Ignite Creation Date:
2024-05-06 @ 12:34 AM
Last Modification Date:
2024-10-26 @ 10:51 AM
Study NCT ID:
NCT01600898
Status:
COMPLETED
Last Update Posted:
2021-01-13
First Post:
2012-05-15
Brief Title:
Screening of Pulmonary Arterial Hypertension in BMPR2 Mutation Carriers
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Screening and Risk Factors of Pulmonary Arterial Hypertension in BMPR2 Mutation Asymptomatic Carriers
Status:
COMPLETED
Status Verified Date:
2019-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DELPHI-2
Brief Summary:
In this prospective study the investigators will implement a systematic screening program and 3-year follow-up in a cohort of asymptomatic BMPR2 mutation carriers This study is designed to
determine predictive factors biological functional radiological and hemodynamic of development of PAH
monitor these subjects clinical functional biological echocardiographic and hemodynamic characteristics
assess the risk of occurrence of PAH
screen patients with PAH at an early stage of disease and offer them an early management
constitute a collection of biological samples 0 12 24 months follow-up of asymptomatic BMPR2 mutation carriers
determine predictive factors biological functional radiological and hemodynamic of development of PAH
monitor these subjects clinical functional biological echocardiographic and hemodynamic characteristics
assess the risk of occurrence of PAH
screen patients with PAH at an early stage of disease and offer them an early management
constitute a collection of biological samples 0 12 24 months follow-up of asymptomatic BMPR2 mutation carriers
Detailed Description:
Introduction
Pulmonary arterial hypertension is characterized by remodeling of small pulmonary arteries leading to a progressive increase in pulmonary vascular resistance resulting to right heart failure and ultimately death The disease is diagnosed when symptomatic demonstrating the existence of an already advanced form of the disease Indeed there is no simple tool allowing an early diagnosis of PAH and the disease is usually diagnosed in advanced stages Diagnostic confirmation of PAH is based on the elevation of mean pulmonary arterial pressures measured during right heart catheterization Despite the development of specific treatment in recent years PAH remains a disease with poor prognosis for which no cure is possible apart from lung transplantation in selected cases However recent studies have shown that specific drug therapy in early disease stages could improve the prognosis of this life threatening disease This is why it seems important to establish early diagnosis of PAH especially in high-risk populations such as asymptomatic carriers of BMPR2 Bone Morphogenetic Protein Receptor 2 mutations PAH due to BMPR2 mutations is an autosomal dominant disease with incomplete penetrance Even if there are no accurate data in the literature it is estimated that 20 of patients with BMPR2 mutations develop PAH in the course of their life The implementation of a genetic counseling in the National Reference Center for Severe Pulmonary Hypertension BICETRE Hospital allowed us to propose systematic assessment of BMPR2 mutations in patients with idiopathic or familial PAH In 2012 we identified 130 PAH patients carriers of a BMPR2 mutation This approach has enabled the detection of families at risk for PAH and to offer genetic counseling to the asymptomatic relatives with BMPR2 mutation However data on the evolution of asymptomatic carriers of BMPR2 mutation are lacking Furthermore there is no available consensus or guideline on how to follow this population To date it is not possible to differentiate asymptomatic subjects carrying BMPR2 mutations that will develop PAH from those who will never develop this disease However given the high risk of these subjects to develop PAH risk of 20 against 25million in the general population and the limited knowledge of characteristics of this population it seems essential to offer a prospective follow-up to this population at risk
Aim and objective
The main objective of this study to is follow prospectively for 3 years a cohort of asymptomatic carriers of BMPR2 mutation to
determine predictive factors biological functional radiological and hemodynamic of development of PAH
monitor these subjects clinical functional biological echocardiographic and hemodynamic characteristics
assess the risk of occurrence of PAH
screen patients with PAH at an early stage of disease and offer them an early management
constitute a collection of biological samples 0 12 24 months follow-up of asymptomatic BMPR2 mutation carriers
Methodology
Evaluation of subjects at inclusion after informed consent Ethics Committee approval obtained since 2011
Clinical evaluation dyspnea assessed by NYHA functional class I-IV signs of right heart failure
Chest radiograph electrocardiogram
Right heart catheterization in a subset of volunteers measurement of mean pulmonary artery pressure pulmonary artery occlusion pressure PAOP and cardiac output CO at rest and during exercise
Echocardiography measurement of the velocity of tricuspid regurgitation VIT measurement of TAPSE and Tei index pericardial effusion dilatation and hypertrophy of the right ventricle
Stress Test VO2 peak and VO2 specific VE minute ventilation VD VT dead space ventilatory reserve alveolar-arterial gradient pulse oxygen PaO2
Lung function tests measurement of DLCO and DLNO
Magnetic resonance imaging MRI measuring end systolic diastolic volumes of the right ventricle right ventricular mass septal curvature diameter of the pulmonary arteries surface of the right atrium
Biology Determination of plasma NT-proBNP uric acid serum sodium creatinine PDGF ET-1 ET-3 CRPus IL-6 soluble c-kit CXCL12 progenitors and circulating fibrocytes
Subjects will be evaluated as outpatients scheduled to the National Reference Center for Severe Pulmonary Hypertension 12 24 and 36 months after inclusion or if symptoms appear dyspnoea right heart failure malaise or syncope
During these consultations the assessment will include clinical evaluation chest radiograph electrocardiogram echocardiogram stress testing pulmonary function tests magnetic resonance imaging and biology
To confirm the suspicion of PAH and assess their severity right heart catheterization at rest and during exercise will be offered according to a decision algorithm
Right heart catheterization will be performed if one of the following abnormalities is found
Dyspnea malaise or unexplained syncope
Tricuspid regurgitation velocity 28 m s
Decrease of the specific peak VO2 20 as compared to the gold standard
If diagnosis of PAH is confirmed patients will be treated according to the recently updated recommendations of the European Respiratory Society and European Society of Cardiology
Pulmonary arterial hypertension is characterized by remodeling of small pulmonary arteries leading to a progressive increase in pulmonary vascular resistance resulting to right heart failure and ultimately death The disease is diagnosed when symptomatic demonstrating the existence of an already advanced form of the disease Indeed there is no simple tool allowing an early diagnosis of PAH and the disease is usually diagnosed in advanced stages Diagnostic confirmation of PAH is based on the elevation of mean pulmonary arterial pressures measured during right heart catheterization Despite the development of specific treatment in recent years PAH remains a disease with poor prognosis for which no cure is possible apart from lung transplantation in selected cases However recent studies have shown that specific drug therapy in early disease stages could improve the prognosis of this life threatening disease This is why it seems important to establish early diagnosis of PAH especially in high-risk populations such as asymptomatic carriers of BMPR2 Bone Morphogenetic Protein Receptor 2 mutations PAH due to BMPR2 mutations is an autosomal dominant disease with incomplete penetrance Even if there are no accurate data in the literature it is estimated that 20 of patients with BMPR2 mutations develop PAH in the course of their life The implementation of a genetic counseling in the National Reference Center for Severe Pulmonary Hypertension BICETRE Hospital allowed us to propose systematic assessment of BMPR2 mutations in patients with idiopathic or familial PAH In 2012 we identified 130 PAH patients carriers of a BMPR2 mutation This approach has enabled the detection of families at risk for PAH and to offer genetic counseling to the asymptomatic relatives with BMPR2 mutation However data on the evolution of asymptomatic carriers of BMPR2 mutation are lacking Furthermore there is no available consensus or guideline on how to follow this population To date it is not possible to differentiate asymptomatic subjects carrying BMPR2 mutations that will develop PAH from those who will never develop this disease However given the high risk of these subjects to develop PAH risk of 20 against 25million in the general population and the limited knowledge of characteristics of this population it seems essential to offer a prospective follow-up to this population at risk
Aim and objective
The main objective of this study to is follow prospectively for 3 years a cohort of asymptomatic carriers of BMPR2 mutation to
determine predictive factors biological functional radiological and hemodynamic of development of PAH
monitor these subjects clinical functional biological echocardiographic and hemodynamic characteristics
assess the risk of occurrence of PAH
screen patients with PAH at an early stage of disease and offer them an early management
constitute a collection of biological samples 0 12 24 months follow-up of asymptomatic BMPR2 mutation carriers
Methodology
Evaluation of subjects at inclusion after informed consent Ethics Committee approval obtained since 2011
Clinical evaluation dyspnea assessed by NYHA functional class I-IV signs of right heart failure
Chest radiograph electrocardiogram
Right heart catheterization in a subset of volunteers measurement of mean pulmonary artery pressure pulmonary artery occlusion pressure PAOP and cardiac output CO at rest and during exercise
Echocardiography measurement of the velocity of tricuspid regurgitation VIT measurement of TAPSE and Tei index pericardial effusion dilatation and hypertrophy of the right ventricle
Stress Test VO2 peak and VO2 specific VE minute ventilation VD VT dead space ventilatory reserve alveolar-arterial gradient pulse oxygen PaO2
Lung function tests measurement of DLCO and DLNO
Magnetic resonance imaging MRI measuring end systolic diastolic volumes of the right ventricle right ventricular mass septal curvature diameter of the pulmonary arteries surface of the right atrium
Biology Determination of plasma NT-proBNP uric acid serum sodium creatinine PDGF ET-1 ET-3 CRPus IL-6 soluble c-kit CXCL12 progenitors and circulating fibrocytes
Subjects will be evaluated as outpatients scheduled to the National Reference Center for Severe Pulmonary Hypertension 12 24 and 36 months after inclusion or if symptoms appear dyspnoea right heart failure malaise or syncope
During these consultations the assessment will include clinical evaluation chest radiograph electrocardiogram echocardiogram stress testing pulmonary function tests magnetic resonance imaging and biology
To confirm the suspicion of PAH and assess their severity right heart catheterization at rest and during exercise will be offered according to a decision algorithm
Right heart catheterization will be performed if one of the following abnormalities is found
Dyspnea malaise or unexplained syncope
Tricuspid regurgitation velocity 28 m s
Decrease of the specific peak VO2 20 as compared to the gold standard
If diagnosis of PAH is confirmed patients will be treated according to the recently updated recommendations of the European Respiratory Society and European Society of Cardiology
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| AOM 10175 | OTHER | PHRC 2010 | None |