Pulmonary Arterial Hypertension
Conditions
Brief 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.
Detailed description
Pulmonary hypertension (PH) is a heterogenous clinical disease characterized foremost by an abnormal increase in pulmonary artery pressure. Pulmonary vasculopathy, characterized by pathologic remodeling and vasoconstriction of the pulmonary arterioles, results in progressive dyspnea, exercise intolerance, right ventricular (RV) failure, and death. Female sex is the strongest clinical risk factor for PAH, with a 4:1 female-to-male ratio reported from the largest registry. Despite the increased risk of PAH in women, women with PAH have better survival than men. RV function is an important cause of morbidity and mortality in PAH as well as highly prevalent heart and lung diseases, but determinants of the RV response are entirely unknown. We and others have shown that female sex is associated with better RV systolic function in both health and disease, including PAH and left heart failure. Targeted PAH therapy leads to greater improvements in RVEF (demonstrated after just several months of treatment) in women as compared to men and partially explains better outcomes in women. Demonstration that DHEA has direct RV and sex-based effects will support the hypothesis that sex hormones play an important role in disease pathogenesis and provide insight into sex hormone manipulation as a treatment strategy in PAH. The goal of this crossover trial is to correlate sex and sex hormones (particularly DHEA) to pulmonary vascular and RV phenotype differences in men and women with PAH. The study seeks to leverage a safe and available hormone treatment to gain further insight into 1) RV effects (a novel and critical end point in PH and PAH), 2) effects on two key PAH pathways in vivo and in vitro as a means for understanding sex-based differences in PAH, and 3) efficiency planning for a future Phase II parallel trial of DHEA as a novel treatment strategy in PAH.
Interventions
DRUGDHEA tablet
DHEA tablet (50 mg) taken by mouth once a day for 18 weeks. All participants in this crossover trial will receive DHEA during Treatment Period 1 or Treatment Period 2. There is a 4 week washout between Treatment Period 1 and Treatment Period 2
OTHERPlacebo
1 placebo tablet taken by mouth once a day for 18 weeks. All participants in this crossover trial will receive placebo during this crossover study during Treatment Period 1 or Treatment Period 2. There is a 4 week washout between Treatment Period 1 and Treatment Period 2
Sponsors
Rhode Island Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Right Ventricular (RV) Longitudinal Strain, % Cardiac Magnetic Resonance Imaging (MRI) | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Longitudinal strain is determined using standard cine imaging and Tissue Tracking (Strain) software (Tissue Tracking plugin, Circle Cardiovascular Imaging). Study MRIs were performed at a core MRI facility on a single Siemens 1.5T Aera with full Advanced Cardiac Package and XQ Gradients (45 mT/m @ 200 T/m/s) used for research grade imaging. 2D RV longitudinal strain: Measured from RV free wall of 4-chamber view cine CMR image. RV wall is divided into 6 equal segments. Strain can be either positive, which indicates lengthening, or negative, which indicates shortening. Normal circumferential and longitudinal strain are negative numbers, those for radial strain are positive. |
| Change in Right Ventricular (RV) †RV Radial Strain, %, | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | †Short axis, RV radial strain, % by Cardiac Magnetic Resonance Imaging (MRI). Study MRIs were performed at a core MRI facility on a single Siemens 1.5T Aera with full Advanced Cardiac Package and XQ Gradients (45 mT/m @ 200 T/m/s) used for research grade imaging. Measurements were made using CVI42, Circle Cardiovascular Imaging. 2D RV longitudinal strain: Measured from RV free wall of 4-chamber view cine CMR image. RV wall is divided into 6 equal segments. Strain can be either positive, which indicates lengthening, or negative, which indicates shortening. Normal circumferential and longitudinal strain are negative numbers, those for radial strain are positive. |
| †RV Circumferential Strain, % | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Circumferential strain is determined using standard cine imaging and Tissue Tracking (Strain) software (Tissue Tracking plugin, Circle Cardiovascular Imaging). Cardiac Study MRIs were performed at a core MRI facility on a single Siemens 1.5T Aera with full Advanced Cardiac Package and XQ Gradients (45 mT/m @ 200 T/m/s) used for research grade imaging. Measurements were made using CVI42, Circle Cardiovascular Imaging. 2D RV circumferential strain: Measured from RV free wall of 4-chamber view cine CMR image. RV wall is divided into 6 equal segments. Strain can be either positive, which indicates lengthening, or negative, which indicates shortening. Normal circumferential and longitudinal strain are negative numbers, those for radial strain are positive. |
| RV End Diastolic Volume (RVEDV), mL | 18 Weeks, 40 Weeks | % Change in RV End Diastolic Volume (RVEDV), mL by Cardiac Magnetic Resonance Imaging (MRI), strain from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging was obtained from the base of the heart through the apex. The endocardial and epicardial borders of both ventricles are be traced manually on short axis cine images at end-diastole and end-systole with exclusion of the papillary muscles and trabeculae. EDV and ESV are calculated using Simpson's rule by summation of areas on each slice multiplied by the sum of slice thickness and image gap. |
| Change in RV Ejection Fraction Measured by Cardiac MRI | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in RV ejection fraction measured by Cardiac Magnetic Resonance Imaging (MRI), % Change in strain from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging from the base of the heart through the apex. Ventricular EFs are calculated by dividing respective stroke volumes (EDV-ESV) by EDVs. |
| RVESV, mL | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in right ventricular end-systolic volume from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging was obtained from the base of the heart through the apex. The endocardial and epicardial borders of both ventricles are be traced manually on short axis cine images at end-diastole and end-systole with exclusion of the papillary muscles and trabeculae. EDV and ESV are calculated using Simpson's rule by summation of areas on each slice multiplied by the sum of slice thickness and image gap. |
| RV Stroke Volume, mL | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in Right ventricular stroke volume by cardiac MRI from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Stroke volume is calculated through breath-hold through-plane phase contrast imaging with a velocity encoding gradient (VENC) of \<120 cm/s (larger if aliasing present) in the main PA \ 2-3 cm above the pulmonary valve plane, with imaging plane oriented orthogonal to the main PA. Free-breathing phase contrast imaging in the same plane and VENC with averaging over 4 respiratory cycles. |
| RV Mass, g | 18 weeks, 40 weeks | Right ventricular mass, Change in RV mass from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging from the base of the heart through the apex. RV mass is determined at the end-diastole phase as the difference between end-diastolic epicardial and endocardial volumes X heart specific gravity (1.05 g/cm3). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Progesterone, ng/mL | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in Progesterone, ng/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups. |
| Change in Follicle Stimulating Hormone (FSH), mIU/mL | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in FSH, mIU/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups. |
| Change in Sex Hormone Binding Globulin (SHBG), Nmol/L | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in SHBG, nmol/L from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups. |
| Change in Luteinizing Hormone, mIU/mL | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in Luteinizing hormone, mIU/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups. |
| Change in Prolactin, μIU/mL | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in Prolactin, μIU/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups. |
| Change in C-peptide, ng/mL | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in C-peptide, ng/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups. |
| Change in Insulin, μU/mL | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in Insulin, μU/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups. |
| Change in NT-proBNP Between DHEA and Placebo | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in serum level of NT-proBNP between DHEA and placebo. |
| Left Ventricular Ejection Fraction, % | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in left ventricular ejection fraction (%) measured by Cardiac Magnetic Resonance Imaging (MRI). Change in LVEG from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging from the base of the heart through the apex was used.. Ventricular EFs are calculated by dividing respective stroke volumes (EDV-ESV) by EDVs. Normal Values: 56-78% for both males and females. |
| Left Ventricular End-diastolic Volume (LVEDV) (mL) | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in left ventricular LVEDV measured by Cardiac Magnetic Resonance Imaging (MRI). Change in LVEDV from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging was obtained from the base of the heart through the apex. The endocardial and epicardial borders of both ventricles are be traced manually on short axis cine images at end-diastole and end-systole with exclusion of the papillary muscles and trabeculae. EDV and ESV are calculated using Simpson's rule by summation of areas on each slice multiplied by the sum of slice thickness and image gap. Normal values (Male):77-195 ml. Normal values (female):58-154 ml. |
| Left Ventricular End-systolic Volume (LVESV) (mL) | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in LVESV measured by Cardiac Magnetic Resonance Imaging (MRI). Change in LVEDV from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging was obtained from the base of the heart through the apex. The endocardial and epicardial borders of both ventricles are be traced manually on short axis cine images at end-diastole and end-systole with exclusion of the papillary muscles and trabeculae. EDV and ESV are calculated using Simpson's rule by summation of areas on each slice multiplied by the sum of slice thickness and image gap. Normal Values (Female):13-51 ml. Normal values (Male):19-72 ml |
| Left Ventricular Stroke Volume (mL) | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in Left ventricular stroke volume measured by Cardiac Magnetic Resonance Imaging (MRI). Change in Left ventricular stroke volume from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Stroke volume is calculated through breath-hold through-plane phase contrast imaging with a velocity encoding gradient (VENC) of \<120 cm/s (larger if aliasing present) in the main PA \ 2-3 cm above the pulmonary valve plane, with imaging plane oriented orthogonal to the main PA. Free-breathing phase contrast imaging in the same plane and VENC with averaging over 4 respiratory cycles. |
| Left Ventricular End Diastolic Mass, g | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in Left ventricular end diastolic mass, g measured by Cardiac Magnetic Resonance Imaging (MRI). Change in Left ventricular end diastolic mass, g from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging from the base of the heart through the apex. LV mass is determined at the end-diastole phase as the difference between end-diastolic epicardial and endocardial volumes X heart specific gravity (1.05 g/cm3). |
| Treatment-related Side Effects and Adverse Events | 18 weeks, 40 weeks | Treatment-related side effects and adverse events (as assessed by CTCAE v4.0). All participants in this trial received both DHEA and Placebo during the trial, therefore, side-effects and adverse events are listed according to the treatment or washout period in which they occurred. |
| Cortisol, μg/dL^2 | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in Cortisol, μg/dL\^2 (micrograms per deciliter squared) from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups. |
| Change in DHEA-S (ug/dL) | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in DHEA-S from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups. |
| Change in Estradiol, pg/mL | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in Estradiol, pg/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups. |
| Change in Six Minute Walk Distance (6MWD) Between DHEA and Placebo | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in 6MWD from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups. |
| Change in World Health Organization (WHO) Functional Class | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in WHO Functional Class (I - IV with IV indicating worse symptoms) between DHEA and placebo. |
| Change in Short Form-36 Summary Scores for Physical and Mental Components | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in Short Form-36 summary scores for physical and mental components (range 0 - 100, higher scores indicating better quality of life). |
| Change in emPHasis-10 | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in emPHasis-10 score (range 0 - 50, higher scores indicating worse quality of life) between DHEA and placebo. |
| Change in Testosterone, ng/dL | Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2) | Change in Testosterone, ng/dL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DHEA to placebo DHEA tablet (50 mg) taken by mouth once a day for 18 weeks
DHEA tablet: DHEA tablet (50 mg) taken by mouth once a day for 18 weeks.
then
Placebo: 1 placebo tablet taken by mouth once a day for 18 weeks | 14 |
| Placebo to DHEA 1 placebo tablet taken by mouth once a day for 18 weeks
Placebo: 1 placebo tablet taken by mouth once a day for 18 weeks
then
DHEA tablet: DHEA tablet (50 mg) taken by mouth once a day for 18 weeks. | 12 |
| Total | 26 |
Baseline characteristics
| Characteristic | Placebo to DHEA | DHEA to placebo | Total |
|---|---|---|---|
| 6MWD | 420 meters | 437 meters | 430 meters |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 12 Participants | 20 Participants |
| Age, Continuous | 54 years | 44 years | 48 years |
| BMI | 34 kg/m2 | 32 kg/m2 | 32 kg/m2 |
| Cardiac Index L/min/m^2 | 2.7 L/min/m^2 | 2.9 L/min/m^2 | 2.8 L/min/m^2 |
| EmPHasis10 | 19 units on a scale | 25 units on a scale | 25 units on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 11 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Functional Class II | 8 Participants | 11 Participants | 19 Participants |
| Functional Class III | 4 Participants | 3 Participants | 7 Participants |
| Mean PAP | 50 mmHg | 43 mmHg | 45 mmHg |
| N-terminal proBNP, pg/mL | 193.2 pg/mL | 79.9 pg/mL | 127.6 pg/mL |
| PAH Diagnosis Congenital Heart Disease | 0 Participants | 1 Participants | 1 Participants |
| PAH Diagnosis Connective Tissue Disease | 4 Participants | 5 Participants | 9 Participants |
| PAH Diagnosis Drug and Toxin | 1 Participants | 0 Participants | 1 Participants |
| PAH Diagnosis Heritable | 2 Participants | 3 Participants | 5 Participants |
| PAH Diagnosis Idiopathic | 5 Participants | 5 Participants | 10 Participants |
| PAOP, mm Hg | 13 mmHg | 11 mmHg | 11 mmHg |
| PVR, Wood units | 8 woods units | 5 woods units | 6 woods units |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 10 Participants | 19 Participants |
| Region of Enrollment United States | 12 participants | 14 participants | 26 participants |
| Right atrial pressure, mmHg | 10 mmHg | 7 mmHg | 10 mmHg |
| RV circumferential strain, % | -12.2 % | -14.8 % | -13.3 % |
| RVEDV, mL | 181 mL | 147 mL | 163 mL |
| RVEF, % | 51 % | 55 % | 53 % |
| RVESV, mL | 92 mL | 62 mL | 71 mL |
| RV Longitudinal Strain, % | -18.8 % | -18.4 % | -18.8 % |
| RV mass, g | 55 grams | 55 grams | 55 grams |
| RV peak global radial strain, % | 18.9 % | 22.4 % | 20 % |
| †RV radial strain, % | 18.9 % | 22.4 % | 20 % |
| RV stroke volume, mL | 83 mL | 82 mL | 82 mL |
| Sex: Female, Male Total Female | 2 Participants | 10 Participants | 12 Participants |
| Sex: Female, Male Total Male | 10 Participants | 4 Participants | 14 Participants |
| Short-Form 36 MCS | 54 units on a scale | 48 units on a scale | 49 units on a scale |
| Short-Form 36 PCS | 45 units on a scale | 38 units on a scale | 40 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 26 | 0 / 26 | 0 / 26 |
| other Total, other adverse events | 16 / 26 | 16 / 26 | 2 / 26 | 6 / 26 |
| serious Total, serious adverse events | 2 / 26 | 10 / 26 | 1 / 26 | 2 / 26 |
Outcome results
Primary
Change in Right Ventricular (RV) Longitudinal Strain, % Cardiac Magnetic Resonance Imaging (MRI)
Longitudinal strain is determined using standard cine imaging and Tissue Tracking (Strain) software (Tissue Tracking plugin, Circle Cardiovascular Imaging). Study MRIs were performed at a core MRI facility on a single Siemens 1.5T Aera with full Advanced Cardiac Package and XQ Gradients (45 mT/m @ 200 T/m/s) used for research grade imaging. 2D RV longitudinal strain: Measured from RV free wall of 4-chamber view cine CMR image. RV wall is divided into 6 equal segments. Strain can be either positive, which indicates lengthening, or negative, which indicates shortening. Normal circumferential and longitudinal strain are negative numbers, those for radial strain are positive.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
Population: All patients receive both DHEA and placebo during this crossover study. One group received DHEA first, followed by a washout period, then placebo. The second group received placebo first, followed by a washout period, then DHEA.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in Right Ventricular (RV) Longitudinal Strain, % Cardiac Magnetic Resonance Imaging (MRI) | -16.8 % Change in RV Longitudinal Strain |
| Placebo to DHEA, Baseline | Change in Right Ventricular (RV) Longitudinal Strain, % Cardiac Magnetic Resonance Imaging (MRI) | -16.9 % Change in RV Longitudinal Strain |
| DHEA to placebo, 18 Weeks | Change in Right Ventricular (RV) Longitudinal Strain, % Cardiac Magnetic Resonance Imaging (MRI) | -17.7 % Change in RV Longitudinal Strain |
| Placebo to DHEA, 18 Weeks | Change in Right Ventricular (RV) Longitudinal Strain, % Cardiac Magnetic Resonance Imaging (MRI) | -18.3 % Change in RV Longitudinal Strain |
| DHEA to Placebo, 40 Weeks | Change in Right Ventricular (RV) Longitudinal Strain, % Cardiac Magnetic Resonance Imaging (MRI) | -17.2 % Change in RV Longitudinal Strain |
| Placebo to DHEA, 40 weeks | Change in Right Ventricular (RV) Longitudinal Strain, % Cardiac Magnetic Resonance Imaging (MRI) | -16.7 % Change in RV Longitudinal Strain |
Comparison: Treatment period 1: DHEA to Placebo group, measurement of % change at 18 Weeks Treatment period 1: Placebo to DHEA group, % change at 18 Weeksp-value: 0.83generalized estimating equations (GEE) w
Comparison: Treatment period 2: DHEA to Placebo group, % change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, % change between 18 and 40 Weeksp-value: 0.56generalized estimating equations (GEE) w
Primary
Change in Right Ventricular (RV) †RV Radial Strain, %,
†Short axis, RV radial strain, % by Cardiac Magnetic Resonance Imaging (MRI). Study MRIs were performed at a core MRI facility on a single Siemens 1.5T Aera with full Advanced Cardiac Package and XQ Gradients (45 mT/m @ 200 T/m/s) used for research grade imaging. Measurements were made using CVI42, Circle Cardiovascular Imaging. 2D RV longitudinal strain: Measured from RV free wall of 4-chamber view cine CMR image. RV wall is divided into 6 equal segments. Strain can be either positive, which indicates lengthening, or negative, which indicates shortening. Normal circumferential and longitudinal strain are negative numbers, those for radial strain are positive.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in Right Ventricular (RV) †RV Radial Strain, %, | 22.2 % Change in RV radial strain |
| Placebo to DHEA, Baseline | Change in Right Ventricular (RV) †RV Radial Strain, %, | 19.1 % Change in RV radial strain |
| DHEA to placebo, 18 Weeks | Change in Right Ventricular (RV) †RV Radial Strain, %, | 21.1 % Change in RV radial strain |
| Placebo to DHEA, 18 Weeks | Change in Right Ventricular (RV) †RV Radial Strain, %, | 20.7 % Change in RV radial strain |
| DHEA to Placebo, 40 Weeks | Change in Right Ventricular (RV) †RV Radial Strain, %, | 19.3 % Change in RV radial strain |
| Placebo to DHEA, 40 weeks | Change in Right Ventricular (RV) †RV Radial Strain, %, | 23.1 % Change in RV radial strain |
Comparison: Treatment period 1: DHEA to Placebo group, measurement of % change at 18 Weeks Treatment period 1: Placebo to DHEA group, % change at 18 Weeksp-value: 0.08generalized estimating equations (GEE) w
Comparison: Treatment period 2: DHEA to Placebo group, % change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, % change between 18 and 40 Weeksp-value: 0.03generalized estimating equations (GEE)
Primary
Change in RV Ejection Fraction Measured by Cardiac MRI
Change in RV ejection fraction measured by Cardiac Magnetic Resonance Imaging (MRI), % Change in strain from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging from the base of the heart through the apex. Ventricular EFs are calculated by dividing respective stroke volumes (EDV-ESV) by EDVs.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in RV Ejection Fraction Measured by Cardiac MRI | 52.1 % Change in RV ejection fraction |
| Placebo to DHEA, Baseline | Change in RV Ejection Fraction Measured by Cardiac MRI | 49.4 % Change in RV ejection fraction |
| DHEA to placebo, 18 Weeks | Change in RV Ejection Fraction Measured by Cardiac MRI | 52.6 % Change in RV ejection fraction |
| Placebo to DHEA, 18 Weeks | Change in RV Ejection Fraction Measured by Cardiac MRI | 50.3 % Change in RV ejection fraction |
| DHEA to Placebo, 40 Weeks | Change in RV Ejection Fraction Measured by Cardiac MRI | 50.7 % Change in RV ejection fraction |
| Placebo to DHEA, 40 weeks | Change in RV Ejection Fraction Measured by Cardiac MRI | 49.2 % Change in RV ejection fraction |
Comparison: Treatment period 1: DHEA to Placebo group, measurement of % change at 18 Weeks Treatment period 1: Placebo to DHEA group, % change at 18 Weeksp-value: 0.91generalized estimating equations (GEE)
Comparison: Treatment period 2: DHEA to Placebo group, % change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, % change between 18 and 40 Weeksp-value: 0.61generalized estimating equations (GEE) w
Primary
†RV Circumferential Strain, %
Circumferential strain is determined using standard cine imaging and Tissue Tracking (Strain) software (Tissue Tracking plugin, Circle Cardiovascular Imaging). Cardiac Study MRIs were performed at a core MRI facility on a single Siemens 1.5T Aera with full Advanced Cardiac Package and XQ Gradients (45 mT/m @ 200 T/m/s) used for research grade imaging. Measurements were made using CVI42, Circle Cardiovascular Imaging. 2D RV circumferential strain: Measured from RV free wall of 4-chamber view cine CMR image. RV wall is divided into 6 equal segments. Strain can be either positive, which indicates lengthening, or negative, which indicates shortening. Normal circumferential and longitudinal strain are negative numbers, those for radial strain are positive.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | †RV Circumferential Strain, % | -14.3 % Change in RV circumferential strain |
| Placebo to DHEA, Baseline | †RV Circumferential Strain, % | -12.3 % Change in RV circumferential strain |
| DHEA to placebo, 18 Weeks | †RV Circumferential Strain, % | -13.7 % Change in RV circumferential strain |
| Placebo to DHEA, 18 Weeks | †RV Circumferential Strain, % | -13.3 % Change in RV circumferential strain |
| DHEA to Placebo, 40 Weeks | †RV Circumferential Strain, % | -12.8 % Change in RV circumferential strain |
| Placebo to DHEA, 40 weeks | †RV Circumferential Strain, % | -14.4 % Change in RV circumferential strain |
Comparison: Treatment period 1: DHEA to Placebo group, measurement of % change at 18 Weeks Treatment period 1: Placebo to DHEA group, % change at 18 Weeksp-value: 0.047generalized estimating equations
Comparison: Treatment period 2: DHEA to Placebo group, % change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, % change between 18 and 40 Weeksp-value: 0.052generalized estimating equations (GEE)
Primary
RV End Diastolic Volume (RVEDV), mL
% Change in RV End Diastolic Volume (RVEDV), mL by Cardiac Magnetic Resonance Imaging (MRI), strain from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging was obtained from the base of the heart through the apex. The endocardial and epicardial borders of both ventricles are be traced manually on short axis cine images at end-diastole and end-systole with exclusion of the papillary muscles and trabeculae. EDV and ESV are calculated using Simpson's rule by summation of areas on each slice multiplied by the sum of slice thickness and image gap.
Time frame: 18 Weeks, 40 Weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | RV End Diastolic Volume (RVEDV), mL | 156.7 mL |
| Placebo to DHEA, Baseline | RV End Diastolic Volume (RVEDV), mL | 173.8 mL |
| DHEA to placebo, 18 Weeks | RV End Diastolic Volume (RVEDV), mL | 160.4 mL |
| Placebo to DHEA, 18 Weeks | RV End Diastolic Volume (RVEDV), mL | 159.8 mL |
| DHEA to Placebo, 40 Weeks | RV End Diastolic Volume (RVEDV), mL | 161.4 mL |
| Placebo to DHEA, 40 weeks | RV End Diastolic Volume (RVEDV), mL | 161.3 mL |
Comparison: Treatment period 1: DHEA to Placebo group, measurement of % change at 18 Weeks Treatment period 1: Placebo to DHEA group, % change at 18 Weeksp-value: 0.044generalized estimating equations (GEE) w
Comparison: Treatment period 2: DHEA to Placebo group, % change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, % change between 18 and 40 Weeksp-value: 0.96generalized estimating equations (GEE)
Primary
RVESV, mL
Change in right ventricular end-systolic volume from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging was obtained from the base of the heart through the apex. The endocardial and epicardial borders of both ventricles are be traced manually on short axis cine images at end-diastole and end-systole with exclusion of the papillary muscles and trabeculae. EDV and ESV are calculated using Simpson's rule by summation of areas on each slice multiplied by the sum of slice thickness and image gap.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | RVESV, mL | 73.6 mL |
| Placebo to DHEA, Baseline | RVESV, mL | 86.6 mL |
| DHEA to placebo, 18 Weeks | RVESV, mL | 74.2 mL |
| Placebo to DHEA, 18 Weeks | RVESV, mL | 78.1 mL |
| DHEA to Placebo, 40 Weeks | RVESV, mL | 78.2 mL |
| Placebo to DHEA, 40 weeks | RVESV, mL | 81.1 mL |
Comparison: Treatment period 1: DHEA to Placebo group, measurement of % change at 18 Weeks Treatment period 1: Placebo to DHEA group, % change at 18 Weeksp-value: 0.14generalized estimating equations
Comparison: Treatment period 2: DHEA to Placebo group, % change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, % change between 18 and 40 Weeksp-value: 0.84generalized estimating equations
Primary
RV Mass, g
Right ventricular mass, Change in RV mass from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging from the base of the heart through the apex. RV mass is determined at the end-diastole phase as the difference between end-diastolic epicardial and endocardial volumes X heart specific gravity (1.05 g/cm3).
Time frame: 18 weeks, 40 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | RV Mass, g | 58.8 g |
| Placebo to DHEA, Baseline | RV Mass, g | 55.7 g |
| DHEA to placebo, 18 Weeks | RV Mass, g | 58.2 g |
| Placebo to DHEA, 18 Weeks | RV Mass, g | 52.2 g |
| DHEA to Placebo, 40 Weeks | RV Mass, g | 55.9 g |
| Placebo to DHEA, 40 weeks | RV Mass, g | 54.1 g |
Comparison: Treatment period 1: DHEA to Placebo group, measurement of % change at 18 Weeks Treatment period 1: Placebo to DHEA group, % change at 18 Weeksp-value: 0.55generalized estimating equations
Comparison: Treatment period 2: DHEA to Placebo group, % change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, % change between 18 and 40 Weeksp-value: 0.44generalized estimating equations
Primary
RV Stroke Volume, mL
Change in Right ventricular stroke volume by cardiac MRI from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Stroke volume is calculated through breath-hold through-plane phase contrast imaging with a velocity encoding gradient (VENC) of \<120 cm/s (larger if aliasing present) in the main PA \ 2-3 cm above the pulmonary valve plane, with imaging plane oriented orthogonal to the main PA. Free-breathing phase contrast imaging in the same plane and VENC with averaging over 4 respiratory cycles.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | RV Stroke Volume, mL | 80.1 mL |
| Placebo to DHEA, Baseline | RV Stroke Volume, mL | 83.9 mL |
| DHEA to placebo, 18 Weeks | RV Stroke Volume, mL | 81.6 mL |
| Placebo to DHEA, 18 Weeks | RV Stroke Volume, mL | 80.3 mL |
| DHEA to Placebo, 40 Weeks | RV Stroke Volume, mL | 80.9 mL |
| Placebo to DHEA, 40 weeks | RV Stroke Volume, mL | 77.7 mL |
Comparison: Treatment period 1: DHEA to Placebo group, measurement of % change at 18 Weeks Treatment period 1: Placebo to DHEA group, % change at 18 Weeksp-value: 0.36generalized estimating equations
Comparison: Treatment period 2: DHEA to Placebo group, % change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, % change between 18 and 40 Weeksp-value: 0.71generalized estimating equations
Secondary
Change in C-peptide, ng/mL
Change in C-peptide, ng/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in C-peptide, ng/mL | 3.3 ng/mL |
| Placebo to DHEA, Baseline | Change in C-peptide, ng/mL | 3.6 ng/mL |
| DHEA to placebo, 18 Weeks | Change in C-peptide, ng/mL | 3.1 ng/mL |
| Placebo to DHEA, 18 Weeks | Change in C-peptide, ng/mL | 3.3 ng/mL |
| DHEA to Placebo, 40 Weeks | Change in C-peptide, ng/mL | 3 ng/mL |
| Placebo to DHEA, 40 weeks | Change in C-peptide, ng/mL | 3.4 ng/mL |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.93generalized estimating equations
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.83generalized estimating equations (GEE)
Secondary
Change in DHEA-S (ug/dL)
Change in DHEA-S from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in DHEA-S (ug/dL) | 77.8 ug/dL |
| Placebo to DHEA, Baseline | Change in DHEA-S (ug/dL) | 48.2 ug/dL |
| DHEA to placebo, 18 Weeks | Change in DHEA-S (ug/dL) | 287.8 ug/dL |
| Placebo to DHEA, 18 Weeks | Change in DHEA-S (ug/dL) | 49.3 ug/dL |
| DHEA to Placebo, 40 Weeks | Change in DHEA-S (ug/dL) | 75.9 ug/dL |
| Placebo to DHEA, 40 weeks | Change in DHEA-S (ug/dL) | 169.9 ug/dL |
Comparison: Treatment period 1: DHEA to Placebo group, measurement of % change at 18 Weeks Treatment period 1: Placebo to DHEA group, % change at 18 Weeksp-value: <0.0001generalized estimating equations (GEE)
Comparison: Treatment period 2: DHEA to Placebo group, % change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, % change between 18 and 40 Weeksp-value: 0.034generalized estimating equations (GEE)
Secondary
Change in emPHasis-10
Change in emPHasis-10 score (range 0 - 50, higher scores indicating worse quality of life) between DHEA and placebo.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in emPHasis-10 | 25.4 score on a scale |
| Placebo to DHEA, Baseline | Change in emPHasis-10 | 21.7 score on a scale |
| DHEA to placebo, 18 Weeks | Change in emPHasis-10 | 25.5 score on a scale |
| Placebo to DHEA, 18 Weeks | Change in emPHasis-10 | 22.7 score on a scale |
| DHEA to Placebo, 40 Weeks | Change in emPHasis-10 | 27.3 score on a scale |
| Placebo to DHEA, 40 weeks | Change in emPHasis-10 | 18.1 score on a scale |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.7generalized estimating equations (GEE)
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.037generalized estimating equations (GEE)
Secondary
Change in Estradiol, pg/mL
Change in Estradiol, pg/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in Estradiol, pg/mL | 46.3 pg/mL |
| Placebo to DHEA, Baseline | Change in Estradiol, pg/mL | 26.3 pg/mL |
| DHEA to placebo, 18 Weeks | Change in Estradiol, pg/mL | 60.7 pg/mL |
| Placebo to DHEA, 18 Weeks | Change in Estradiol, pg/mL | 24.7 pg/mL |
| DHEA to Placebo, 40 Weeks | Change in Estradiol, pg/mL | 34.5 pg/mL |
| Placebo to DHEA, 40 weeks | Change in Estradiol, pg/mL | 25.3 pg/mL |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, at 18 Weeksp-value: 0.36generalized estimating equations (GEE)
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.23generalized estimating equations (GEE)
Secondary
Change in Follicle Stimulating Hormone (FSH), mIU/mL
Change in FSH, mIU/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in Follicle Stimulating Hormone (FSH), mIU/mL | 11.3 mIU/mL |
| Placebo to DHEA, Baseline | Change in Follicle Stimulating Hormone (FSH), mIU/mL | 21.5 mIU/mL |
| DHEA to placebo, 18 Weeks | Change in Follicle Stimulating Hormone (FSH), mIU/mL | 9.7 mIU/mL |
| Placebo to DHEA, 18 Weeks | Change in Follicle Stimulating Hormone (FSH), mIU/mL | 23.5 mIU/mL |
| DHEA to Placebo, 40 Weeks | Change in Follicle Stimulating Hormone (FSH), mIU/mL | 9.4 mIU/mL |
| Placebo to DHEA, 40 weeks | Change in Follicle Stimulating Hormone (FSH), mIU/mL | 25.5 mIU/mL |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.08generalized estimating equations (GEE)
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.65generalized estimating equations (GEE)
Secondary
Change in Insulin, μU/mL
Change in Insulin, μU/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in Insulin, μU/mL | 11.4 μU/mL |
| Placebo to DHEA, Baseline | Change in Insulin, μU/mL | 13.2 μU/mL |
| DHEA to placebo, 18 Weeks | Change in Insulin, μU/mL | 10.7 μU/mL |
| Placebo to DHEA, 18 Weeks | Change in Insulin, μU/mL | 12.1 μU/mL |
| DHEA to Placebo, 40 Weeks | Change in Insulin, μU/mL | 10.8 μU/mL |
| Placebo to DHEA, 40 weeks | Change in Insulin, μU/mL | 13.5 μU/mL |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.85generalized estimating equations
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.74generalized estimating equations (GEE)
Secondary
Change in Luteinizing Hormone, mIU/mL
Change in Luteinizing hormone, mIU/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in Luteinizing Hormone, mIU/mL | 12.5 mIU/mL |
| Placebo to DHEA, Baseline | Change in Luteinizing Hormone, mIU/mL | 14.3 mIU/mL |
| DHEA to placebo, 18 Weeks | Change in Luteinizing Hormone, mIU/mL | 10.3 mIU/mL |
| Placebo to DHEA, 18 Weeks | Change in Luteinizing Hormone, mIU/mL | 14.5 mIU/mL |
| DHEA to Placebo, 40 Weeks | Change in Luteinizing Hormone, mIU/mL | 8.6 mIU/mL |
| Placebo to DHEA, 40 weeks | Change in Luteinizing Hormone, mIU/mL | 17.5 mIU/mL |
Comparison: Treatment period 1: DHEA to Placebo group, measurement of change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.27generalized estimating equations
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.26generalized estimating equations (GEE)
Secondary
Change in NT-proBNP Between DHEA and Placebo
Change in serum level of NT-proBNP between DHEA and placebo.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in NT-proBNP Between DHEA and Placebo | 106.8 pg/mL |
| Placebo to DHEA, Baseline | Change in NT-proBNP Between DHEA and Placebo | 205.9 pg/mL |
| DHEA to placebo, 18 Weeks | Change in NT-proBNP Between DHEA and Placebo | 156.4 pg/mL |
| Placebo to DHEA, 18 Weeks | Change in NT-proBNP Between DHEA and Placebo | 139.3 pg/mL |
| DHEA to Placebo, 40 Weeks | Change in NT-proBNP Between DHEA and Placebo | 170.3 pg/mL |
| Placebo to DHEA, 40 weeks | Change in NT-proBNP Between DHEA and Placebo | 146.9 pg/mL |
Comparison: Treatment period 1: DHEA to Placebo group, measurement of % change at 18 Weeks Treatment period 1: Placebo to DHEA group, % change at 18 Weeksp-value: 0.005generalized estimating equations (GEE)
Comparison: Treatment period 2: DHEA to Placebo group, % change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, % change between 18 and 40 Weeksp-value: 0.9generalized estimating equations (GEE)
Secondary
Change in Progesterone, ng/mL
Change in Progesterone, ng/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in Progesterone, ng/mL | 0.6 ng/mL |
| Placebo to DHEA, Baseline | Change in Progesterone, ng/mL | 0.6 ng/mL |
| DHEA to placebo, 18 Weeks | Change in Progesterone, ng/mL | 0.6 ng/mL |
| Placebo to DHEA, 18 Weeks | Change in Progesterone, ng/mL | 0.4 ng/mL |
| DHEA to Placebo, 40 Weeks | Change in Progesterone, ng/mL | 0.8 ng/mL |
| Placebo to DHEA, 40 weeks | Change in Progesterone, ng/mL | 0.4 ng/mL |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.42generalized estimating equations (GEE)
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.28generalized estimating equations (GEE)
Secondary
Change in Prolactin, μIU/mL
Change in Prolactin, μIU/mL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in Prolactin, μIU/mL | 329.5 μIU/mL |
| Placebo to DHEA, Baseline | Change in Prolactin, μIU/mL | 287.8 μIU/mL |
| DHEA to placebo, 18 Weeks | Change in Prolactin, μIU/mL | 327.4 μIU/mL |
| Placebo to DHEA, 18 Weeks | Change in Prolactin, μIU/mL | 293.8 μIU/mL |
| DHEA to Placebo, 40 Weeks | Change in Prolactin, μIU/mL | 305.2 μIU/mL |
| Placebo to DHEA, 40 weeks | Change in Prolactin, μIU/mL | 271.4 μIU/mL |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.81generalized estimating equations
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.94generalized estimating equations (GEE)
Secondary
Change in Sex Hormone Binding Globulin (SHBG), Nmol/L
Change in SHBG, nmol/L from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in Sex Hormone Binding Globulin (SHBG), Nmol/L | 57.8 nmol/L |
| Placebo to DHEA, Baseline | Change in Sex Hormone Binding Globulin (SHBG), Nmol/L | 61 nmol/L |
| DHEA to placebo, 18 Weeks | Change in Sex Hormone Binding Globulin (SHBG), Nmol/L | 50.2 nmol/L |
| Placebo to DHEA, 18 Weeks | Change in Sex Hormone Binding Globulin (SHBG), Nmol/L | 62.2 nmol/L |
| DHEA to Placebo, 40 Weeks | Change in Sex Hormone Binding Globulin (SHBG), Nmol/L | 59.3 nmol/L |
| Placebo to DHEA, 40 weeks | Change in Sex Hormone Binding Globulin (SHBG), Nmol/L | 48 nmol/L |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.07generalized estimating equations (GEE)
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: <0.01generalized estimating equations (GEE)
Secondary
Change in Short Form-36 Summary Scores for Physical and Mental Components
Change in Short Form-36 summary scores for physical and mental components (range 0 - 100, higher scores indicating better quality of life).
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DHEA to Placebo, Baseline | Change in Short Form-36 Summary Scores for Physical and Mental Components | SF-36, MCS | 45.1 score on a scale |
| DHEA to Placebo, Baseline | Change in Short Form-36 Summary Scores for Physical and Mental Components | SF-36, PCS | 39.4 score on a scale |
| Placebo to DHEA, Baseline | Change in Short Form-36 Summary Scores for Physical and Mental Components | SF-36, MCS | 49.1 score on a scale |
| Placebo to DHEA, Baseline | Change in Short Form-36 Summary Scores for Physical and Mental Components | SF-36, PCS | 42.8 score on a scale |
| DHEA to placebo, 18 Weeks | Change in Short Form-36 Summary Scores for Physical and Mental Components | SF-36, MCS | 43.6 score on a scale |
| DHEA to placebo, 18 Weeks | Change in Short Form-36 Summary Scores for Physical and Mental Components | SF-36, PCS | 39.7 score on a scale |
| Placebo to DHEA, 18 Weeks | Change in Short Form-36 Summary Scores for Physical and Mental Components | SF-36, MCS | 46.2 score on a scale |
| Placebo to DHEA, 18 Weeks | Change in Short Form-36 Summary Scores for Physical and Mental Components | SF-36, PCS | 38.9 score on a scale |
| DHEA to Placebo, 40 Weeks | Change in Short Form-36 Summary Scores for Physical and Mental Components | SF-36, PCS | 37.0 score on a scale |
| DHEA to Placebo, 40 Weeks | Change in Short Form-36 Summary Scores for Physical and Mental Components | SF-36, MCS | 45.2 score on a scale |
| Placebo to DHEA, 40 weeks | Change in Short Form-36 Summary Scores for Physical and Mental Components | SF-36, PCS | 41.7 score on a scale |
| Placebo to DHEA, 40 weeks | Change in Short Form-36 Summary Scores for Physical and Mental Components | SF-36, MCS | 47.9 score on a scale |
Comparison: SF-36 PCSp-value: 0.13generalized estimating equations (GEE)
Comparison: SF-36 PCSp-value: 0.044generalized estimating equations (GEE)
Comparison: SF-36 MCSp-value: 0.77generalized estimating equations (GEE)
Comparison: SF-MCSp-value: 0.98generalized estimating equations (GEE)
Secondary
Change in Six Minute Walk Distance (6MWD) Between DHEA and Placebo
Change in 6MWD from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in Six Minute Walk Distance (6MWD) Between DHEA and Placebo | 433.58 meters |
| Placebo to DHEA, Baseline | Change in Six Minute Walk Distance (6MWD) Between DHEA and Placebo | 355.2 meters |
| DHEA to placebo, 18 Weeks | Change in Six Minute Walk Distance (6MWD) Between DHEA and Placebo | 428.3 meters |
| Placebo to DHEA, 18 Weeks | Change in Six Minute Walk Distance (6MWD) Between DHEA and Placebo | 356.2 meters |
| DHEA to Placebo, 40 Weeks | Change in Six Minute Walk Distance (6MWD) Between DHEA and Placebo | 402.1 meters |
| Placebo to DHEA, 40 weeks | Change in Six Minute Walk Distance (6MWD) Between DHEA and Placebo | 364.6 meters |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.79generalized estimating equations (GEE)
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.34generalized estimating equations (GEE)
Secondary
Change in Testosterone, ng/dL
Change in Testosterone, ng/dL from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in Testosterone, ng/dL | 23.8 ng/dL |
| Placebo to DHEA, Baseline | Change in Testosterone, ng/dL | 10.2 ng/dL |
| DHEA to placebo, 18 Weeks | Change in Testosterone, ng/dL | 65.6 ng/dL |
| Placebo to DHEA, 18 Weeks | Change in Testosterone, ng/dL | 10.4 ng/dL |
| DHEA to Placebo, 40 Weeks | Change in Testosterone, ng/dL | 27 ng/dL |
| Placebo to DHEA, 40 weeks | Change in Testosterone, ng/dL | 35.3 ng/dL |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.002generalized estimating equations (GEE)
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: <0.0001generalized estimating equations (GEE)
Secondary
Change in World Health Organization (WHO) Functional Class
Change in WHO Functional Class (I - IV with IV indicating worse symptoms) between DHEA and placebo.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Change in World Health Organization (WHO) Functional Class | 2.2 score on a scale |
| Placebo to DHEA, Baseline | Change in World Health Organization (WHO) Functional Class | 2.3 score on a scale |
| DHEA to placebo, 18 Weeks | Change in World Health Organization (WHO) Functional Class | 2.2 score on a scale |
| Placebo to DHEA, 18 Weeks | Change in World Health Organization (WHO) Functional Class | 2.4 score on a scale |
| DHEA to Placebo, 40 Weeks | Change in World Health Organization (WHO) Functional Class | 2.1 score on a scale |
| Placebo to DHEA, 40 weeks | Change in World Health Organization (WHO) Functional Class | 2.3 score on a scale |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.33generalized estimating equations (GEE) w
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.99generalized estimating equations (GEE) w
Secondary
Cortisol, μg/dL^2
Change in Cortisol, μg/dL\^2 (micrograms per deciliter squared) from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Cortisol, μg/dL^2 | 11.7 μg/dL^2 |
| Placebo to DHEA, Baseline | Cortisol, μg/dL^2 | 9.1 μg/dL^2 |
| DHEA to placebo, 18 Weeks | Cortisol, μg/dL^2 | 9.2 μg/dL^2 |
| Placebo to DHEA, 18 Weeks | Cortisol, μg/dL^2 | 12.6 μg/dL^2 |
| DHEA to Placebo, 40 Weeks | Cortisol, μg/dL^2 | 12.9 μg/dL^2 |
| Placebo to DHEA, 40 weeks | Cortisol, μg/dL^2 | 11.7 μg/dL^2 |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.004generalized estimating equations
p-value: 0.05generalized estimating equations (GEE)
Secondary
Left Ventricular Ejection Fraction, %
Change in left ventricular ejection fraction (%) measured by Cardiac Magnetic Resonance Imaging (MRI). Change in LVEG from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging from the base of the heart through the apex was used.. Ventricular EFs are calculated by dividing respective stroke volumes (EDV-ESV) by EDVs. Normal Values: 56-78% for both males and females.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Left Ventricular Ejection Fraction, % | 66.2 % Change in LVEF |
| Placebo to DHEA, Baseline | Left Ventricular Ejection Fraction, % | 71.8 % Change in LVEF |
| DHEA to placebo, 18 Weeks | Left Ventricular Ejection Fraction, % | 69.1 % Change in LVEF |
| Placebo to DHEA, 18 Weeks | Left Ventricular Ejection Fraction, % | 71.4 % Change in LVEF |
| DHEA to Placebo, 40 Weeks | Left Ventricular Ejection Fraction, % | 68.4 % Change in LVEF |
| Placebo to DHEA, 40 weeks | Left Ventricular Ejection Fraction, % | 73.4 % Change in LVEF |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.33generalized estimating equations
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.23generalized estimating equations
Secondary
Left Ventricular End Diastolic Mass, g
Change in Left ventricular end diastolic mass, g measured by Cardiac Magnetic Resonance Imaging (MRI). Change in Left ventricular end diastolic mass, g from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging from the base of the heart through the apex. LV mass is determined at the end-diastole phase as the difference between end-diastolic epicardial and endocardial volumes X heart specific gravity (1.05 g/cm3).
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Left Ventricular End Diastolic Mass, g | 117.8 g |
| Placebo to DHEA, Baseline | Left Ventricular End Diastolic Mass, g | 119.3 g |
| DHEA to placebo, 18 Weeks | Left Ventricular End Diastolic Mass, g | 122.2 g |
| Placebo to DHEA, 18 Weeks | Left Ventricular End Diastolic Mass, g | 119.5 g |
| DHEA to Placebo, 40 Weeks | Left Ventricular End Diastolic Mass, g | 116.6 g |
| Placebo to DHEA, 40 weeks | Left Ventricular End Diastolic Mass, g | 114 g |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.55generalized estimating equations
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 1generalized estimating equations (GEE)
Secondary
Left Ventricular End-diastolic Volume (LVEDV) (mL)
Change in left ventricular LVEDV measured by Cardiac Magnetic Resonance Imaging (MRI). Change in LVEDV from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging was obtained from the base of the heart through the apex. The endocardial and epicardial borders of both ventricles are be traced manually on short axis cine images at end-diastole and end-systole with exclusion of the papillary muscles and trabeculae. EDV and ESV are calculated using Simpson's rule by summation of areas on each slice multiplied by the sum of slice thickness and image gap. Normal values (Male):77-195 ml. Normal values (female):58-154 ml.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Left Ventricular End-diastolic Volume (LVEDV) (mL) | 104.9 mL |
| Placebo to DHEA, Baseline | Left Ventricular End-diastolic Volume (LVEDV) (mL) | 109.9 mL |
| DHEA to placebo, 18 Weeks | Left Ventricular End-diastolic Volume (LVEDV) (mL) | 107.7 mL |
| Placebo to DHEA, 18 Weeks | Left Ventricular End-diastolic Volume (LVEDV) (mL) | 102.7 mL |
| DHEA to Placebo, 40 Weeks | Left Ventricular End-diastolic Volume (LVEDV) (mL) | 105.3 mL |
| Placebo to DHEA, 40 weeks | Left Ventricular End-diastolic Volume (LVEDV) (mL) | 101 mL |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.19generalized estimating equations (GEE)
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.94generalized estimating equations (GEE)
Secondary
Left Ventricular End-systolic Volume (LVESV) (mL)
Change in LVESV measured by Cardiac Magnetic Resonance Imaging (MRI). Change in LVEDV from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Short-axis steady state free precession (SSFP) imaging was obtained from the base of the heart through the apex. The endocardial and epicardial borders of both ventricles are be traced manually on short axis cine images at end-diastole and end-systole with exclusion of the papillary muscles and trabeculae. EDV and ESV are calculated using Simpson's rule by summation of areas on each slice multiplied by the sum of slice thickness and image gap. Normal Values (Female):13-51 ml. Normal values (Male):19-72 ml
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Left Ventricular End-systolic Volume (LVESV) (mL) | 31 mL |
| Placebo to DHEA, Baseline | Left Ventricular End-systolic Volume (LVESV) (mL) | 31.4 mL |
| DHEA to placebo, 18 Weeks | Left Ventricular End-systolic Volume (LVESV) (mL) | 32.7 mL |
| Placebo to DHEA, 18 Weeks | Left Ventricular End-systolic Volume (LVESV) (mL) | 30.5 mL |
| DHEA to Placebo, 40 Weeks | Left Ventricular End-systolic Volume (LVESV) (mL) | 32.5 mL |
| Placebo to DHEA, 40 weeks | Left Ventricular End-systolic Volume (LVESV) (mL) | 26.1 mL |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.62generalized estimating equations
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.39generalized estimating equations (GEE)
Secondary
Left Ventricular Stroke Volume (mL)
Change in Left ventricular stroke volume measured by Cardiac Magnetic Resonance Imaging (MRI). Change in Left ventricular stroke volume from baseline to 18 weeks (treatment period 1) and 18 week to 40 weeks (treatment period 2) in both groups: DHEA to Placebo (DHEA taken first, followed by washout and then Placebo) and Placebo to DHEA (placebo taken first, followed by washout and then DHEA). Stroke volume is calculated through breath-hold through-plane phase contrast imaging with a velocity encoding gradient (VENC) of \<120 cm/s (larger if aliasing present) in the main PA \ 2-3 cm above the pulmonary valve plane, with imaging plane oriented orthogonal to the main PA. Free-breathing phase contrast imaging in the same plane and VENC with averaging over 4 respiratory cycles.
Time frame: Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DHEA to Placebo, Baseline | Left Ventricular Stroke Volume (mL) | 72.8 mL |
| Placebo to DHEA, Baseline | Left Ventricular Stroke Volume (mL) | 78.4 mL |
| DHEA to placebo, 18 Weeks | Left Ventricular Stroke Volume (mL) | 74.0 mL |
| Placebo to DHEA, 18 Weeks | Left Ventricular Stroke Volume (mL) | 75.5 mL |
| DHEA to Placebo, 40 Weeks | Left Ventricular Stroke Volume (mL) | 71.5 mL |
| Placebo to DHEA, 40 weeks | Left Ventricular Stroke Volume (mL) | 72.2 mL |
Comparison: Treatment period 1: DHEA to Placebo group, change at 18 Weeks Treatment period 1: Placebo to DHEA group, change at 18 Weeksp-value: 0.33generalized estimating equations
Comparison: Treatment period 2: DHEA to Placebo group, change between 18 and 40 Weeks Treatment period 2: Placebo to DHEA group, change between 18 and 40 Weeksp-value: 0.88generalized estimating equations (GEE)
Secondary
Treatment-related Side Effects and Adverse Events
Treatment-related side effects and adverse events (as assessed by CTCAE v4.0). All participants in this trial received both DHEA and Placebo during the trial, therefore, side-effects and adverse events are listed according to the treatment or washout period in which they occurred.
Time frame: 18 weeks, 40 weeks
Population: Data shown as n (%) of all adverse events during DHEA, placebo or the washout period. Includes only events that occurred ≥ 2 times during the study. \*Specifically queried at each study visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Peripheral swelling | 0 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Headache | 1 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Rash | 0 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Hypokalemia | 2 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Diarrhea | 0 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Seborrhoea | 3 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Dry skin | 1 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Dizziness | 0 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Sepsis | 0 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Pruritis | 1 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Hair Growth | 2 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Catheter related infection | 2 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Hair Loss | 0 participants |
| DHEA to Placebo, Baseline | Treatment-related Side Effects and Adverse Events | Acne | 6 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Peripheral swelling | 1 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Acne | 0 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Catheter related infection | 2 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Seborrhoea | 1 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Hair Growth | 0 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Hair Loss | 2 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Headache | 0 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Diarrhea | 2 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Dizziness | 2 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Dry skin | 1 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Hypokalemia | 0 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Pruritis | 0 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Rash | 2 participants |
| Placebo to DHEA, Baseline | Treatment-related Side Effects and Adverse Events | Sepsis | 2 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Rash | 0 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Hypokalemia | 0 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Hair Loss | 0 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Hair Growth | 1 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Peripheral swelling | 1 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Seborrhoea | 1 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Acne | 0 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Pruritis | 1 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Catheter related infection | 0 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Dizziness | 0 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Diarrhea | 0 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Sepsis | 0 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Dry skin | 0 participants |
| DHEA to placebo, 18 Weeks | Treatment-related Side Effects and Adverse Events | Headache | 1 participants |