Marfan SyndromePhase 3NCT00723801
Effects of Losartan Versus Atenolol on Aortic and Cardiac Muscle Stiffness in Adults With Marfan Syndrome
A Phase 3 study testing Atenolol and Losartan in people with Marfan Syndrome, run by Brigham and Women's Hospital at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 25 years and older
- Conditions the study is for
- Marfan Syndrome
- What is being tested?
- Atenolol and Losartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2007to Dec 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age greater than 25 years
- Clinical Marfan Syndrome
Who cannot join
- Previous aortic or cardiac surgery
- Pregnancy
- Renal Insufficiency
- Medication intolerance
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: 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.
Read the detailed description
Please See Summary.
- Conditions
- Marfan Syndrome
- Being tested
- Atenolol, Losartan
- Keywords
- Marfan syndrome, Losartan, Atenolol, Diastolic Function, Aortic Stiffness
- Medical subject headings
- Marfan Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtenololDrug
Also called Tenormin
Atenolol 50mg PO QD
LosartanDrug
Also called Cozaar
Losartan 100mg PO QD
| Study group | Role | What they receive |
|---|---|---|
| Subjects Randomized to Losartan | Active comparator | Losartan: 100 mg PO QD Receives: Drug: Losartan |
| Subjects Randomized to Atenolol | Active comparator | Atenolol: 50 mg PO QD Receives: Drug: Atenolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 6 months
Secondary outcomes (1)
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.
Measured: Baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2008 (estimated)
- Study startOct 2007
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Marfan SyndromeStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Boston Children's Hospital
- Responsible party
- Principal investigator, Mark Alan Creager, MD, Brigham and Women's Hospital
- Investigators
- Mark A Creager, MD, Principal investigator, Brigham and Women;s Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00723801
- Sponsor's protocol ID
- 2007p-001762
- Status last verified
- Sep 2014
- First submitted
- 25 Jul 2008
- Last updated
- 9 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Losartan vs Atenolol on Aortic Stiffness and Diastolic Function in Adults With Marfan Syndrome
- ClinicalTrials.gov ID
- NCT00723801
- Acronym / sponsor ID
- 2007p-001762
- Conditions
- Marfan Syndrome
- Keywords
- Marfan syndrome, Losartan, Atenolol, Diastolic Function, Aortic Stiffness
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Boston Children's Hospital
- Study start
- Oct 2007
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 29 Jul 2008 (estimated)
- Results
- Posted 1 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Please See Summary.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subjects Randomized to Losartan | Active comparator | Drug: LosartanLosartan: 100 mg PO QD |
| Subjects Randomized to Atenolol | Active comparator | Drug: AtenololAtenolol: 50 mg PO QD |
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age greater than 25 years
- Clinical Marfan Syndrome
Key exclusion criteria (4 listed)
- Previous aortic or cardiac surgery
- Pregnancy
- Renal Insufficiency
- Medication intolerance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtenololAlso: TenorminAtenolol 50mg PO QD | Drug | Subjects Randomized to Atenolol |
| LosartanAlso: CozaarLosartan 100mg PO QD | Drug | Subjects Randomized to Losartan |
Primary outcome
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.
1 secondary outcome
Diastolic Function - Ejection Fraction
Time frame: Baseline and 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Marfan Syndrome
RecruitingObservational study
Asprosin and miRNA Expression in Young Women With Metabolic Syndrome
Metabolic Syndrome, Insulin Resistance
Enrolling by invitationObservational study
Advanced Ultrasound Signal Processing of Suspicious Breast Images
Breast Cancer, Breast Cyst
RecruitingObservational study
Pregnancy in Women With Rare Multisystemic Vascular Diseases: COGRare5 Study
Vascular Anomaly, Osler Rendu Disease
Not yet recruitingObservational study
Asprosin in Behect Patients
Behcet Disease
Not yet recruitingObservational study
Serum Asprosin, Metabolic Syndrome, and Cardiometabolic Risk in Rheumatoid Arthritis
Rheumatoid Arthritis, Metabolic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark A Creager, MD principal investigator
Brigham and Women;s Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Atenolol and Losartan in people with Marfan Syndrome, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Aortic Biophysical Properties - Pulse Wave Velocity (time frame: Baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2014.