Condition category
Circulatory System
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status

Plain English Summary

Background and study aims
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 cases with unknown cause there is a change in a gene (a mutation) that controls how blood vessels grow and function. The gene is called BMPR2. Although mutations in BMPR2 are a risk factor for high blood pressure in the lungs, not everyone with a mutation gets the disease. Additional genetic and environmental factors are likely to contribute. We suspect that mutations in other genes are responsible for some cases. In this study we aim to recruit patients and follow them up for several years. We hope to discover new mutations for this disease and to find out what factors lead to poor outcome, and to understand what triggers disease in patients with mutations.

Who can participate?
Adults with high blood pressure in the lungs and their relatives can participate in this study.

What does the study involve?
Subjects are enrolled into a national study. Patients will be seen at their routine follow-up and have additional blood and urine samples. Relatives will be seen every 6 months and have tests, blood and urine samples.

What are the possible benefits and risks of participating?
It is not known whether you will gain any personal benefit from this research. However, information from this study could improve our understanding of the disease and help doctors to treat patients better in the future.

Where is the study run from?
The study will be run from all pulmonary hypertension centres in the UK and Dublin, Ireland.

When is the study starting and how long is it expected to run for?
The study is expected to start in September 2013 and will run for at least 5 years.

Who is funding the study?
The British Heart Foundation (UK) and Medical Research Council (MRC), UK.

Who is the main contact?
Professor Nicholas Morrell
Tel: 01223 331666

Trial website

Contact information



Primary contact

Prof Nicholas Morrell


Contact details

University of Cambridge
Department of Medicine
Box 157 Addenbrooke’s Hospital
Hills Road
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title



Study hypothesis

Idiopathic and heritable forms of pulmonary arterial hypertension (PAH) are devastating conditions associated with high morbidity and mortality. The disease is usually diagnosed late by finding a markedly increase mean pulmonary arterial pressure, the result of progressive narrowing and remodeling of the pulmonary vasculature, and leading to the failure of the right ventricle. This disease tends to present in the middle decades of life, with a female predominance (f:m 2.3:1). Untreated, it carries a 3 year mortality of 60%. A major breakthrough in our understanding of the pathobiology of PAH was the identification of heterozygous disease causing mutations in the gene coding the bone morphogenetic protein type 2 receptor (BMPR2) in families with PAH. Although research over the last 10 years has provided important clues, the precise cellular and molecular mechanisms leading to the disease manifestation remain incompletely understood. In addition, the penetrance of this mutation in families is low, on average approximately 20%. The existence of discordant monozygotic twins points to the presence of important environmental factors. A further 15-26% of apparently sporadic cases of idiopathic PAH harbour mutations in BMPR2. Data is now emerging that patients with mutations present earlier and die of their disease at an earlier age than patients without BMPR2 mutations. The exact aetiology remains unknown and patients appear to progress at different rates, and respond differently to existing treatments. This study will provide a more complete understanding of the aetiology and natural history of idiopathic and heritable PAH from a detailed analysis of their genetic influences and the contribution of potential environmental factors, linked to deep phenotyping of a national cohort. Identification of the critical environmental and additional genetic factors leading to the disease manifestation in PAH will lead to strategies for disease prevention and may identify pathways for the development of novel therapies, and provide a basis for mechanistic studies in vitro and in vivo.

Funding has been awarded from the British Heart Foundation and the Medical Research Council to establish and maintain a UK & Ireland cohort study of heritable and idiopathic pulmonary arterial hypertension (March 2013-2018). The purpose of this study is to set up a national cohort study of patients with idiopathic PAH, and PAH due to mutations in BMPR2. Family members with and without BMPR2 mutations will also be studied. The identification and follow up of patients with and without BMPR2 mutations, and possibly other mutations, will provide important information on the clinical course of genetic causes of PAH. It will also provide a platform for the identification of novel genetic variation in the BMPR2 negative patients. The longitudinal follow up and sampling of unaffected BMPR2 mutation carriers, and mutation negative family members, will provide information on penetrance, and whether different mutations confer specific risks. In addition, the cohort will provide samples for hypothesis driven studies to ascertain genetic or environmental triggers for this disease. The cohort will further provide a basis for future research and prevention studies or experimental medicine interventions targeting the BMPR2 pathway. Patients and relatives will be screened for the BMPR2 mutation before recruitment into to the study. They will be followed up every 6 months with for sampling and clinical assessment and data will be collected and semi-anonymised.

Ethics approval

NRES Committee East of England-Hatfeild, REC reference:13/EE/0203, approval pending

Study design

Multicentre observational cohort study

Primary study design


Secondary study design

Cohort study

Trial setting

Not specified

Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient or relative patient information sheet
Professor Nick Morrell, Tel: 01223 331666,


Idiopathic, heritable and anorexigen pulmonary arterial hypertension


PAH patients will be seen at their local centre by their service team but they will have additional bloods and urine samples taken. Relatives of PAH patients will be seen every 6 months at their nearest PAH centre. Subjects will be seen for up to 5 years depending on when they are recruited in to the study. Tests will include:

1. CAMPHOR questionnaire to assess your quality of life
2. Epidemiology Questionnaire to assess factors affecting health
3. An echocardiogram (ECHO) to assess the size, shape, pumping action and the extent of any damage to the heart.
4. Lung function tests which include blowing measurements to assess gas volumes within the lungs as well as assessment of how the lungs exchange gases.
5. 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. Six minute walk test. To measure exercise capacity
7. Cardiopulmonary exercise test. A bicycle exercise test, which will indicate how much blood your heart pumps while resting and with different levels of exercise.
8. Electrocardiogram (ECG), a test that measures the electrical activity of the heart
9. Blood tests
10. Urine

Intervention type



Not Applicable

Drug names

Primary outcome measure

Recruitment of significant numbers of cases of heritable and idiopathic PAH to the cohort.

Measured at 5 years

Secondary outcome measures

1. Recruitment of significant numbers of relatives of patients with HPAH for follow up.
2. Identification of novel causal genetic variation underlying heritable and idiopathic PAH.
3. Identification of novel biomarkers of disease progression or response to therapy from patient samples
4. Identification of potential environmental triggers of disease from epidemiological studies

Outcomes measured at 5 years

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Participant is willing and able to give informed consent for participation in the study.
2. Male or Female, aged 16-80 years
3. Diagnosed with idiopathic, anorexigen-induced or heritable PAH.

1. Participant is willing and able to give informed consent for participation in the study.
2. Male or Female, aged 16-80 years
3. Has a family member diagnosed with idiopathic, anorexigen-induced, or heritable PAH

Participant type


Age group




Target number of participants


Participant exclusion criteria

The participant may not enter the study if ANY of the following apply:
1. Patient is unable to give informed consent.
2. Not suffering from idiopathic, anorexigen-induced, or heritable PAH

The participant may not enter the study if ANY of the following apply:
1. Patient is unable to give informed consent

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

University of Cambridge
United Kingdom

Sponsor information


Cambridge University Hospitals NHS Foundation Trust (UK)

Sponsor details

c/o Mr Stephen Keller
Research and Development Department
Box 277 Addenbrookes Hospital
Hills Road
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type


Funder name

British Heart Foundation (UK)

Alternative name(s)


Funding Body Type

private sector organisation

Funding Body Subtype



United Kingdom

Funder name

Medical Research Council (MRC) (UK)

Alternative name(s)


Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government


United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes