Effects of DHEA in Pulmonary Hypertension (EDIPHY)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: DHEA tablet; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Britt Ferland; Phone Number: 401-444-4961; Email: bselland@lifespan.org
• Study Contact Backup: Name: Rachel Sanders; Phone Number: 401-444-2733; Email: rsanders1@lifespan.org

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital Pulmonary Hypertension Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Rhode Island Hospital
• Investigators: Principal Investigator: Corey E Ventetuolo, MD, MS, Brown University

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2019
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 10, 2018
• First Submitted That Met QC Criteria: August 23, 2018
• First Posted (Actual): August 27, 2018

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Dehydroepiandrosterone
• Other Study ID Numbers: R01HL141268 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No