Ignite Creation Date:
2024-05-06 @ 1:03 AM
Last Modification Date:
2024-10-26 @ 10:58 AM
Study NCT ID:
NCT01712620
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2012-10-20
Brief Title:
Spironolactone for Pulmonary Arterial Hypertension
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot Study of the Effect of Spironolactone Therapy on Exercise Capacity and Endothelial Dysfunction in Pulmonary Arterial Hypertension
Status:
RECRUITING
Status Verified Date:
2024-08-28
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
- 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
Detailed 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 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 NYHAWHO 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
OBJECTIVES
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
METHODS
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
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 NYHAWHO 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
OBJECTIVES
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
METHODS
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 12-CC-0211 | None | None | None |