Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
Primary Purpose
Marfan Syndrome
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Atenolol
Losartan
Sponsored by
About this trial
This is an interventional treatment trial for Marfan Syndrome focused on measuring Marfan syndrome, Losartan, Atenolol, Diastolic Function, Aortic Stiffness
Eligibility Criteria
Inclusion Criteria:
- Age greater than 25 years
- Clinical Marfan Syndrome
Exclusion Criteria:
- Previous aortic or cardiac surgery
- Pregnancy
- Renal Insufficiency
- Medication intolerance
Sites / Locations
- Brigham and Women's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Subjects Randomized to Losartan
Subjects Randomized to Atenolol
Arm Description
Losartan: 100 mg PO QD
Atenolol: 50 mg PO QD
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT00723801
First Posted
July 25, 2008
Last Updated
September 8, 2014
Sponsor
Brigham and Women's Hospital
Collaborators
Boston Children's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT00723801
Brief Title
Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
Official Title
Effects of Losartan vs Atenolol on Aortic Stiffness and Diastolic Function in Adults With Marfan Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
October 2007 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
Boston Children's Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
Please See Summary.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Marfan Syndrome
Keywords
Marfan syndrome, Losartan, Atenolol, Diastolic Function, Aortic Stiffness
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Subjects Randomized to Losartan
Arm Type
Active Comparator
Arm Description
Losartan: 100 mg PO QD
Arm Title
Subjects Randomized to Atenolol
Arm Type
Active Comparator
Arm Description
Atenolol: 50 mg PO QD
Intervention Type
Drug
Intervention Name(s)
Atenolol
Other Intervention Name(s)
Tenormin
Intervention Description
Atenolol 50mg PO QD
Intervention Type
Drug
Intervention Name(s)
Losartan
Other Intervention Name(s)
Cozaar
Intervention Description
Losartan 100mg PO QD
Primary Outcome Measure Information:
Title
Aortic Biophysical Properties - Pulse Wave Velocity
Description
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.
Time Frame
Baseline and 6 months
Secondary Outcome Measure Information:
Title
Diastolic Function - Ejection Fraction
Description
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.
Time Frame
Baseline and 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age greater than 25 years
Clinical Marfan Syndrome
Exclusion Criteria:
Previous aortic or cardiac surgery
Pregnancy
Renal Insufficiency
Medication intolerance
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark A Creager, MD
Organizational Affiliation
Brigham and Women;s Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
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