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

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ClinicalTrials.gov Identifier: NCT01468571
Recruitment Status : Unknown
Verified May 2015 by Zeenat Safdar, Baylor College of Medicine.
Recruitment status was:  Recruiting
First Posted : November 9, 2011
Last Update Posted : May 8, 2015
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Zeenat Safdar, Baylor College of Medicine

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.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Drug: Spironolactone Drug: Placebo Phase 4

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Spironolactone on Collagen Metabolism in Pulmonary Arterial Hypertension
Study Start Date : July 2011
Estimated Primary Completion Date : July 2015
Estimated Study Completion Date : December 2015

Arm Intervention/treatment
Experimental: Spironolactone
Drug: Spironolactone Drug: Placebo
Drug: Spironolactone
50 mg po daily of spironolactone for 8 weeks. A cross-over study where each subject will receive spironolactone or placebo in a random order for 8 weeks each.
Other Name: Aldactone

Experimental: Placebo
Drug: Placebo Drug: Spironolactone
Drug: Placebo

Each subject will receive placebo or spironolactone for 8 weeks. At the end of week 8, treatment arm for each subject will be blindly switched.

So if a study patient received placebo for the first 8 weeks then he/she will be switched to receive active drug (spironolactone) for the next 8 weeks.

Other Name: sugar pill

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. Change in six-minute walk distance from baseline to week 8 and week 16. [ Time Frame: 16 week ]
  3. 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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age 18 years or older
  • Body weight > 40 kg
  • PAH Diagnostic Group I
  • Stable subjects with no change in PAH specific therapy within the last 4 weeks
  • No change in dose of background therapy (digoxin, diuretic) within the last 2 weeks excluding anticoagulation

Exclusion Criteria:

  • Unable to give informed consent
  • Hemodynamically unstable subjects
  • Pregnant or breast feeding
  • Have significant renal insufficiency (serum creatinine >2.5 mg per deciliter or required hemodialysis)
  • Have significant liver dysfunction (AST or ALT more than three times upper limit of normal)
  • Currently on aldosterone receptor blocker (spironolactone or eplerenone) or ACE inhibitor
  • PH due to left heart disease
  • Unable or unwilling to comply with study procedures

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01468571

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Contact: Zeenat Safdar, MD 713-798-2400 safdar@bcm.edu
Contact: Gwendolyn Goodloe 713-798-2400 gmb@bcm.edu

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United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: Zeenat Safdar, MD Baylor College of Medicine
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Responsible Party: Zeenat Safdar, Associate Professor of Medicine, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01468571    
Other Study ID Numbers: H24178
K23HL093214 ( U.S. NIH Grant/Contract )
First Posted: November 9, 2011    Key Record Dates
Last Update Posted: May 8, 2015
Last Verified: May 2015
Keywords provided by Zeenat Safdar, Baylor College of Medicine:
Potassium Sparing Diuretics
Right-sided heart failure
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Pulmonary Arterial Hypertension
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Natriuretic Agents