Study of Dehydroepiandrosterone (DHEA) in Respiratory Pulmonary Hypertension in Adults
Study of Dehydroepiandrosterone (DHEA) in Respiratory Pulmonary Hypertension in Adults
DHEA prevents and reverses chronic hypoxic pulmonary hypertension in a chronic
 hypoxic-pulmonary hypertension model in the rat. However, no study has been performed in
 human. The purpose of this study is to determine if DHEA is effective in the treatment of
 respiratory pulmonary hypertension in adults with Chronic Obstructive Pulmonary Disease
 (COPD) on exercise capacity and haemodynamic variables. Patients will receive after
 randomization either 200 mg oral DHEA or placebo over a one-year period. Evaluation concerns
 clinical parameters, echocardiography and right catheterization after and before treatment.
 Primary end-point is the six-minute walk test. This is a prospective double blind,
 randomized, placebo controlled study which will be realized in four university hospitals in
 France : Bordeaux, Strasbourg, Toulouse and Limoges.

 Eight patients with pulmonary hypertension (New York Heart Association functional class III
 or IV) associated with COPD were included in a pilot study between 2004 and 2005. Inclusion
 criteria were: COPD was defined by FEV1/FVC < 70% of reference values; resting mean pulmonary
 artery pressure (assessment by right pulmonary catheterization) ≥ 25mmHg with mean pulmonary
 capillary wedge pressure ≤ 15mmHg, PaO2 ≤ 60mmHg at rest or PaO2 ≥ 60mmHg associated with
 significant fall in O2 saturation with exercise; oxygen treatment initiated more than six
 months previously. Exclusion criteria were: clinical or respiratory instability during the
 three months before the inclusion in the study; corticosteroids therapy (> 0.5mg/kg/day of
 prednisolone or as equivalent); hepatic (prothrombin time < 50%) or renal (creatininemia >
 130µmol/L) failure; diabetes; left ventricular dysfunction; PSA (prostatic antigens >
 2,5ng/ml) and past history or diagnosis of cancer. The study was conducted in accordance with
 the Good Clinical Practices Guidelines. The study protocol was approved by the ethics review
 board of the University Hospital of Bordeaux (France). Written informed consent was obtained
 for all patients and investigations were conducted according to the institutional guidelines
 and to the Helsinki principles. This trial conducted enrollment between 2004 and 2005, but
 had not been registered in ClinicalTrials.gov because it preceded this policy.(Study design:
 The dose of oral DHEA administered was 200 mg once daily for three months. At baseline and
 after three months of treatment, clinical evaluation included 6MWT, Borg dyspnea index,
 systolic and diastolic blood pressure, right heart catheterisation, lung function testing and
 serum DHEA levels were performed.)
• Principal Objective : Efficacy of DHEA on exercise capacity (six-minute walk test)

 -  Secondary Objective :

 -  Efficacy of DHEA on pulmonary arterial pressures (mean, systolic and diastolic), on
 systemic arterial pressures, pulmonary vascular resistances

 -  Safety of DHEA treatment

 -  Observance of treatment by DHEA

 -  Study design :

 Double-blind, randomized, placebo-controlled Phase III study. Patients will be randomized
 into two parallel groups to receive either 200 mg oral DHEA or placebo over a one-year
 treatment. This is a multicentric study in the departments of respiratory medicine of
 Bordeaux, Strasbourg, Limoges and Toulouse (France).

 • Inclusion criteria :

 -  Age ≥ 18 years old and ≤ 75 years old (*)

 -  Chronic Obstructive Pulmonary Disease with VEMS/CV < 70% ( **)

 -  Respiratory pulmonary hypertension with mean pulmonary arterial pressure ≥ 25 mmHg (**)
 related to normal pulmonary capillary pressure assessed by catheterization of the right
 side of the heart (pulmonary capillary wedge pressure ≤12mmHg)

 -  PO2 ≤ 60 mmHg assessed by arterial gazometry at ease (**) or PO2 > 60 mmHg, but related
 with high hypoxemia after exercise (six-minute walk test )

 -  Oxygenotherapy more than 6 months before pre-screening

 -  Written informed consent

 (*) Inclusion of young adults concerns COPD related to asthma or cystic fibrosis (**)
 Criteria assessed from last health check or the last exams for COPD diagnosis

 -  Exclusion criteria :

 -  Clinical instability and/or respiratory exacerbation within the previous three
 months

 -  Clinical instability and/or respiratory exacerbation dangerous for catheterization

 -  Pregnancy (ßHCG > 20 UI /l) or breastfeeding on going

 -  General corticotherapy > 0,5 mg/kg/j prédnisolone equivalent

 -  Hepatic insufficiency (TP < 50%) or renal insufficiency (creatininemia > 130
 µmol/l) or diabetes mellitus type I or II (treated by oral antidiabetic oral or
 insulin)

 -  Left-heart failure (coronary heart disease and/or left valvulopathy)

 -  High level of prostatic specific antigen (PSA) (> 2,5ng/ml)

 -  Previous cancer or treatment on going

 -  Study plan:

 After the screening evaluation and written consent document, patients will be randomized into
 two groups placebo or DHEA, over a one year treatment.

 • Number of subjects : 60 patients based on the increase of 30 % of the primary end-point,
 (six-minute walk test), i.e., 30 patients will be included in each group.
Inclusion Criteria:

 -  Age ≥ 18 years old and ≤ 75 years old (*)

 -  Chronic Obstructive Pulmonary Disease with FEVs/VC < 70% (**)

 -  Respiratory pulmonary hypertension with mean pulmonary arterial pressure ≥ 25 mmHg
 (**) related to normal pulmonary capillary pressure assessed by catheterization of the
 right side of the heart (pulmonary capillary wedge pressure ≤12mmHg)

 -  PO2 ≤ 60 mmHg assessed by arterial gazometry at ease (**) or PO2 > 60 mmHg, but
 related with high hypoxemia after exercise (six-minute walk test )

 -  Oxygenotherapy more than 6 months before pre-screening

 -  Written informed consent

 (*) Inclusion of young adults concerns COPD related to asthma or cystic fibrosis (**)
 Criteria assessed from last health check or the last exams for COPD diagnosis

 Exclusion Criteria:

 -  clinical instability and/or respiratory exacerbation within the previous three months

 -  clinical instability and/or respiratory exacerbation dangerous for catheterization

 -  Pregnancy (ßHCG > 20 UI /l) or breastfeeding on going

 -  General corticotherapy > 0,5 mg/kg/day prédnisolone equivalent

 -  Hepatic insufficiency (TP < 50%) or renal insufficiency (creatininemia > 130 µmol/l)
 or diabetes mellitus type I or II (treated by oral antidiabetic or insulin)

 -  Left-heart failure (coronary heart disease and/or left valvulopathy)

 -  High level of prostatic specific antigen (PSA) (> 2,5ng/ml)

 -  Cancer antecedent or treatment on going