The Effect of Losartan in Bicuspid Aortic Valve Patients

Study Overview
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Brief Summary
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The specific aims of this study are to: Establish baseline levels of circulating MMP-2 and -9 , TIMP-1and- 2 and TGFB levels in individuals with bicuspid aortic valve and ascending aortic or aortic sinus measurements >40mm. Assess the effect on MMP levels during treatment with losartan, an angiotensin II receptor blocking agent. In the setting of losartan therapy for one year, evaluate the response of MMP levels in these patients, and clinical outcomes including effects on aortic growth rate

Official Title
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The Effect of Losartan Treatment on Matrix Metalloproteinase Levels and Outcomes in Bicuspid Aortic Valve Patients

Conditions
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Bicuspid Aortic Valve, Thoracic Aortic Aneurysm

Intervention / Treatment
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* Drug: Cozaar


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults >age 18 years and < 65 years old Able to give informed consent Presence of a bicuspid aortic valve (functional or true bicommisural)and ascending aorta or sinus of Valsalva >4.0cm No contraindications to treatment with Losartan, an Angiotensin II receptor blocker Able to safely participate in a 4 week drug washout period if currently taking an angiotensin II receptor blocker or ACE inhibitor. Exclusion Criteria: Unable to safely take losartan due to one or more of the following: Hypersensitivity to losartan or other angiotensin receptor blockers Pregnancy Nursing mothers History of angioedema Hypotension - chronically volume depleted patients Hepatic or renal impairment (Cr>1.5mg/dL) Hyperkalemia (K+>4.8) Renal artery stenosis Severe congestive heart failure (class III-IV) Currently taking potassium supplements or salt substitutes containing potassium Currently taking lithium Prior surgical intervention to aorta or aortic valve Unable or unwilling to give informed consent and follow up with study activities Currently taking an angiotensin receptor blocker or ACE inhibitor specifically for hypertension and are therefore unable to or are unwilling to participate in a 4 week drug washout period. Females of child bearing who are unwilling to practice adequate birth control throughout the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Losartan<br> | Drug: Cozaar<br>* Angiotensin II Receptor Blocker<br>* Other names: Losartan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory Markers Levels | Changes in levels of Matrix Metalloproteinase (MMP-2, MMP-9), Tissue Inhibitor of Metalloproteinases (TIMP 1, TIMP 2), & Transforming Growth Factor-Beta (TGFB) in circulation while taking medication from baseline at 3 months, 6 months and 12 months. The 12 month levels were the primary outcome. | Baseline and 12 months |