Effects of DHEA in Pulmonary Hypertension (EDIPHY)

• ClinicalTrials.gov Identifier: NCT03648385
• Recruitment Status: Recruiting
• First Posted: August 27, 2018
• Last Update Posted: March 29, 2022
• Sponsor: Rhode Island Hospital
• Information provided by (Responsible Party): Rhode Island Hospital

Tracking Information

• First Submitted Date: August 10, 2018
• First Posted Date: August 27, 2018
• Last Update Posted Date: March 29, 2022
• Actual Study Start Date: January 9, 2019
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2018)

Right ventricular (RV) longitudinal strain [ Time Frame: 18 weeks, 40 weeks ]

Change in global RV longitudinal strain measured by cardiac magnetic resonance imaging (MRI) between DHEA and placebo

Original Primary Outcome Measures (submitted: August 23, 2018)

Right ventricular (RV) longitudinal strain [ Time Frame: 18 weeks, 40 weeks ]

Difference in global RV longitudinal strain measured by cardiac magnetic resonance imaging (MRI) between DHEA and placebo

Current Secondary Outcome Measures (submitted: August 27, 2018)

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

Original Secondary Outcome Measures (submitted: August 23, 2018)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effects of DHEA in Pulmonary Hypertension
• Official Title: Effects of DHEA in Pulmonary Hypertension
• 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 compared to placebo and to assess side effects and safety in pulmonary arterial hypertension.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Pulmonary Arterial Hypertension

Intervention

• Drug: DHEA tablet
  DHEA tablet (50 mg) taken by mouth once a day for 18 weeks.
  Other Name: Dehydroepiandrosterone
• Other: Placebo
  1 placebo tablet taken by mouth once a day for 18 weeks

Study Arms

• Experimental: DHEA
  DHEA tablet (50 mg) taken by mouth once a day for 18 weeks
  Intervention: Drug: DHEA tablet
• Placebo Comparator: Placebo
  1 placebo tablet taken by mouth once a day for 18 weeks
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 23, 2018): 24
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2023
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Diagnosis of PAH that is 1) idiopathic, 2) heritable or 3) associated with connective tissue disease, congenital systemic-to-pulmonary shunt, porto-pulmonary hypertension, drug or toxin use.

Documentation of the following at any time prior to study entry:

• mPAP ≥ 25 mmHg at rest, pulmonary capillary wedge pressure or left ventricular end-diastolic pressure ≤ 15 mmHg, and PVR > 3 Wood units
• Pulmonary function testing documenting forced expiratory volume in one second/forced vital capacity ratio ≥ 70% predicted and total lung capacity ≥ 70% predicted
• If TLC is mildly reduced (60%<TLC%<70%), computerized tomography (HRCT or non-HRCT) documenting no significant interstitial lung disease may be used to fulfill this requirement.
• Chest tomography documenting no more than moderate parenchymal lung disease with clinician designated WHO I PAH and meeting both TLC and FEV1/FVC criteria.
• Normal or low probability V/Q scan
• If no V/Q scan is available, a CT angiogram documenting the absence of thromboembolic disease may be used, provided the subject meets diagnostic PAH criteria

Exclusion Criteria:

• Age < 18 years old
• PAH associated with human immunodeficiency virus infection
• New background PAH therapy within 12 weeks
• Significant dose change in background PAH therapy within 12 weeks.
• Untreated severe obstructive sleep apnea diagnosed by polysomnography
• Evidence of left-sided valvular disease or systolic dysfunction on echocardiogram (≥ moderate mitral or aortic disease or LV ejection fraction ≤ 50%)
• Glomerular filtration rate <40 mls/min/1.73m2
• Child-Pugh Class C cirrhosis
• Untreated hypo- or hyper-thyroidism
• Pregnant or breastfeeding
• Active or planned use of hormone supplements, oral contraceptive pills, hormonal therapies
• History of breast, ovarian, uterine, testicular or prostate cancer
• Current use of another investigational PAH therapy
• Contraindication to MRI (e.g., metal device or fragment)
• History of significant non-adherence or circumstance which would threaten ability to comply with cross-over design and study visit schedule

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Thomas Walsh; 401-444-4833; thomas.walsh@lifespan.org

Contact: Ryan DiGregorio; 401-444-2733; rdigregorio@lifespan.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03648385
• Other Study ID Numbers: R01HL141268( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Rhode Island Hospital
• Study Sponsor: Rhode Island Hospital
• Collaborators: Not Provided

Investigators

• Principal Investigator: Corey E Ventetuolo, MD, MS; Brown University

• PRS Account: Rhode Island Hospital
• Verification Date: January 2022