Experimental design of the Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY) trial
| Autor: | Heather Morreo, Christopher J Mullin, Michael K. Atalay, Mary Whittenhall, Sruti Shiva, Thomas Walsh, Saurabh Agarwal, Daniel Arcuri, Brynn Normandin, Corey E. Ventetuolo, Grayson L. Baird, James R. Klinger |
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| Rok vydání: | 2020 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Dehydroepiandrosterone Vasodilation 030204 cardiovascular system & hematology right ventricle 03 medical and health sciences Diseases of the respiratory system 0302 clinical medicine Tar (tobacco residue) dehydroepiandrosterone Internal medicine pulmonary arterial hypertension polycyclic compounds Medicine Diseases of the circulatory (Cardiovascular) system sex Original Research Article RC705-779 business.industry clinical trial medicine.disease Pulmonary hypertension Clinical trial 030228 respiratory system RC666-701 Cardiology business |
| Zdroj: | Pulmonary Circulation Pulmonary Circulation, Vol 11 (2021) |
| ISSN: | 2045-8932 |
| Popis: | Pulmonary arterial hypertension (PAH) remains life-limiting despite numerous approved vasodilator therapies. Right ventricular (RV) function determines outcome in PAH but no treatments directly target RV adaptation. PAH is more common in women, yet women have better RV function and survival as compared to men with PAH. Lower levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester are associated with more severe pulmonary vascular disease, worse RV function, and mortality independent of other sex hormones in men and women with PAH. DHEA has direct effects on nitric oxide (NO) and endothelin-1 (ET-1) synthesis and signaling, direct antihypertrophic effects on cardiomyocytes, and mitigates oxidative stress. Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY) is an on-going randomized double-blind placebo-controlled crossover trial of DHEA in men ( n = 13) and pre- and post-menopausal women ( n = 13) with Group 1 PAH funded by the National Heart, Lung and Blood Institute. We will determine whether orally administered DHEA 50 mg daily for 18 weeks affects RV longitudinal strain measured by cardiac magnetic resonance imaging, markers of RV remodeling and oxidative stress, NO and ET-1 signaling, sex hormone levels, other PAH intermediate end points, side effects, and safety. The crossover design will elucidate sex-based phenotypes in PAH and whether active treatment with DHEA impacts NO and ET-1 biosynthesis. EDIPHY is the first clinical trial of an endogenous sex hormone in PAH. Herein we present the study’s rationale and experimental design. |
| Databáze: | OpenAIRE |
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