Effects of DHEA in Pulmonary Hypertension

NCT03648385 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: R01HL141268
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (8)

• 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.

  Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)

• 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.

  Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)

• †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.

  Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)

• 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.

  18 Weeks, 40 Weeks

• 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.

  Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)

• 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.

  Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)

• 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.

  Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)

• 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).

  18 weeks, 40 weeks

Secondary Outcomes (22)

• 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 World Health Organization (WHO) Functional Class

  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

  Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)

• Change in emPHasis-10

  Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)

• Change in NT-proBNP Between DHEA and Placebo

  Baseline to 18 weeks (treatment period 1), 18 weeks to 40 weeks (treatment period 2)

Study Arms (2)

DHEA to placebo

OTHER

DHEA tablet (50 mg) taken by mouth once a day for 18 weeks, followed by 4 week washout period and then 1 placebo tablet taken by mouth once a day for 18 weeks

Drug: DHEA tablet; Other: Placebo

Placebo to DHEA

OTHER

1 placebo tablet taken by mouth once a day for 18 weeks, followed by 4 week washout period and then 1 DHEA tablet taken by mouth once a day for 18 weeks

Drug: DHEA tablet; Other: Placebo

Interventions

DHEA tablet DRUG

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

Also known as: Dehydroepiandrosterone

DHEA to placebo; Placebo to DHEA

Placebo OTHER

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

DHEA to placebo; Placebo to DHEA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rhode Island Hospital: lead

Study Sites (1)

Rhode Island Hospital Pulmonary Hypertension Center

Providence, Rhode Island, 02903, United States

Location

Related Publications (1)

• Sanders R, Walsh T, Baird GL, Atalay MK, Agarwal S, Arcuri D, Klinger JR, Mullin CJ, Simmons J, Singh N, Whittenhall M, Ventetuolo CE. Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY): A Randomized, Double-Blind, Placebo-Controlled Crossover Trial. medRxiv [Preprint]. 2025 Aug 2:2025.08.01.25332627. doi: 10.1101/2025.08.01.25332627.

  PMID: 40766123 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Dehydroepiandrosterone

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 17-Ketosteroids; Ketosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Results Point of Contact

• Title: Corey Ventetuolo, MD
• Organization: Brown University Health, Center for Advanced Lung Care

corey_ventetuolo@brown.edu

401-444-2733

Study Officials

• Corey E Ventetuolo, MD, MS

  Brown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2018
• First Posted: August 27, 2018
• Study Start: January 9, 2019
• Primary Completion: June 24, 2024
• Study Completion: December 30, 2024
• Last Updated: November 5, 2025
• Results First Posted: November 5, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)