Pulmonary Arterial Hypertension
Conditions
Keywords
idiopathic, heritable, anorexigen, PCH/PVOD
Brief summary
Pulmonary arterial hypertension (PAH), or high blood pressure in the lungs, is a rare condition that can shorten life. Although the cause of this disease is usually unknown, in about 70% of heritable and 15-20% of idiopathic cases there is a change in a gene (a mutation) that controls how blood vessels grow and function. The gene is called bone morphogenetic protein type receptor 2 (BMPR2). Although mutations in BMPR2 are a risk factor for PAH, not everyone with a mutation gets the disease. Additional genetic and environmental factors are likely to contribute. The investigators suspect that mutations in other genes are responsible for some cases of PAH. In this study the investigators aim to recruit all patients with PAH and some of their relatives and follow them up for several years. The investigators hope to discover new mutations for this disease and to determine what factors lead to poor outcome, and to understand what triggers disease in patients with mutations. Who can participate? Adults with PAH, their relatives and controls (one off blood sample)
Detailed description
What does the study involve? PAH patients will be seen at their local centre by their service team but they will have additional bloods taken. Relatives of PAH patients will be seen every year at their nearest PAH centre. Tests will include: * Epidemiology Questionnaire to assess factors affecting health * An echocardiogram (ECHO) to assess the size, shape, pumping action and the extent of any damage to the heart. * Lung function tests which include blowing measurements to assess gas volumes within the lungs as well as assessment of how the lungs exchange gases. * Optional right heart catheterisation (RHC) to determine how much blood your heart is pumping while you are resting and on exercise. Optional Cardiac Magnetic Resonance tests. To measure heart function. ( to be done only once) * 6 minute walk test. To measure exercise capacity * Cardiopulmonary exercise test. A bicycle exercise test, which will indicate how much blood your heart pumps while resting and with different levels of exercise. * Electrocardiogram (ECG), a test that measures the electrical activity of the heart * Blood tests Controls:Blood sample and medical data collected once
Interventions
None listed
Sponsors
British Heart Foundation
Medical Research Council
University of Cambridge
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
Inclusion Criteria-Patient * Participant is willing and able to give informed consent for participation in the study. * Male or Female, any age * Diagnosed with idiopathic, anorexigen-induced,heritable PAH, PVOD/PCH. Inclusion Criteria-Relative * Participant is willing and able to give informed consent for participation in the study. * Male or Female, any age * Has a family member diagnosed with idiopathic, anorexigen-induced, PVOD/PCH or heritable PAH
Exclusion criteria
-Patient The participant may not enter the study if ANY of the following apply: * Patient is unable to give informed consent. * Not suffering from idiopathic, anorexigen-induced, PVOD/PCH or heritable PAH
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To recruit a national cohort (1000 subjects) of heritable, idiopathic PAH and PVOD/PCH cases. | 8 years | The purpose of this study is to set up a national cohort of heritable, idiopathic PAH cases, PVOD/PCH and their relatives, to study the genetic and environmental contributions to disease. Setting up of this cohort of patients and relatives will provide the best resource for understanding what causes or triggers the disease, how to predict risk of death and response to therapy in individual patients, and to provide new ways of preventing and treating pulmonary arterial hypertension. The study will enable a better understanding for the first time the natural history of PAH, whether inherited or not. National outcomes to be measured will include survival, progression of the disease, changes in 6 minute walk distance, admissions to hospital for PAH and cause of death. Incidence of new cases of PAH will be measured in relatives as well. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To recruit PAH patients (1000) and family members to a Biorepository for serum/plasma and urine to identify biomarkers of disease onset, progression and response to treatment. | 8 years | To establish a Biorepository for serum/plasma, urine, tissues and cells from heritable pulmonary arterial hypertension (HPAH) patients, PVOD/PCH and their relatives, and patients with idiopathic PAH. This will allow studies to identify novel biomarkers of disease onset, progression and response to individual or combination therapies. |
Other
| Measure | Time frame | Description |
|---|---|---|
| longitudinal clinical evaluation and sampling of HPAH family members | 8 years | To characterise the natural history of disease onset and progression in the UK national cohort of PAH patients, coupled with longitudinal clinical evaluation and sampling of heritable pulmonary arterial hypertension family members. Longitudinal clinical data will be collated on subjects including haemodynamic data, clinical and research bloods, echocardiographic data, 6 minute walk distance, cardiopulmonary exercise testing, nt-proBNP and safety data ( admissions to hospital PAH related and cause and date of death) and medications. |
| Elucidation of the underlying genetic architecture of idiopathic and heritable PAH | 8 years | 1000 subjects will have a one off blood sample taken for next generation genetic sequencing (up to their entire genome). Samples will be sequenced to identify novel genetic mutations associated with PAH. A single blood sample will also be taken for mutation testing for BMPR2 and other genes associated with PAH. Outcomes will include identification of novel mutations in PAH |
Countries
United Kingdom
Contacts
Primary ContactNicholas Morrell
Backup ContactCarmen Treacy
Outcome results
None listed