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

This study has been completed.
Sponsor:
Collaborator:
Children's Hospital Boston
Information provided by (Responsible Party):
Mark Alan Creager, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00723801
First received: July 25, 2008
Last updated: February 4, 2013
Last verified: February 2013

July 25, 2008
February 4, 2013
October 2007
December 2012   (final data collection date for primary outcome measure)
Aortic biophysical properties [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00723801 on ClinicalTrials.gov Archive Site
Diastolic Function [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
Effects of Losartan vs Atenolol on Aortic Stiffness and Diastolic Function in Adults With Marfan Syndrome

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.

Please See Summary.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Marfan Syndrome
  • Drug: Atenolol
    Atenolol 50mg PO QD
    Other Name: Tenormin
  • Drug: Losartan
    Losartan 100mg PO QD
    Other Name: Cozaar
  • Active Comparator: 1
    Atenolol
    Intervention: Drug: Atenolol
  • Experimental: 2
    Losartan
    Intervention: Drug: Losartan
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
39
December 2012
December 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age greater than 25 years
  • Clinical Marfan Syndrome

Exclusion Criteria:

  • Previous aortic or cardiac surgery
  • Pregnancy
  • Renal Insufficiency
  • Medication intolerance
Both
25 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00723801
2007p-001762
Yes
Mark Alan Creager, MD, Brigham and Women's Hospital
Brigham and Women's Hospital
Children's Hospital Boston
Principal Investigator: Mark A Creager, MD Brigham and Women;s Hospital
Brigham and Women's Hospital
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP