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

NCT ID: NCT01468571

Last Updated: 2015-05-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2015-12-31

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 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.

Conditions

Pulmonary Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Spironolactone

Drug: Spironolactone Drug: Placebo

Group Type: EXPERIMENTAL

Spironolactone

Intervention Type: DRUG

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.

Placebo

Drug: Placebo Drug: Spironolactone

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Aldactone; sugar pill

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Zeenat Safdar

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zeenat Safdar, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

Baylor College of Medicine

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Zeenat Safdar, MD

Role: CONTACT

safdar@bcm.edu

713-798-2400

Gwendolyn Goodloe

Role: CONTACT

gmb@bcm.edu

713-798-2400

Other Identifiers

K23HL093214

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H24178

Identifier Type: -

Identifier Source: org_study_id