Clinical Trial: Losartan Versus Atenolol for the Treatment of Marfan Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized Double-blind Study Assessing the Effects of Losartan Versus Atenolol on Pulse Wave Velocity and the Biophysical Properties of the Aorta in Patients With Marfan Syndr

Brief Summary: Marfan syndrome is a genetic disease of our connective tissue, which provides material and support for our skeleton, muscles, blood vessels and other parts of our bodies. People with Marfan syndrome may be tall and thin with slender, tapering fingers, long arms and legs, and spine curvature. They often have heart and eye problems. In some patients, the condition is very mild and the person has few or no symptoms. Others are always at risk of life-threatening problems, which usually involve damage to the valves in the heart or weakening of the large blood vessels leading from the heart. If the blood vessels become weak, they can balloon out (dilate) and break (rupture), which might cause the person to die suddenly. We have only a limited ability to stop the progression of disease in Marfan syndrome. Typically we use medicines that lower heart rate or blood pressure (or both). But this does not prevent the disease and very few drugs work well enough to keep patients from needing surgery or dying suddenly because a blood vessel has torn open. Our objective is to study two medicines to see if one, or both, can improve blood vessel function in patients with Marfan syndrome. One (Atenolol) belongs to a group of drugs called beta blockers and is often used to treat high blood pressure. It is the most common drug that is currently used to treat patients with Marfan syndrome. The other (Losartan) is also used for high blood pressure, but works in a different way. This study will help us to find better ways to treat people who have Marfan syndrome and to identify early changes in blood vessel function that may help to prevent long-term complications.

Detailed Summary:

The objective of the proposed research is to conduct a randomized, double-blind superiority feasibility study to compare the effects of two types of medication (Losartan, an Angiotensin Receptor Blocker, and Atenolol, a beta blocker) on vascular function in patients with Marfan syndrome (MFS). Our outcomes will include measuring the pulse wave velocity (PWV) and other biophysical properties of the aorta in the two groups of patients. This study will provide essential pilot data and development of logistics to enable a full multi-centre randomized controlled trial to test the hypothesis that Losartan will improve vascular function and, in the long-term, slow the rate of aortic root dilation.

MFS is an inherited disorder that affects 1:5000 of the population (i.e., 6000 people) in Canada alone. In MFS, mutations in the FBN1 gene lead to production of abnormal fibrillin 1 and to connective tissue abnormalities that impair skeletal, ocular, pulmonary and, most importantly, cardiovascular systems. Cardiovascular complications are also related to endothelial dysfunction, which has widespread implications for the health of large and muscular blood vessels and has effects on blood pressure, thrombosis, cholesterol levels and general vascular homeostasis. In MFS, progressive dilation, dissection and rupture of the aortic root may occur. This dilation is not solely due to the primary abnormality in collagen caused by the abnormal fibrillin protein. It remains unclear what the vascular mechanisms are that cause dilation of the aortic root. Eventual aortic rupture is a major cause of sudden death in MFS. If untreated, MFS significantly shortens the lifespan of affected individuals: half will succumb in their late 20s or early 30s, usually of aortic rupture. As such, it is crucial to develop effective treatments for cardiovascular disease in MFS and to improve our ability to detect cr
Sponsor: University of British Columbia

Current Primary Outcome: Pulse Wave Velocity [ Time Frame: 12 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Biophysical properties of the aorta [ Time Frame: 12 months ]
  • Brachial artery reactivity [ Time Frame: 12 months ]
  • Aortic root dimension and area [ Time Frame: 12 months ]


Original Secondary Outcome: Same as current

Information By: University of British Columbia

Dates:
Date Received: January 3, 2008
Date Started: January 2008
Date Completion:
Last Updated: July 11, 2012
Last Verified: July 2012