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

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ClinicalTrials.gov Identifier: NCT00723801
Recruitment Status : Completed
First Posted : July 29, 2008
Results First Posted : September 1, 2014
Last Update Posted : September 9, 2014
Boston Children's Hospital
Information provided by (Responsible Party):
Mark Alan Creager, MD, Brigham and Women's Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Marfan Syndrome Drug: Atenolol Drug: Losartan Phase 3

Detailed Description:
Please See Summary.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Losartan vs Atenolol on Aortic Stiffness and Diastolic Function in Adults With Marfan Syndrome
Study Start Date : October 2007
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Marfan Syndrome

Arm Intervention/treatment
Active Comparator: Subjects Randomized to Losartan
Losartan: 100 mg PO QD
Drug: Losartan
Losartan 100mg PO QD
Other Name: Cozaar

Active Comparator: Subjects Randomized to Atenolol
Atenolol: 50 mg PO QD
Drug: Atenolol
Atenolol 50mg PO QD
Other Name: Tenormin

Primary Outcome Measures :
  1. Aortic Biophysical Properties - Pulse Wave Velocity [ Time Frame: Baseline and 6 months ]
    Aortic stiffness was assessed using applanation tonometry (SphygmoCor®, AtCor Medical, West Ryde, NSW, Sydney, Australia) to measure carotid to femoral artery pulse wave velocity (PWV). With the patient lying supine in a quiet environment, a handheld micromanometer-tipped probe was applied to the skin surface over the carotid and femoral arteries, compressing the vessel wall so that transmural forces within the vessel wall were perpendicular to the arterial surface. The distance from the sternal notch to the sites of carotid and femoral pulse acquisition were measured and inputted into the device to represent the relative distance from the carotid to femoral artery. The calculation of distance divided by time of pulse upstroke relative to the upstroke of the QRS on a 3 lead surface EKG was used by the device to calculate velocity. All recorded measurements met the manufacturer's quality control standards integrated into the software package.

Secondary Outcome Measures :
  1. Diastolic Function - Ejection Fraction [ Time Frame: Baseline and 6 months ]
    Two-dimensional echocardiography was performed using a 3.0 MHz transducer (General Electric VIVID 7). Left ventricular and left atrial dimensions were determined in parasternal long axis views. Left ventricular ejection fraction was calculated using the modified Simpsons calculation in the apical two and four chamber views.

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Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age greater than 25 years
  • Clinical Marfan Syndrome

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00723801

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United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Boston Children's Hospital
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Principal Investigator: Mark A Creager, MD Brigham and Women;s Hospital
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Responsible Party: Mark Alan Creager, MD, Principal Investigator, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00723801    
Other Study ID Numbers: 2007p-001762
First Posted: July 29, 2008    Key Record Dates
Results First Posted: September 1, 2014
Last Update Posted: September 9, 2014
Last Verified: September 2014
Keywords provided by Mark Alan Creager, MD, Brigham and Women's Hospital:
Marfan syndrome
Diastolic Function
Aortic Stiffness
Additional relevant MeSH terms:
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Marfan Syndrome
Pathologic Processes
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Connective Tissue Diseases
Limb Deformities, Congenital
Musculoskeletal Abnormalities
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists