg monitored using an esophageal catheter.	Overnight on both CPAP and No CPAP nights
Mean Arterial Blood Pressure (MAP)	Continuous blood pressure monitored using a non-invasive finger cuff. Data captured in mmHg.	Overnight on both Baseline and CPAP studies

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Augmentation Index (AI)	The AI (measured as "percentage of pulse pressure") was assessed in the morning after both Baseline and CPAP studies. It is a measure of arterial stiffness that represents the degree of and can range from -10% to +10% in healthy individuals, with values generally higher in females and increases with age.	15 minutes in the morning post Baseline and CPAP studies
Reactive Hyperemia Index (RHI)	The RHI is a measure of endothelial function that was measured in the morning after both Baseline and CPAP studies. It is unitless and scored on a range of 1 to 3 in healthy individuals with lower values indicating poor endothelial function.	15 minutes

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institutes of Health (NIH); The Marfan Foundation
• Investigators: Principal Investigator: Mudiaga Sowho, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 6, 2018
• Primary Completion (ACTUAL): December 6, 2019
• Study Completion (ACTUAL): December 6, 2019

Study Registration Dates

• First Submitted: June 11, 2019
• First Submitted That Met QC Criteria: June 11, 2019
• First Posted (ACTUAL): June 14, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 28, 2020
• Last Update Submitted That Met QC Criteria: December 2, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Signs and Symptoms, Respiratory; Bone Diseases; Respiratory Sounds; Heart Defects, Congenital; Cardiovascular Abnormalities; Musculoskeletal Abnormalities; Abnormalities, Multiple; Bone Diseases, Developmental; Limb Deformities, Congenital; Sleep Apnea Syndromes; Respiratory Aspiration; Snoring; Marfan Syndrome; Arachnodactyly
• Other Study ID Numbers: IRB00157403

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes