Study of Dehydroepiandrosterone (DHEA) in Respiratory Pulmonary Hypertension in Adults

Study Overview
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Brief Summary
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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.)

Detailed Description
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• 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.

Official Title
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Double-blind, Randomised, Placebo-controlled Phase III Study of Dehydroepiandrosterone (DHEA) in Respiratory Pulmonary Hypertension in Adults

Conditions
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Chronic Obstructive Pulmonary Disease, Hypertension, Pulmonary

Intervention / Treatment
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* Drug: DHEA treatment
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>DHEA | Drug: DHEA treatment<br>* DHEA : 200 mg/day hard gelatine capsule<br>|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Treatment : 200 mg/day hard gelatine capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| six-minute walk test |  | inclusion and one year of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary and systemic arterial pressures (mean, systolic and diastolic) |  | Inclusion and one after year of treatment | 
| Pulmonary vascular resistances |  | Inclusion and after one year of treatment | 
| Safety |  | along one year of treatment | 
| Compliance |  | Along one year of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, pulmonary, DHEA, six-minute walk test, pulmonary arterial pressure