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”

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.

Intervention(s) in this Clinical Trial

• Drug: Atenolol
  • Atenolol 50mg PO QD
• Drug: Losartan
  • Losartan 100mg PO QD

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Atenolol
• Experimental: 2
  • Losartan

Primary Measures

• Aortic biophysical properties
  • Time Frame: 6 months
    Safety Issue?: No

Secondary Measures

• Diastolic Function
  • Time Frame: 6 months
    Safety Issue?: No

Inclusion Criteria:

• Age greater than 25 years
• Clinical Marfan Syndrome

Exclusion Criteria:

• Previous aortic or cardiac surgery
• Pregnancy
• Renal Insufficiency
• Medication intolerance

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 25 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Brigham and Women's Hospital Other

Overall Clinical Trial Officials and Contacts

Mark A Creager, MD Principal Investigator Brigham and Women;s Hospital  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00723801

Study ID Number: 2007p-001762

ClinicalTrials.gov Identifier: NCT00723801

Health Authority: United States: Institutional Review Board