Spironolactone for Pulmonary Arterial Hypertension
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|ClinicalTrials.gov Identifier: NCT01712620|
Recruitment Status : Recruiting
First Posted : October 23, 2012
Last Update Posted : December 7, 2017
- 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 withPAH is not known. Researchers want to see if spironolactone can help these conditions in people with PAH.
- To test the effectiveness of spironolactone in treating pulmonary arterial hypertension.
- Individuals at least 18 years of age with pulmonary arterial hypertension.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Arterial Hypertension||Drug: Spironolactone Drug: Placebo||Phase 1 Phase 2|
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 inflammation to interrupt cycles of injury and repair and thereby delay or prevent RV failure and death has not been tested. Spironolactone, a mineralocorticoid receptor (MR) and androgen receptor (AR) antagonist, has been shown to improve endothelial function and reduce inflammation. Current management of patients with severe PAH and NYHA/WHO class IV symptoms includes use of MR antagonists for their diuretic and natriuretic effects once clinical right heart failure has developed. We hypothesize that initiating therapy with spironolactone at an earlier stage of disease in subjects with PAH could provide additional benefits through anti-inflammatory effects and improvements in pulmonary artery endothelial function.
Patients with IPAH and disease-associated PAH will be recruited to the NIH and enrolled in a randomized, double blinded, placebo-controlled study of early treatment with spironolactone to investigate its effects on exercise capacity, clinical worsening, and vascular inflammation in vivo.
The total number of PAH subjects enrolled will be up to 70. Subjects will undergo 1) standard clinical examinations including 6-minute walk distance and echocardiography; 2) cardiopulmonary exercise testing; 3) plasma profiling of inflammatory and neurohormonal markers; 4) gene expression profiling of peripheral blood mononuclear cells (PBMCs); and 5) high-resolution MRI-based determination of pulmonary vascular and RV structure and function. Safety and tolerability of spironolactone in PAH will be assessed with periodic monitoring for hyperkalemia and renal insufficiency as well as the incidence of drug discontinuation for untoward effects.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||A Pilot Study of the Effect of Spironolactone Therapy on Exercise Capacity and Endothelial Dysfunction in Pulmonary Arterial Hypertension|
|Study Start Date :||September 25, 2012|
|Estimated Primary Completion Date :||August 31, 2020|
|Estimated Study Completion Date :||August 31, 2021|
|Experimental: Group A||
Initial dose, 25 mg (pink capsule) orally, daily. If well tolerated at 7-9 wks then increased to 50 mg (brown capsule) daily.
|Placebo Comparator: Group B||
Initial dose, pink sugar capsule, daily. If well tolerated at 7-9 wks then changed to brown sugar capsule, daily.
- Change in placebo corrected 6-minute walk distance [ Time Frame: 6 months ]
- Clinical worsening [ Time Frame: 6 months ]
- Change in placebo corrected VO2 max [ Time Frame: 6 months ]
- Change in right ventricular function [ Time Frame: 6 months ]
- Biomarkers of vascular inflammation [ Time Frame: 6 months ]
- Rate of study drug discontinuation due to hyperkalemia, renal insufficiency, or other side effects such as breast pain and gynecomastia [ Time Frame: 6 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01712620
|Contact: Grace M Graninger, R.N.||(301) firstname.lastname@example.org|
|Contact: Michael A Solomon, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Michael A Solomon, M.D.||National Institutes of Health Clinical Center (CC)|