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

This study is currently recruiting participants. (see Contacts and Locations)

Verified May 2015 by Baylor College of Medicine

Sponsor:

Collaborator:

National Heart, Lung, and Blood Institute (NHLBI)

Information provided by (Responsible Party):

Zeenat Safdar, Baylor College of Medicine

ClinicalTrials.gov Identifier:

NCT01468571

First received: November 3, 2011

Last updated: May 6, 2015

Last verified: May 2015

History of Changes

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:

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: Potassium Pulmonary Hypertension

Drug Information available for: Spironolactone

Genetic and Rare Diseases Information Center resources: Pulmonary Arterial Hypertension Dextrocardia

U.S. FDA Resources

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 (Adult, Senior)
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

National Heart, Lung, and Blood Institute (NHLBI)

Investigators


Principal Investigator:	Zeenat Safdar, MD	Baylor College of Medicine

More Information


Responsible Party:	Zeenat Safdar, Associate 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:	May 6, 2015
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 Hypertension, Pulmonary Familial Primary Pulmonary Hypertension Vascular Diseases Cardiovascular Diseases Lung Diseases Respiratory Tract Diseases Spironolactone	Mineralocorticoid Receptor Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Diuretics, Potassium Sparing Diuretics Natriuretic Agents

ClinicalTrials.gov processed this record on September 30, 2016

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