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

Pulmonary Hypertension Clinical Trial

Official title:

Effects of Spironolactone on Collagen Metabolism in Pulmonary Arterial Hypertension

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01468571
• Other study ID #: H24178
• Secondary ID: K23HL093214
• Status: Recruiting
• Phase: Phase 4
• First received: November 3, 2011
• Last updated: May 6, 2015
• Start date: July 2011
• Est. completion date: December 2015

Study information

• Verified date: May 2015
• Source: Baylor College of Medicine
• Contact: Zeenat Safdar, MD
• Phone: 713-798-2400
• Email: safdar[@]bcm.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Baylor College of Medicine	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in biomarker levels in the spironolactone treated as compared to placebo treated group.	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.	16 week	No
Secondary	Number of adverse events in patients treated with spironolactone as compared to placebo.	Safety and tolerability of spironolactone as compared to placebo in PAH.	16 week	Yes
Secondary	Change in six-minute walk distance from baseline to week 8 and week 16.		16 week	No
Secondary	Composite end-point	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.	16 week	No