Effects of DHEA in Pulmonary Hypertension

Study Overview
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Brief Summary
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The goal of this crossover trial is to determine whether the study drug dehydroepiandrosterone (DHEA) improves right ventricular longitudinal strain measured by cardiac magnetic resonance imaging at 18 weeks compared to placebo and to assess side effects and safety in pulmonary arterial hypertension.

Official Title
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Effects of DHEA in Pulmonary Hypertension

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: DHEA tablet
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of PAH that is 1) idiopathic, 2) heritable or 3) associated with connective tissue disease, congenital systemic-to-pulmonary shunt, porto-pulmonary hypertension, drug or toxin use. Documentation of the following at any time prior to study entry: mPAP ≥ 25 mmHg at rest, pulmonary capillary wedge pressure or left ventricular end-diastolic pressure ≤ 15 mmHg, and PVR > 3 Wood units Pulmonary function testing documenting forced expiratory volume in one second/forced vital capacity ratio ≥ 70% predicted and total lung capacity ≥ 70% predicted If TLC is mildly reduced (60%<TLC%<70%), computerized tomography (HRCT or non-HRCT) documenting no significant interstitial lung disease may be used to fulfill this requirement. Chest tomography documenting no more than moderate parenchymal lung disease with clinician designated WHO I PAH and meeting both TLC and FEV1/FVC criteria. Normal or low probability V/Q scan If no V/Q scan is available, a CT angiogram documenting the absence of thromboembolic disease may be used, provided the subject meets diagnostic PAH criteria Exclusion Criteria: Age < 18 years old PAH associated with human immunodeficiency virus infection New background PAH therapy within 12 weeks Significant dose change in background PAH therapy within 12 weeks. Untreated severe obstructive sleep apnea diagnosed by polysomnography Evidence of left-sided valvular disease or systolic dysfunction on echocardiogram (≥ moderate mitral or aortic disease or LV ejection fraction ≤ 50%) Glomerular filtration rate <40 mls/min/1.73m2 Child-Pugh Class C cirrhosis Untreated hypo- or hyper-thyroidism Pregnant or breastfeeding Active or planned use of hormone supplements, oral contraceptive pills, hormonal therapies History of breast, ovarian, uterine, testicular or prostate cancer Current use of another investigational PAH therapy Contraindication to MRI (e.g., metal device or fragment) History of significant non-adherence or circumstance which would threaten ability to comply with cross-over design and study visit schedule

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DHEA<br>DHEA tablet (50 mg) taken by mouth once a day for 18 weeks | Drug: DHEA tablet<br>* DHEA tablet (50 mg) taken by mouth once a day for 18 weeks.<br>* Other names: Dehydroepiandrosterone;|
| Placebo Comparator: Placebo<br>1 placebo tablet taken by mouth once a day for 18 weeks | Other: Placebo<br>* 1 placebo tablet taken by mouth once a day for 18 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Right ventricular (RV) longitudinal strain | Change in global RV longitudinal strain measured by cardiac magnetic resonance imaging (MRI) between DHEA and placebo | 18 weeks, 40 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RV ejection fraction | Change in RV ejection fraction measured by cardiac MRI between DHEA and placebo | 18 weeks, 40 weeks | 
| NT-proBNP | Change in serum level of NT-proBNP between DHEA and placebo | 2 weeks, 18 weeks, 24 weeks, 40 weeks | 
| Sex hormone levels | Change in sex hormone levels between DHEA and placebo | 2 weeks, 18 weeks, 24 weeks, 40 weeks | 
| Six minute walk distance (6MWD) | Change in 6MWD between DHEA and placebo | 2 weeks, 18 weeks, 24 weeks, 40 weeks | 
| World Health Organization (WHO) Functional Class | Change in WHO Functional Class (I - IV with IV indicating worse symptoms) between DHEA and placebo | 2 weeks, 18 weeks, 24 weeks, 40 weeks | 
| Short Form-36 | Change in Short Form-36 summary scores for physical and mental components (range 0 - 100, higher scores indicating better quality of life) between DHEA and placebo | 2 weeks, 18 weeks, 24 weeks, 40 weeks | 
| emPHasis-10 | Change in emPHasis-10 score (range 0 - 50, higher scores indicating worse quality of life) between DHEA and placebo | 2 weeks, 18 weeks, 24 weeks, 40 weeks | 
| Treatment-related side effects and adverse events | Difference in treatment-related side effects and adverse events (as assessed by CTCAE v4.0) between DHEA and placebo | 2 weeks, 18 weeks, 24 weeks, 40 weeks, 42 weeks |