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

Mass General Brigham

Status and phase: Completed; Phase 3

Conditions: Marfan Syndrome

Treatments: Drug: Atenolol; Drug: Losartan

Study type: Interventional

Funder types: Other

Identifiers

NCT00723801

2007p-001762

Details and patient eligibility

About

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.

Full description

Please See Summary.

Enrollment: 40 patients

Sex: All

Ages: 25+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age greater than 25 years
• Clinical Marfan Syndrome

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 2 patient groups

Subjects Randomized to Losartan

Active Comparator group

Description:

Losartan: 100 mg PO QD

Treatment:

Drug: Losartan

Subjects Randomized to Atenolol

Active Comparator group

Description:

Atenolol: 50 mg PO QD

Treatment:

Drug: Atenolol