Auto-immunity and Pulmonary Arterial Hypertension (Auto-HTAP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01208792
First received: July 12, 2010
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

The investigators have recently evidenced the presence of antibodies to endothelial cells and fibroblasts in patients with idiopathic or SSc-associated PAH. The investigators also have identified several target antigens of anti-fibroblasts antibodies.

The objective of this study is to further investigate for the presence of antibodies to endothelial cells and fibroblasts in patients and characterize the antigen specificity of autoantibodies in patients with different types of non idiopathic and non SSc-associated PAH, such as PAH associated with HIV infection, porto-pulmonary hypertension, congenital heart diseases, systemic lupus erythematosus, mixed connective tissue disease and Sjögren's syndrome


Condition Intervention
Pulmonary Arterial Hypertension
HIV Infection
Congenital Heart Defect
Systemic Sclerosis
Connective Tissue Disease
Procedure: skin biopsy
Other: Blood Sample

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Auto-immunity and Prognosis of Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Immunological markers of prognosis interest in pulmonary arterial hypertension (PAH) [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Target antigens of autoantibodies [ Time Frame: one year ] [ Designated as safety issue: No ]
    To characterize target antigens of autoantibodies in non-idiopathic and non-SSc associated PAH and to compare these target antigens to those recognized by autoantibodies directed at endothelial cells, fibroblasts and vascular smooth muscle cells in patients with idiopathic and SSc-associated PAH;

  • Subpopulations of patients with PAH whose serum is able to induce the production of reactive oxygen species (ROS) [ Time Frame: one year ] [ Designated as safety issue: No ]
    • To study and characterize subpopulations of patients with PAH whose serum is able to induce the production of reactive oxygen species (ROS) and/or cell proliferation.
    • In patients in whom the whole serum induces cell proliferation and ROS production in cell cultures, to correlate the results of inhibition experiments in vivo in the presence of vasodilators used in the treatment of PAH and clinical response to these vasodilators


Estimated Enrollment: 650
Study Start Date: June 2010
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Disease group
Two hundred patients with PAH will be included: 50 patients with idiopathic PAH (iPAH), 20 with PAH associated with HIV infection, 20 with porto-pulmonary hypertension, 20 with PAH secondary to congenital heart disorders, 40 with SSc, 20 with SLE, 20 with MCTD and 10 with a PAH associated with a Sjögren's syndrome. Two hundred patients without PAH will also be included: 80 patients with SSc and 20 in each of the following groups: HIV infection, porto-pulmonary hypertension, SLE, congenital heart disorders, MCTD and with Sjögren's syndrome.
Procedure: skin biopsy
The biopsy site (usually the forearm) will be first cleaned, and then anesthetized with pain relieving (spray, cream, or injection). The skin is then sampled using a punch that takes a core (a small cylindrical fragment of tissue from the area of interest
Other Name: skin biopsy
Other: Blood Sample
a blood sample will be collected
Other Name: Blood Sample
Control group 1
Two hundred healthy blood donors age and sex-matched with patients with PAH, will be included as controls.
Other: Blood Sample
a blood sample will be collected
Other Name: Blood Sample
Control group 2
Twenty patients with proximal chronic thromboembolic pulmonary hypertension (CTPH) will also be included in a control arm of the study.
Other: Blood Sample
a blood sample will be collected
Other Name: Blood Sample

Detailed Description:

Two hundred and fifty patients with PAH will be included: 65 patients with idiopathic PAH (iPAH), 20 with PAH associated with HIV infection, 20 with porto-pulmonary hypertension, 20 with PAH secondary to congenital heart disorders, 40 with SSc, 20 with SLE, 20 with MCTD and 10 with a PAH associated with a Sjögren's syndrome.

Two hundred patients without PAH will also be included: 80 patients with SSc and 20 in each of the following groups: HIV infection, porto-pulmonary hypertension, SLE, congenital heart disorders, MCTD and with Sjögren's syndrome.

Twenty patients with proximal chronic thromboembolic pulmonary hypertension (CTPH) will also be included in a control arm of the study.

Two hundred and fifty healthy blood donors age and sex-matched with patients with PAH, will be included as controls.

By using 2D-immunoblotting techniques, we will evidence IgG antibodies to fibroblasts, EC, vascular smooth muscle cells (SMC) in multiple groups of patients and we will characterize target antigens of these autoantibodies. We will also assess the production of ROS: nitric oxide (NO), hydrogen peroxide (H2O2) and the effect of the whole serum (and the IgG particularly) on in VITRO proliferation of EC, fibroblasts and vascular SMC. For sera that will induce the production of ROS, we will study the effect of different vasodilatator (prostacycline, endothelin receptor antagonist, type 5 phosphodiesterase inhibitors) and anti-oxidant therapies.

Expected results We will characterize target antigens of autoantibodies of patients with non-idiopathic and non SSc-associated PAH. We will compare these target to those previously identified in idiopathic or SSc-associated PAH. We will then, distinguish subpopulations of PAH patients whose serum or purified IgG (possibly specific for a given antigen) are able to induce ROS production or cell proliferation. For the population of ROS-producer patients, we will correlate the clinical response to vasodilatator therapy to results of in VITRO inhibition experiments with vasodilatators and anti-oxidant molecules.

Perspectives The characterization of target antigens of EC, fibroblasts and vascular SMC specifically

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

age over 18

  • for PAH patients: pre-capillary PAH evidenced by right-heart catheterization
  • no associated systemic disease for idiopathic PAH patients
  • for HIV patients, HIV1 infection confirmed by ELISA and western blot
  • for patients with porto pulmonary hypertension: evidence by endoscopy of esophageal varices, confirmation of hepatic venous pressure gradient over 5 mmHg by catheterization of the hepatic veins
  • for patients with congenital heart defect: evidence by imaging of atrial or ventricular septal defect, or patent ductus arterious and confirmed by heart catheterization
  • patients with SSc will fulfill the American College of Rheumatology (ACR) and the LEROY and MEDSGER criteria
  • patients with MCTD will fulfill the criteria for MCTD
  • patients with SLE will fulfill the updated and revised ACR criteria
  • patients with Sjögren's syndrome will fulfill the American-European consensus group criteria
  • patients with chronic thromboembolic pulmonary hypertension: Lung scintiscan showing segmental mismatched perfusion defects and confirmation by angiography of the occlusion and the chance of success of endarterectomy according to the location of disease
  • Signed written informed consent
  • Patients with health insurance

Exclusion Criteria:

  • age under 18
  • pregnant women
  • absence of written informed consent
  • associated malignant tumor
  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: NCT01208792

Contacts
Contact: Luc Mouthon, MD, PHD +33(0)1 58 41 20 31 luc.mouthon@cch.aphp.fr
Contact: Raphaël Serreau, MD, PhD +33(0)1 58 41 11 80 raphael.serreau@cch.aphp.fr

Locations
France
Pneumology Department, Antoine Béclère Hospital Recruiting
Clamart, France, 92000
Internal Medicine Department, Claude Huriez Hospital Recruiting
Lille, France, 59000
Internal Medicine Department, Cochin Hospital Recruiting
Paris, France, 75014
Principal Investigator: Luc Mouthon, MD, PHD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Luc Mouthon, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01208792     History of Changes
Other Study ID Numbers: P071209
Study First Received: July 12, 2010
Last Updated: January 2, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Auto antibodies
Target antigens
2D-immunoblot
Reactive oxygen species
Pulmonary arterial hypertension
Systemic sclerosis
Human immunodeficiency virus infection
Porto pulmonary hypertension
Congenital heart defect
Systemic lupus erythematosus
Mixed connective tissue disease
Sjögren's syndrome

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Hypertension, Pulmonary
Connective Tissue Diseases
Heart Defects, Congenital
Hypertension
Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lung Diseases
Respiratory Tract Diseases
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Vascular Diseases
Skin Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 10, 2014