Marfan Syndrome | Comparison of Aliskiren vs Negative Controls on Aortic Stiffness in Patients With MFS

Marfan Syndrome research study

What is the primary objective of this study?

Marfan syndrome (MFS) is an inherited disorder of connective tissue with morbidity and mortality from aortic dilatation and dissection. The current standard of care is beta-blocker (BB) treatment and therapeutic target is heart rate. The degree of aortic dilatation and response to BB vary in adults with MFS. However, aortic stiffness is often present, and can be a predictor of aortic dilatation and cardiovascular complications. Aortic stiffness is a logical therapeutic target in adults with MFS. Transforming growth factor beta(TGF-beta) mediates disease pathogenesis in MFS and contributes to aortic stiffness. Cross-talk between TGF-beta system and renin-angiotensin system (RAS) has been demonstrated. The angiotensin receptor blocker (ARB), losartan, inhibits TGF-beta activity and reverses aortic wall pathology in a Marfan mouse model. In a small cohort study, the use of ARB therapy (losartan or irbesartan) significantly slowed the rate of progressive aortic dilatation in patients with MFS, after BB therapy had failed to prevent aortic root dilatation. In another study, angiotensin converting enzyme inhibitor, perindopril, reduced both aortic stiffness and aortic root diameter in patients with MFS taking standard BB therapy. Renin inhibitor, aliskiren, has not been studied to reduce aortic stiffness and attenuate aortic dilatation in patients with MFS. This trial is a randomized, open-label trial of 32 patients with Marfan syndrome, treated with 6 months of aliskiren vs. negative controls in patients with MFS under atenolol treatment. MRI for aortic pulsed wave velocity (PWV) and distensibility, measurements of central BP (CBP) and augmentation index (AIx) will be performed at the beginning and end of treatment. A blood drawn for serum markers of TGF-beta, extracellular matrix turnover and inflammation will also be performed at 0 and 6 months. We plan to determine whether aliskiren decreases aortic stiffness significantly more than negative controls in patients with MFS under atenolol treatment.

Who is eligible to participate?

Inclusion Criteria: 1. Diagnosis of MFS by Ghent criteria and/or genetically proven Fibrillin-1 (FBN1) mutation 2. Age between 14 and 55 years 3. Beta-blocker treatment at least 3 months 4. subjects must not have been receiving chronic RAS inhibitor therapy (i.e. ARBs, or ACE inhibitors)>= 90days prior to screening 5. Written informed consent from the patients or authorized representatives must be obtained Exclusion Criteria: 1. previous medical history of aortic surgery and/or dissection 2. significant valve disease requiring surgery 3. aortic root dimension > 5.5 cm 4. renal dysfunction (creatinine > upper normal limit) 5. pregnancy or planned pregnancy within 12 months of study entry or breast feeding women 6. Known renal artery stenosis 7. Hypersensitivity to the aliskiren or to any of the excipients 8. Elevation of serum creatinine during follow-up (> 30% than baseline) 9. Diarrhea, resulting severe dehydration 10. Development of gout or ureter stone 11. Symptomatic hypotension (SBP<90 with symptom) 12. Hyperkalemia 13. Concomitant use with ciclosporin A

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Marfan Syndrome

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.



Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Atenolol tablet and Aliskiren 150mg or 300mg tablet by mouth per day for 6month

AtenololAtenolol tablet(Negative controls, Open-label)

Study Status


Start Date: June 2010

Completed Date: December 2014

Phase: Phase 3

Type: Interventional


Primary Outcome: Central Aortic Distensibility by MRI

Secondary Outcome: Central Aortic PWV(Pulsed Wave Velocity)

Study sponsors, principal investigator, and references

Principal Investigator: Duk-Kyung Kim, PhD MD

Lead Sponsor: Samsung Medical Center


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