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

This study has been completed.
Children's Hospital Boston
Information provided by (Responsible Party):
Mark Alan Creager, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
First received: July 25, 2008
Last updated: September 8, 2014
Last verified: September 2014

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 Intervention Phase
Marfan Syndrome
Drug: Atenolol
Drug: Losartan
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Losartan vs Atenolol on Aortic Stiffness and Diastolic Function in Adults With Marfan Syndrome

Resource links provided by NLM:

Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • Aortic Biophysical Properties - Pulse Wave Velocity [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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:
  • Diastolic Function - Ejection Fraction [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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.

Enrollment: 40
Study Start Date: October 2007
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:
Please See Summary.

Ages Eligible for Study:   25 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00723801

United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Children's Hospital Boston
Principal Investigator: Mark A Creager, MD Brigham and Women;s Hospital
  More Information

Responsible Party: Mark Alan Creager, MD, Principal Investigator, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00723801     History of Changes
Other Study ID Numbers: 2007p-001762 
Study First Received: July 25, 2008
Results First Received: August 15, 2014
Last Updated: September 8, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
Marfan syndrome
Diastolic Function
Aortic Stiffness

Additional relevant MeSH terms:
Marfan Syndrome
Abnormalities, Multiple
Bone Diseases
Bone Diseases, Developmental
Cardiovascular Abnormalities
Cardiovascular Diseases
Congenital Abnormalities
Connective Tissue Diseases
Genetic Diseases, Inborn
Heart Defects, Congenital
Heart Diseases
Limb Deformities, Congenital
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Pathologic Processes
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 26, 2016