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

NCT00581087 | Unknown Phase 3

• 2 other identifiers: DromerAFSSAPS 040479
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

Brief 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.)

Conditions

Chronic Obstructive Pulmonary Disease; Hypertension, Pulmonary

Keywords

Hypertension, pulmonary; DHEA; six-minute walk test; pulmonary arterial pressure

Outcome Measures

Primary Outcomes (1)

• six-minute walk test

  inclusion and one year of treatment

Secondary Outcomes (4)

• 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

Study Arms (2)

1

EXPERIMENTAL

DHEA

Drug: DHEA treatment

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

DHEA treatment DRUG

DHEA : 200 mg/day hard gelatine capsule

1

Placebo DRUG

Treatment : 200 mg/day hard gelatine capsule

2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (5)

University Hospital, Bordeaux

Bordeaux, France

Location

APHP hospital Antoine Béclère GHU sud

Clamart, 92141, France

Location

University Hospital, Limoges

Limoges, France

Location

University Hospital, Strasbourg

Strasbourg, France

Location

University Hospital, Toulouse

Toulouse, France

Location

Related Publications (2)

• Bonnet S, Dumas-de-La-Roque E, Begueret H, Marthan R, Fayon M, Dos Santos P, Savineau JP, Baulieu EE. Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9488-93. doi: 10.1073/pnas.1633724100. Epub 2003 Jul 23.

  PMID: 12878719 BACKGROUND

• Dumas de La Roque E, Savineau JP, Metivier AC, Billes MA, Kraemer JP, Doutreleau S, Jougon J, Marthan R, Moore N, Fayon M, Baulieu EE, Dromer C. Dehydroepiandrosterone (DHEA) improves pulmonary hypertension in chronic obstructive pulmonary disease (COPD): a pilot study. Ann Endocrinol (Paris). 2012 Feb;73(1):20-5. doi: 10.1016/j.ando.2011.12.005. Epub 2012 Jan 26.

  PMID: 22280813 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Claire Dromer, Dr

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Nicholas Moore, Pr

  Universty Hospital, Bordeaux

  STUDY CHAIR

• Eric Dumas De La Roque, Dr

  University Hospital, Bordeaux

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: December 27, 2007
• Study Start: January 1, 2007
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: January 14, 2015

Record last verified: 2015-01

Locations

FR (5)