Comparison Study of the Effect of Aliskiren Versus Negative Controls on Aortic Stiffness in Patients With Marfan Syndrome Under Treatment With Atenolol
Information source: Samsung Medical Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Marfan Syndrome
Intervention: Aliskiren (Drug); Atenolol (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Samsung Medical Center Official(s) and/or principal investigator(s):
Duk-Kyung Kim, PhD MD, Principal Investigator, Affiliation: Samsung Medical Center
Overall contact:
Duk-Kyung Kim, PhD MD, Phone: 82-2-3410-3419, Email: dukkyung.kim@samsung.com
Summary
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.
Clinical Details
Official title: Comparison Study of the Effect of Aliskiren Versus Negative Controls on Aortic Stiffness in Patients With Marfan Syndrome Under Treatment With Atenolol
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Central aortic PWV(pulsed wave velocity)
Secondary outcome: Central aortic distensibility by MRI at week 24
Eligibility
Minimum age: 14 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
Duk-Kyung Kim, PhD MD, Phone: 82-2-3410-3419, Email: dukkyung.kim@samsung.com
Samsung Medical Center, Seoul 135-710, Korea, Republic of; Recruiting
Duk-Kyung Kim, PhD MD, Phone: 82-2-3410-3419, Email: dukkyung.kim@samsung.com
Sung-A Chang, PhD MD, Phone: 82-2-3410-3419, Email: elisabet.chang@gmail.com
Duk-Kyung Kim, PhD MD, Principal Investigator
Sung-A Chang, PhD MD, Sub-Investigator
Additional Information
Starting date: June 2010
Last updated: October 29, 2012
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