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| Name | Class |
|---|---|
| The Marfan Foundation | OTHER |
| National Institutes of Health (NIH) | NIH |
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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.
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:
Secondary Outcomes:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Baseline Sleep Study | Active Comparator | 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. |
|
| CPAP Sleep Study | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CPAP | Device | 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. |
|
| 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 |
| 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 |
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Inclusion Criteria:
People with Marfan syndrome.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mudiaga Sowho | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University | Baltimore | Maryland | 21224 | United States |
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193 persons with Marfan syndrome were screened. Persons were recruited from the Johns Hopkins Marfan Clinic and the external Marfan Community via the Marfan foundation. Inclusion was based on a clinical diagnosis of Marfan syndrome (Ghent Criteria) or genetic testing. Persons were excluded if they had any chronic lung disease, other sleep disorders aside from sleep apnea, were on blood thinners, or had uncontrolled blood pressure. Recruitment occurred between 09/2018 and 11/2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Baseline Sleep Study | Baseline sleep polysomnography involved the monitoring 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 Baseline Sleep Study. |
| FG001 | CPAP Sleep Study | In a randomized cross-over fashion, participants were treated with continuous positive airway pressure (CPAP) on a separate night. Room air at pressures between 6-9 centimeters of water (cmH2O) were delivered via heated humidified tubing and a nasal mask. Participants in this arm would switch to Baseline Sleep Study within one week of the CPAP Sleep Study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intervention 1 (One Night) |
| |||||||||||||
| Washout (Up to 1 Week) |
| |||||||||||||
| Intervention 2 (One Night) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All participants enrolled in this study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Pleural Pressure (Pes) | Pleural pressure (Pes) in mmHg monitored using an esophageal catheter. | Participants with upper airway obstruction (apneas, hypopneas, and flow limitation) during the Baseline sleep study, who had pleural pressure and blood pressure data collected during both Baseline and CPAP sleep studies. | Posted | Mean | Standard Deviation | mmHg | Overnight on both CPAP and No CPAP nights |
|
Over the two night sessions.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Baseline Sleep Study | Baseline sleep polysomnography involved the monitoring of electroencephalogram, electromyogram, electrocardiogram, airflow, heart rate, blood pressure, and pleural pressure during sleep with no CPAP. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mudiaga Sowho | Johns Hopkins University | 4105506264 | msowho1@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 16, 2019 | Nov 27, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D012891 | Sleep Apnea Syndromes |
| D012913 | Snoring |
| ID | Term |
|---|---|
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D020919 | Sleep Disorders, Intrinsic |
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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.
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| 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 |
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| NOT COMPLETED |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Participants will be treated with continuous positive airway pressure to relieve sleep-disordered breathing. 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 | Mean Arterial Blood Pressure (MAP) | Continuous blood pressure monitored using a non-invasive finger cuff. Data captured in mmHg. | Participants with upper airway obstruction (apneas, hypopneas, and flow limitation) during the Baseline sleep study, who had pleural pressure and blood pressure data collected during both Baseline and CPAP sleep studies. | Posted | Mean | Standard Deviation | mmHg | Overnight on both Baseline and CPAP studies |
|
|
|
| Secondary | 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. | Participants with adequate sleep time (>2hrs) on both Baseline and CPAP studies and AI measurements after both Baseline and CPAP studies. | Posted | Mean | Standard Error | percentage of pulse pressure | 15 minutes in the morning post Baseline and CPAP studies |
|
|
|
| Secondary | 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. | Participants with adequate sleep time (>2hrs) on both Baseline and CPAP studies and morning RHI measurements after both Baseline and CPAP studies. | Posted | Mean | Standard Error | score on a scale | 15 minutes |
|
|
|
| 0 |
| 30 |
| 0 |
| 30 |
| 0 |
| 30 |
| EG001 | CPAP Sleep Study | Participants were treated with continuous positive airway pressure (CPAP) on a separate night. Room air at pressures between 6-9 centimeters of water (cmH2O) were delivered via heated humidified tubing and a nasal mask. | 0 | 31 | 0 | 31 | 0 | 31 |
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| D020920 |
| Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D012135 | Respiratory Sounds |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |