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| Name | Class |
|---|---|
| Boston Children's Hospital | OTHER |
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Marfan syndrome is an inherited connective tissue disorder with morbidity and mortality from aortic dilation and dissection. The degree of aortic dilation and response to beta-blockade (standard of care) vary in adults with Marfan syndrome. However, aortic stiffness is often present, and can be a predictor of aortic dilation and cardiovascular complications. In addition, adults with Marfan syndrome develop left ventricular diastolic dysfunction, which can progress to heart failure. Aortic stiffness and diastolic dysfunction are important and logical therapeutic targets in adults with Marfan syndrome.
TGF-beta mediates disease pathogenesis in Marfan syndrome and contributes to aortic stiffness. The angiotensin receptor blocker, losartan, inhibits TGF-beta activity and reverses aortic wall pathology in a Marfan mouse model. Losartan also decreases aortic stiffness and improves diastolic function in hypertension, renal disease and hypertrophic cardiomyopathy.
This trial is a randomized, double-blind trial of 50 adults with Marfan syndrome, treated with 6 months of atenolol vs. losartan. Arterial tonometry for aortic stiffness and echocardiography for diastolic function will be performed at the beginning and end of treatment. A blood draw for serum markers of extracellular matrix turnover and inflammation will also be performed at 0 and 6 months. We plan to determine whether losartan decreases aortic stiffness and left ventricular diastolic dysfunction significantly more than atenolol.
Please See Summary.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subjects Randomized to Losartan | Active Comparator | Losartan: 100 mg PO QD |
|
| Subjects Randomized to Atenolol | Active Comparator | Atenolol: 50 mg PO QD |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atenolol | Drug | Atenolol 50mg PO QD |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Aortic Biophysical Properties - Pulse Wave Velocity | Aortic stiffness was assessed using applanation tonometry (SphygmoCor®, AtCor Medical, West Ryde, NSW, Sydney, Australia) to measure carotid to femoral artery pulse wave velocity (PWV). With the patient lying supine in a quiet environment, a handheld micromanometer-tipped probe was applied to the skin surface over the carotid and femoral arteries, compressing the vessel wall so that transmural forces within the vessel wall were perpendicular to the arterial surface. The distance from the sternal notch to the sites of carotid and femoral pulse acquisition were measured and inputted into the device to represent the relative distance from the carotid to femoral artery. The calculation of distance divided by time of pulse upstroke relative to the upstroke of the QRS on a 3 lead surface EKG was used by the device to calculate velocity. All recorded measurements met the manufacturer's quality control standards integrated into the software package. | Baseline and 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Diastolic Function - Ejection Fraction | Two-dimensional echocardiography was performed using a 3.0 MHz transducer (General Electric VIVID 7). Left ventricular and left atrial dimensions were determined in parasternal long axis views. Left ventricular ejection fraction was calculated using the modified Simpsons calculation in the apical two and four chamber views. | Baseline and 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark A Creager, MD | Brigham and Women;s Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Subjects Randomized to Atenolol | Atenolol: Atenolol 50mg PO QD |
| FG001 | Subjects Randomized to Losartan | Losartan: Losartan 100mg PO QD |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Subjects Randomized to Atenolol | Atenolol: Atenolol 50mg PO QD |
| BG001 | Subjects Randomized to Losartan | Losartan: Losartan 100mg PO QD |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Aortic Biophysical Properties - Pulse Wave Velocity | Aortic stiffness was assessed using applanation tonometry (SphygmoCor®, AtCor Medical, West Ryde, NSW, Sydney, Australia) to measure carotid to femoral artery pulse wave velocity (PWV). With the patient lying supine in a quiet environment, a handheld micromanometer-tipped probe was applied to the skin surface over the carotid and femoral arteries, compressing the vessel wall so that transmural forces within the vessel wall were perpendicular to the arterial surface. The distance from the sternal notch to the sites of carotid and femoral pulse acquisition were measured and inputted into the device to represent the relative distance from the carotid to femoral artery. The calculation of distance divided by time of pulse upstroke relative to the upstroke of the QRS on a 3 lead surface EKG was used by the device to calculate velocity. All recorded measurements met the manufacturer's quality control standards integrated into the software package. | Posted | Mean | Standard Deviation | change in meters/second | Baseline and 6 months |
|
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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 | Subjects Randomized to Atenolol | Atenolol: Atenolol 50mg PO QD |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mark Creager | Brigham and Women's Hospital | 617-732-5267 | mcreager@partners.org |
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| ID | Term |
|---|---|
| D008382 | Marfan Syndrome |
| ID | Term |
|---|---|
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D006330 | Heart Defects, Congenital |
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| ID | Term |
|---|---|
| D001262 | Atenolol |
| D019808 | Losartan |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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| Losartan | Drug | Losartan 100mg PO QD |
|
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Pulse wave velocity | Pulse Wave Velocity is a measure of arterial stiffness that is a well-characterized indicator of cardiovascular risk. | Mean | Standard Deviation | meters/second |
|
| Ejection Fraction | Ejection Fraction is a measurement of how much blood volume is ejected from the left ventricle with each contraction. It is a measure of how effectively the heart is pumping blood. | Mean | Standard Deviation | % |
|
| Subjects Randomized to Atenolol |
Atenolol: Atenolol 50mg PO QD |
| OG001 | Subjects Randomized to Losartan | Losartan: Losartan 100mg PO QD |
|
|
| Secondary | Diastolic Function - Ejection Fraction | Two-dimensional echocardiography was performed using a 3.0 MHz transducer (General Electric VIVID 7). Left ventricular and left atrial dimensions were determined in parasternal long axis views. Left ventricular ejection fraction was calculated using the modified Simpsons calculation in the apical two and four chamber views. | Posted | Mean | Standard Deviation | Change in % ejection fraction | Baseline and 6 months |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| EG001 | Subjects Randomized to Losartan | Losartan: Losartan 100mg PO QD | 0 | 20 | 0 | 20 |
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| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |