A Pilot Study of the Effect of Spironolactone Therapy on Exercise Capacity and Endothelial Dysfunction in Pulmonary Arterial Hypertension
National Institutes of Health Clinical Center (CC)
Summary
Background: \- High blood pressure in the lungs, known as pulmonary arterial hypertension (PAH), is a rare disorder. In spite of recent advances in treatment, the death rate remains unacceptably high. Lung blood vessel function can be harmed by progressive injuries, such as inflammation, leading to worsening of the disease. A drug called spironolactone has been known to improve blood vessel function and reduce inflammation. Some people with PAH take spironolactone to help treat fluid retention. However, its effect on inflammation and blood vessel function in patients with PAH is not known. Researchers want to see if spironolactone can help these conditions in people with PAH. Objectives: \- To test the effectiveness of spironolactone in treating pulmonary arterial hypertension. Eligibility: \- Individuals at least 18 years of age with pulmonary arterial hypertension. Design: * This study will last for 24 weeks. Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. * Participants will take either spironolactone or a placebo. They will take their study drug or placebo for 7 weeks. Treatment will be monitored with regular blood tests. * In Week 8, participants who have had no reaction to the treatment will receive a higher dose of the drug or placebo. * In Week 12, participants will have a study visit with heart and lung function tests. They will also have a 6-minute walk test, and provide blood and urine samples. * After additional study visits for blood samples, participants will have a final visit in Week 24. The tests from Week 12 will be repeated at this visit.
Description
INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare disorder associated with poor survival. Endothelial dysfunction resulting from 1) genetic susceptibility, and 2) a triggering stimulus that initiates pulmonary vascular injury, the two-hit hypothesis, appears to play a central role both in the pathogenesis and progression of PAH. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic PAH (IPAH) and patients with disease-associated PAH. Therapy targeting pulmonary vascular in…
Eligibility
- Age range
- 18–100 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: 1. WHO Group 1 PH patients on either no medical therapy or stable medical therapy for at least the past 4 weeks (defined as no new PAH-specific therapy, no change in the dose of current PAH-specific therapy and no change in NYHA/WHO functional classification within the past 4 weeks) are eligible. The following parameters on RHC are required to meet the hemodynamic definition of PAH: <!-- --> 1. mean pulmonary artery pressure of \> 25 mmHg at rest, 2. pulmonary capillary wedge pressure of less than or equal to 15 mmHg (or a left ventricular end-diastolic pressur…
Interventions
- DrugSpironolactone
Initial dose, 25 mg (pink capsule) orally, daily. If well tolerated at 7-9 wks then increased to 50 mg (brown capsule) daily.
- DrugPlacebo
Initial dose, pink sugar capsule, daily. If well tolerated at 7-9 wks then changed to brown sugar capsule, daily.
Location
- National Institutes of Health Clinical CenterBethesda, Maryland