Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00723801
Other study ID # 2007p-001762
Secondary ID
Status Completed
Phase Phase 3
First received July 25, 2008
Last updated September 8, 2014
Start date October 2007
Est. completion date December 2012

Study information

Verified date September 2014
Source Brigham and Women's Hospital
Contact n/a
Is FDA regulated No
Health authority United States: Institutional Review Board
Study type Interventional

Clinical Trial 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.


Description:

Please See Summary.


Recruitment information / eligibility

Status Completed
Enrollment 40
Est. completion date December 2012
Est. primary completion date December 2012
Accepts healthy volunteers No
Gender Both
Age group 25 Years and older
Eligibility Inclusion Criteria:

- Age greater than 25 years

- Clinical Marfan Syndrome

Exclusion Criteria:

- Previous aortic or cardiac surgery

- Pregnancy

- Renal Insufficiency

- Medication intolerance

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Atenolol
Atenolol 50mg PO QD
Losartan
Losartan 100mg PO QD

Locations

Country Name City State
United States Brigham and Women's Hospital Boston Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
Brigham and Women's Hospital Children's Hospital Boston

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Aortic Biophysical Properties - Pulse Wave Velocity 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. Baseline and 6 months No
Secondary Diastolic Function - Ejection Fraction 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. Baseline and 6 months No
See also
  Status Clinical Trial Phase
Terminated NCT00763893 - Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome Phase 3
Recruiting NCT05809323 - Marfan Syndrome Moderate Exercise Trial II N/A
Completed NCT04776668 - Living With Marfan Syndrome and Your Aorta
Recruiting NCT01949233 - The Oxford Marfan Trial Phase 2
Active, not recruiting NCT01145612 - Atenolol Versus Losartan in the Prevention of Progressive Dilation of the Aorta in Marfan Syndrome Phase 3
Completed NCT04641325 - Marfan Syndrome Moderate Exercise Pilot N/A
Recruiting NCT06257004 - Genome-wide Epistasis for Cardiovascular Severity in Marfan Study
Completed NCT01322165 - National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions N/A
Recruiting NCT05700175 - Transcriptomic Study of Adult Population With Marfan Syndrome
Completed NCT00782327 - Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With Beta-blockers Phase 3
Not yet recruiting NCT05838235 - Adapted Physical Activity Program (APA) for Effort Rehabilitation of Children and Teenagers With Marfan Syndrome N/A
Recruiting NCT02148900 - Development of a Blood Test for Marfan Syndrome N/A
Active, not recruiting NCT05980104 - Single-Session "Empowered Relief" Class for Marfan Syndrome and Related Conditions N/A
Recruiting NCT02050113 - Complex Aortic Aneurysm Repair Using Physician Modified Endografts and Custom Made Devices N/A
Completed NCT00001641 - Study of Heritable Connective Tissue Disorders N/A
Completed NCT01715207 - Comparison Study of the Effect of Aliskiren Versus Negative Controls on Aortic Stiffness in Patients With Marfan Syndrome Under Treatment With Atenolol Phase 3
Completed NCT05516043 - Safety and Performance of POLYTHESE® Vascular Prosthesis
Recruiting NCT04776681 - Living With Marfans and Your Aorta: Surgical Outcomes Study
Completed NCT03236571 - Cardiorespiratory and Muscular Rehabilitation of Children and Young Adults With Marfan Syndrome. N/A
Recruiting NCT00683124 - Nebivolol Versus Losartan Versus Nebivolol+Losartan Against Aortic Root Dilation in Genotyped Marfan Patients Phase 3