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

Baylor College of Medicine

Status and phase: Unknown; Phase 4

Conditions: Pulmonary Hypertension

Treatments: Drug: Spironolactone; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01468571

K23HL093214 (U.S. NIH Grant/Contract)

H24178

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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50 participants in 2 patient groups

Spironolactone

Experimental group

Description:

Drug: Spironolactone Drug: Placebo

Treatment:

Drug: Spironolactone

Placebo

Experimental group

Description:

Drug: Placebo Drug: Spironolactone

Treatment:

Drug: Placebo