Effects of Spironolactone on Collagen Metabolism in Patients With Pulmonary Arterial Hypertension
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| ClinicalTrials.gov Identifier: NCT01468571 |
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Recruitment Status : Unknown
Verified May 2015 by Zeenat Safdar, Baylor College of Medicine.
Recruitment status was: Recruiting
First Posted : November 9, 2011
Last Update Posted : May 8, 2015
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Sponsor:
Baylor College of Medicine
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Zeenat Safdar, Baylor College of Medicine
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Pulmonary Hypertension | Drug: Spironolactone Drug: Placebo | Phase 4 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 50 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Effects of Spironolactone on Collagen Metabolism in Pulmonary Arterial Hypertension |
| Study Start Date : | July 2011 |
| Estimated Primary Completion Date : | July 2015 |
| Estimated Study Completion Date : | December 2015 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Pulmonary arterial hypertension
Drug Information available for:
Spironolactone
| Arm | Intervention/treatment |
|---|---|
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Experimental: Spironolactone
Drug: Spironolactone Drug: Placebo
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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.
Other Name: Aldactone |
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Experimental: Placebo
Drug: Placebo Drug: Spironolactone
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Drug: 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. Other Name: sugar pill |
Primary Outcome Measures :
- Change in biomarker levels in the spironolactone treated as compared to placebo treated group. [ Time Frame: 16 week ]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.
Secondary Outcome Measures :
- Number of adverse events in patients treated with spironolactone as compared to placebo. [ Time Frame: 16 week ]Safety and tolerability of spironolactone as compared to placebo in PAH.
- Change in six-minute walk distance from baseline to week 8 and week 16. [ Time Frame: 16 week ]
- Composite end-point [ Time Frame: 16 week ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01468571
Contacts
| Contact: Zeenat Safdar, MD | 713-798-2400 | safdar@bcm.edu | |
| Contact: Gwendolyn Goodloe | 713-798-2400 | gmb@bcm.edu |
Locations
| United States, Texas | |
| Baylor College of Medicine | Recruiting |
| Houston, Texas, United States, 77030 | |
Sponsors and Collaborators
Baylor College of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
| Principal Investigator: | Zeenat Safdar, MD | Baylor College of Medicine |
| Responsible Party: | Zeenat Safdar, Associate Professor of Medicine, Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT01468571 History of Changes |
| Other Study ID Numbers: |
H24178 K23HL093214 ( U.S. NIH Grant/Contract ) |
| First Posted: | November 9, 2011 Key Record Dates |
| Last Update Posted: | May 8, 2015 |
| Last Verified: | May 2015 |
Keywords provided by Zeenat Safdar, Baylor College of Medicine:
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Potassium Sparing Diuretics Right-sided heart failure Edema |
Additional relevant MeSH terms:
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Hypertension Hypertension, Pulmonary Familial Primary Pulmonary Hypertension Vascular Diseases Cardiovascular Diseases Lung Diseases Respiratory Tract Diseases Spironolactone |
Mineralocorticoid Receptor Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Diuretics, Potassium Sparing Diuretics Natriuretic Agents |