NCT00723801

Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome

Effects of Losartan vs Atenolol on Aortic Stiffness and Diastolic Function in Adults With Marfan Syndrome

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 25 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Marfan Syndrome

Interventions

Type	Name	Description
DRUG	Atenolol	Atenolol 50mg PO QD
DRUG	Losartan	Losartan 100mg PO QD

Timeline

• Start date: 2007-10-01
• Primary completion: 2012-12-01
• Completion: 2012-12-01
• First posted: 2008-07-29
• Last updated: 2014-09-09
• Results posted: 2014-09-01

Locations

1 site across 1 country: United States