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出境医 / 临床实验 / Hemodynamics Response to Upper Airway Obstruction in Marfan Syndrome (MSB)

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

Study Description
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.


Condition or disease Intervention/treatment Phase
Sleep-disordered Breathing Snoring Device: CPAP Not Applicable

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 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
Actual Primary Completion Date : December 6, 2019
Actual Study Completion Date : December 6, 2019
Arms and Interventions
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.
Outcome Measures
Primary Outcome Measures :
  1. Pleural Pressure (Pes) [ Time Frame: Overnight on both CPAP and No CPAP nights ]
    Pleural pressure (Pes) in mmHg monitored using an esophageal catheter.

  2. Mean Arterial Blood Pressure (MAP) [ Time Frame: Overnight on both Baseline and CPAP studies ]
    Continuous blood pressure monitored using a non-invasive finger cuff. Data captured in mmHg.


Secondary Outcome Measures :
  1. Augmentation Index (AI) [ Time Frame: 15 minutes in the morning post Baseline and CPAP studies ]
    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.

  2. Reactive Hyperemia Index (RHI) [ Time Frame: 15 minutes ]
    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.


Eligibility Criteria
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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
Contacts and Locations

Locations
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United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
The Marfan Foundation
National Institutes of Health (NIH)
Investigators
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Principal Investigator: Mudiaga Sowho Johns Hopkins University
Tracking Information
First Submitted Date  ICMJE June 11, 2019
First Posted Date  ICMJE June 14, 2019
Results First Submitted Date  ICMJE December 2, 2020
Results First Posted Date  ICMJE December 28, 2020
Last Update Posted Date December 28, 2020
Actual Study Start Date  ICMJE June 6, 2018
Actual Primary Completion Date December 6, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 2, 2020)
  • Pleural Pressure (Pes) [ Time Frame: Overnight on both CPAP and No CPAP nights ]
    Pleural pressure (Pes) in mmHg monitored using an esophageal catheter.
  • Mean Arterial Blood Pressure (MAP) [ Time Frame: Overnight on both Baseline and CPAP studies ]
    Continuous blood pressure monitored using a non-invasive finger cuff. Data captured in mmHg.
Original Primary Outcome Measures  ICMJE
 (submitted: June 11, 2019)
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2020)
  • Augmentation Index (AI) [ Time Frame: 15 minutes in the morning post Baseline and CPAP studies ]
    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.
  • Reactive Hyperemia Index (RHI) [ Time Frame: 15 minutes ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2019)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hemodynamics Response to Upper Airway Obstruction in Marfan Syndrome
Official Title  ICMJE Sleep Disordered Breathing in Marfan Syndrome: Susceptibility and Hemodynamics
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)
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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
Condition  ICMJE
  • Sleep-disordered Breathing
  • Snoring
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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.
    Intervention: Device: CPAP
  • 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.
    Intervention: Device: CPAP
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 2, 2020) 		31
Original Estimated Enrollment  ICMJE
 (submitted: June 11, 2019) 		60
Actual Study Completion Date  ICMJE December 6, 2019
Actual Primary Completion Date December 6, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03985657
Other Study ID Numbers  ICMJE IRB00157403
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE
  • The Marfan Foundation
  • National Institutes of Health (NIH)
Investigators  ICMJE
Principal Investigator: Mudiaga Sowho Johns Hopkins University
PRS Account Johns Hopkins University
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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