Overview

This trial is active, not recruiting.

Conditions chronic obstructive pulmonary disease, hypertension, pulmonary
Treatments dhea treatment, placebo
Phase phase 3
Sponsor University Hospital, Bordeaux
Start date January 2007
End date June 2015
Trial size 60 participants
Trial identifier NCT00581087, AFSSAPS 040479, Dromer

Summary

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.)

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
DHEA
dhea treatment
DHEA : 200 mg/day hard gelatine capsule
(Placebo Comparator)
Placebo
placebo
Treatment : 200 mg/day hard gelatine capsule

Primary Outcomes

Measure
six-minute walk test
time frame: inclusion and one year of treatment

Secondary Outcomes

Measure
Pulmonary and systemic arterial pressures (mean, systolic and diastolic)
time frame: Inclusion and one after year of treatment
Pulmonary vascular resistances
time frame: Inclusion and after one year of treatment
Safety
time frame: along one year of treatment
Compliance
time frame: Along one year of treatment

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

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

Additional Information

Official title Double-blind, Randomised, Placebo-controlled Phase III Study of Dehydroepiandrosterone (DHEA) in Respiratory Pulmonary Hypertension in Adults
Principal investigator Claire Dromer, Dr
Description • 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.
Trial information was received from ClinicalTrials.gov and was last updated in January 2015.
Information provided to ClinicalTrials.gov by University Hospital, Bordeaux.