Comparison Study of the Effect of Aliskiren Versus Negative Controls on Aortic Stiffness in Patients With Marfan Syndrome Under Treatment With Atenolol

Marfan Syndrome Clinical Trial

Official title:

Comparison Study of the Effect of Aliskiren Versus Negative Controls on Aortic Stiffness in Patients With Marfan Syndrome Under Treatment With Atenolol

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01715207
• Other study ID #: 2009-10-025
• Status: Completed
• Phase: Phase 3
• First received: October 24, 2012
• Last updated: November 20, 2016
• Start date: June 2010
• Est. completion date: December 2014

Study information

• Verified date: November 2016
• Source: Samsung Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: December 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Marfan Syndrome
• Syndrome

Intervention

Drug:
• Aliskiren

• Atenolol

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Central aortic PWV(pulsed wave velocity)		6 months	No
Secondary	Central aortic distensibility by MRI at week 24		6 months	No