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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University Hospital, Bordeaux
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT00581087
First received: December 26, 2007
Last updated: December 31, 2013
Last verified: December 2013
  Purpose

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.)


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Hypertension, Pulmonary
Drug: DHEA treatment
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-blind, Randomised, Placebo-controlled Phase III Study of Dehydroepiandrosterone (DHEA) in Respiratory Pulmonary Hypertension in Adults

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • six-minute walk test [ Time Frame: inclusion and one year of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pulmonary and systemic arterial pressures (mean, systolic and diastolic) [ Time Frame: Inclusion and one after year of treatment ] [ Designated as safety issue: No ]
  • Pulmonary vascular resistances [ Time Frame: Inclusion and after one year of treatment ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: along one year of treatment ] [ Designated as safety issue: Yes ]
  • Compliance [ Time Frame: Along one year of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: January 2007
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
DHEA
Drug: DHEA treatment
DHEA : 200 mg/day hard gelatine capsule
Placebo Comparator: 2
Placebo
Drug: Placebo
Treatment : 200 mg/day hard gelatine capsule

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00581087

Contacts
Contact: Eric Dumas De La Roque, Dr eric.dumas-de-la-roque@chu-bordeaux.fr
Contact: Fabienne Nacka, PhD 06 74 43 54 48 fabienne.nacka@chu-bordeaux.fr

Locations
France
University Hospital, Bordeaux Recruiting
Bordeaux, France
Principal Investigator: Claire Dromer, Dr         
Sub-Investigator: Douard, Pr         
Sub-Investigator: Billes, Pr         
Sub-Investigator: Rean, Dr         
Sub-Investigator: Thambo, Dr         
Sub-Investigator: Dos Santos, Pr         
Sub-Investigator: Picard, Dr         
Sub-Investigator: Benissan, Pr         
Sub-Investigator: Bui, Dr         
APHP hospital Antoine Béclère GHU sud Recruiting
Clamart, France, 92141
Principal Investigator: Olivier Sitbon, Dr         
University Hospital, Limoges Recruiting
Limoges, France
Sub-Investigator: Melloni, Pr         
Principal Investigator: Dupuy-Grasset, Dr         
Sub-Investigator: Darodes, Dr         
Sub-Investigator: CASSAT, Dr         
Sub-Investigator: Vincent, Dr         
University Hospital, Strasbourg Recruiting
Strasbourg, France
Sub-Investigator: Stéphane Doutreleau, Dr         
Sub-Investigator: Weitzenblum, Pr         
Sub-Investigator: Canuet, Dr         
Sub-Investigator: Kraemer, Dr         
Principal Investigator: Enache, Dr         
University Hospital, Toulouse Recruiting
Toulouse, France
Sub-Investigator: Didier, Pr         
Sub-Investigator: Têtu, Dr         
Principal Investigator: Pontier, Dr         
Sub-Investigator: Prévot, Dr         
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Principal Investigator: Claire Dromer, Dr University Hospital, Bordeaux
Study Chair: Nicholas Moore, Pr Universty Hospital, Bordeaux
Study Director: Eric Dumas De La Roque, Dr University Hospital, Bordeaux
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT00581087     History of Changes
Other Study ID Numbers: Dromer, AFSSAPS 040479
Study First Received: December 26, 2007
Last Updated: December 31, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
Hypertension, pulmonary
DHEA
six-minute walk test
pulmonary arterial pressure

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Vascular Diseases
Cardiovascular Diseases
Respiratory Tract Diseases
Dehydroepiandrosterone
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014