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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Baylor College of Medicine
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Zeenat Safdar, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01468571
First received: November 3, 2011
Last updated: February 4, 2013
Last verified: February 2013
  Purpose

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 Intervention Phase
Pulmonary Hypertension
Drug: Spironolactone
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Spironolactone on Collagen Metabolism in Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Change in biomarker levels in the spironolactone treated as compared to placebo treated group. [ Time Frame: 16 week ] [ Designated as safety issue: No ]
    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:
  • Number of adverse events in patients treated with spironolactone as compared to placebo. [ Time Frame: 16 week ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
  • Composite end-point [ Time Frame: 16 week ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 50
Study Start Date: July 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01468571

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

Locations
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Zeenat Safdar, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Zeenat Safdar, Assistant Professor of Medicine, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01468571     History of Changes
Other Study ID Numbers: H24178, K23HL093214
Study First Received: November 3, 2011
Last Updated: February 4, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
Potassium Sparing Diuretics
Right-sided heart failure
Edema

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Spironolactone
Sodium Channel Blockers
Aldosterone Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014