Clinical Trial: Effects of Spironolactone on Collagen Metabolism in Patients With Pulmonary Arterial Hypertension

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Effects of Spironolactone on Collagen Metabolism in Pulmonary Arterial Hypertension

Brief Summary: The purpose of this study is to determine the effects of spironolactone on collagen markers in a large number of patients with pulmonary hypertension. In addition, safety and tolerability of spironolactone, an aldosterone receptor antagonist, in patients with pulmonary arterial hypertension, will be determined.

Detailed Summary: Pulmonary arterial hypertension (PAH) is an orphan disease characterized by pulmonary artery hypertrophy, and resulting vascular remodeling of involved vessels, often leading to right heart failure. Accumulating evidence from vascular biology, animal models, and therapeutic drug trials suggests significant contributions of the neurohormonal milieu to the disease process, morbidity, and mortality. The renin-angiotensin-aldosterone system (RAAS) is an important neurohormonal pathway that induces collagen synthesis in the myocardium and systemic vasculature. There is paucity of data regarding the contribution of RAAS in the pathogenesis of PAH and the effects of aldosterone blockade in the amelioration of PAH. Thus, the overall goal of this proposal is to investigate the contribution of RAAS to the pathogenesis of PAH, and to explore the effects of an aldosterone blocker, spironolactone, in PAH.
Sponsor: Baylor College of Medicine

Current Primary Outcome: Change in biomarker levels in the spironolactone treated as compared to placebo treated group. [ Time Frame: 16 week ]

50 participants will be enrolled in a 16-week study, and each subject will receive placebo or active drug in a random order. At the end of week 8, treatment arm for each subject will be blindly switched. Biomarker levels will be drawn 3 times (baseline, week 8, and week 16) during the study period for each subject.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of adverse events in patients treated with spironolactone as compared to placebo. [ Time Frame: 16 week ]
    Safety and tolerability of spironolactone as compared to placebo in PAH.
  • Change in six-minute walk distance from baseline to week 8 and week 16. [ Time Frame: 16 week ]
  • Composite end-point [ Time Frame: 16 week ]
    Composite end-point predefined as greater than 10% increase in walk distance, improvement by at least one functional class and absence of clinical worsening. Clinical worsening will be defined as hospitalization for worsening PAH, all-cause death, addition of prostacyclin therapy, lung transplantation, or atrial septostomy.


Original Secondary Outcome: Same as current

Information By: Baylor College of Medicine

Dates:
Date Received: November 3, 2011
Date Started: July 2011
Date Completion: December 2015
Last Updated: May 6, 2015
Last Verified: May 2015