Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Sleep Disordered Breathing in Marfan Syndrome: Susceptibility and Hemodynamics (MSB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03985657
Recruitment Status : Recruiting
First Posted : June 14, 2019
Last Update Posted : September 20, 2019
Sponsor:
Collaborators:
The Marfan Foundation
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:

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

Detailed Description:

Research Objective/Significance:

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.

Primary Outcomes:

  • Critical collapsing pressure (Pcrit) of the upper airway
  • Overnight measure of hemodynamic stress (blood pressure, heart rate, pleural pressure swings)
  • Apnea Hypopnea Index

Secondary Outcomes:

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
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)
Primary Purpose: Treatment
Official Title: Sleep Disordered Breathing in Marfan Syndrome: Susceptibility and Hemodynamics
Actual Study Start Date : June 6, 2018
Estimated Primary Completion Date : December 18, 2019
Estimated Study Completion Date : December 18, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Marfan Syndrome

Arm Intervention/treatment
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
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.




Primary Outcome Measures :
  1. Critical closing pressure of the upper airway (Pcrit) [ Time Frame: 2 nights ]
    Pressure at which the pharynx collapses during sleep in cmH2O.

  2. Mean arterial blood pressure [ Time Frame: 2 nights ]
    Overnight assessment of mean arterial blood pressure in mmHg.

  3. Mean Heart Rate [ Time Frame: 2 nights ]
    Overnight assessment of mean heart rate in beats per minute (bpm).

  4. Mean pleural pressure [ Time Frame: 2 nights ]
    Overnight assessment of mean pleural pressure swings in cmH2O.


Secondary Outcome Measures :
  1. 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.

  2. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Mariah Chaney 4105502233 mchaney7@jhmi.edu

Locations
Layout table for location information
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21224
Contact: Mariah Chaney    410-550-2233    mchaney7@jhmi.edu   
Sponsors and Collaborators
Johns Hopkins University
The Marfan Foundation
National Institutes of Health (NIH)
Investigators
Layout table for investigator information
Principal Investigator: Mudiaga Sowho Johns Hopkins University

Layout table for additonal information
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03985657     History of Changes
Other Study ID Numbers: IRB00157403
First Posted: June 14, 2019    Key Record Dates
Last Update Posted: September 20, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Sleep Apnea Syndromes
Apnea
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Marfan Syndrome
Arachnodactyly
Respiratory Aspiration
Snoring
Respiration Disorders
Respiratory Tract Diseases
Pathologic Processes
Dyssomnias
Nervous System Diseases
Respiratory Sounds
Signs and Symptoms, Respiratory
Signs and Symptoms
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Connective Tissue Diseases
Limb Deformities, Congenital
Musculoskeletal Abnormalities