Phase 2
Completed N=26
Effects of DHEA in Pulmonary Hypertension
Source: ClinicalTrials.gov NCT03648385 ↗Enrolled (actual)
26
Serious AEs
14.4%
Results posted
Nov 2025
Primary outcomePrimary: Change in Right Ventricular (RV) Longitudinal Strain, % Cardiac Magnetic Resonance Imaging (MRI) — -16.8; -16.9; -17.7; -18.3 % Change in RV Longitudinal Strain — p=0.83
Summary
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 AND 40 weeks compared to placebo and to assess side effects and safety in pulmonary arterial hypertension.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Right Ventricular (RV) Longitudinal Strain, % Cardiac Magnetic Resonance Imaging (MRI) |
-16.8; -16.9; -17.7; -18.3; -17.2; -16.7 | 0.83 |
| PRIMARY Change in Right Ventricular (RV) †RV Radial Strain, %, |
22.2; 19.1; 21.1; 20.7; 19.3; 23.1 | 0.08 |
| PRIMARY †RV Circumferential Strain, % |
-14.3; -12.3; -13.7; -13.3; -12.8; -14.4 | 0.047 sig |
| PRIMARY RV End Diastolic Volume (RVEDV), mL |
156.7; 173.8; 160.4; 159.8; 161.4; 161.3 | 0.044 sig |
| PRIMARY Change in RV Ejection Fraction Measured by Cardiac MRI |
52.1; 49.4; 52.6; 50.3; 50.7; 49.2 | 0.91 |
| PRIMARY RVESV, mL |
73.6; 86.6; 74.2; 78.1; 78.2; 81.1 | 0.14 |
| PRIMARY RV Stroke Volume, mL |
80.1; 83.9; 81.6; 80.3; 80.9; 77.7 | 0.36 |
| PRIMARY RV Mass, g |
58.8; 55.7; 58.2; 52.2; 55.9; 54.1 | 0.55 |
| SECONDARY Change in Six Minute Walk Distance (6MWD) Between DHEA and Placebo |
433.58; 355.2; 428.3; 356.2; 402.1; 364.6 | 0.79 |
| SECONDARY Change in World Health Organization (WHO) Functional Class |
2.2; 2.3; 2.2; 2.4; 2.1; 2.3 | 0.33 |
| SECONDARY Change in Short Form-36 Summary Scores for Physical and Mental Components |
39.4; 42.8; 39.7; 38.9; 37.0; 41.7 | 0.13 |
| SECONDARY Change in emPHasis-10 |
25.4; 21.7; 25.5; 22.7; 27.3; 18.1 | 0.70 |
| SECONDARY Change in NT-proBNP Between DHEA and Placebo |
106.8; 205.9; 156.4; 139.3; 170.3; 146.9 | 0.005 sig |
| SECONDARY Change in DHEA-S (ug/dL) |
77.8; 48.2; 287.8; 49.3; 75.9; 169.9 | <0.0001 sig |
| SECONDARY Change in Estradiol, pg/mL |
46.3; 26.3; 60.7; 24.7; 34.5; 25.3 | 0.36 |
| SECONDARY Change in Testosterone, ng/dL |
23.8; 10.2; 65.6; 10.4; 27; 35.3 | 0.002 sig |
| SECONDARY Change in Progesterone, ng/mL |
0.6; 0.6; 0.6; 0.4; 0.8; 0.4 | 0.42 |
| SECONDARY Change in Follicle Stimulating Hormone (FSH), mIU/mL |
11.3; 21.5; 9.7; 23.5; 9.4; 25.5 | 0.08 |
| SECONDARY Change in Sex Hormone Binding Globulin (SHBG), Nmol/L |
57.8; 61; 50.2; 62.2; 59.3; 48 | 0.07 |
| SECONDARY Change in Luteinizing Hormone, mIU/mL |
12.5; 14.3; 10.3; 14.5; 8.6; 17.5 | 0.27 |
| SECONDARY Change in Prolactin, μIU/mL |
329.5; 287.8; 327.4; 293.8; 305.2; 271.4 | 0.81 |
| SECONDARY Change in C-peptide, ng/mL |
3.3; 3.6; 3.1; 3.3; 3; 3.4 | 0.93 |
| SECONDARY Change in Insulin, μU/mL |
11.4; 13.2; 10.7; 12.1; 10.8; 13.5 | 0.85 |
| SECONDARY Cortisol, μg/dL^2 |
11.7; 9.1; 9.2; 12.6; 12.9; 11.7 | 0.004 sig |
| SECONDARY Left Ventricular Ejection Fraction, % |
66.2; 71.8; 69.1; 71.4; 68.4; 73.4 | 0.33 |
| SECONDARY Left Ventricular End-diastolic Volume (LVEDV) (mL) |
104.9; 109.9; 107.7; 102.7; 105.3; 101 | 0.19 |
| SECONDARY Left Ventricular End-systolic Volume (LVESV) (mL) |
31; 31.4; 32.7; 30.5; 32.5; 26.1 | 0.62 |
| SECONDARY Left Ventricular Stroke Volume (mL) |
72.8; 78.4; 74.0; 75.5; 71.5; 72.2 | 0.33 |
| SECONDARY Left Ventricular End Diastolic Mass, g |
117.8; 119.3; 122.2; 119.5; 116.6; 114 | 0.55 |
| SECONDARY Treatment-related Side Effects and Adverse Events |
6; 0; 0; 2; 2; 0 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT03648385). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.