National Cohort Study of Idiopathic and Heritable Pulmonary Arterial Hypertension (NAIAD)

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)

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Arterial Hypertension

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

• Study Type: Observational
• Enrollment (Anticipated): 3600

Contacts and Locations

• Study Contact: Name: Nicholas Morrell; Phone Number: 01223 331666; Email: nwm23@cam.ac.uk
• Study Contact Backup: Name: Carmen Treacy; Phone Number: 1223 763094; Email: cohortcoordination@medschl.cam.ac.uk

Study Locations

• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • Recruiting
    • Royal United Hospitals Bath
    • Contact: Robert MacKenenzie Ross, PI
  • Cambridge, United Kingdom
    • Recruiting
    • Royal Papworth Hospital NHS Trust
    • Principal Investigator: Joanna Pepke-Zaba
  • Glasgow, United Kingdom
    • Recruiting
    • Golden Jubilee National Hospital
    • Principal Investigator: Colin Church
  • London, United Kingdom
    • Recruiting
    • Royal Free Hospital
    • Principal Investigator: Gerry Goglan
  • London, United Kingdom
    • Recruiting
    • Royal Brompton Hospital
    • Principal Investigator: S. John Wort
  • London, United Kingdom
    • Recruiting
    • Imperial Hospital
    • Principal Investigator: Martin Wilkins
  • Newcastle, United Kingdom
    • Recruiting
    • Freeman Hospital
    • Principal Investigator: James Lordan
  • Sheffield, United Kingdom
    • Recruiting
    • Sheffield Hospital
    • Principal Investigator: David Kiely

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with idiopathic, anorexigen-induced, heritable PAH or PVOD. Relative who has a family member diagnosed with idiopathic, anorexigen-induced, heritable PAH or PVOD/PCH

Description

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

Exclusion Criteria-Relative

The participant may not enter the study if ANY of the following apply:

• Patient is unable to give informed consent.

Inclusion criteria-Controls

• Participant is willing and able to give informed consent for participation in the study.
• Self-reported to be healthy
• Age range up to 75 years

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients; Patients diagnosed with idiopathic, anorexigen-induced, heritable PAH and PVOD/PCH
Relatives and controls; Relative has a family member diagnosed with idiopathic, anorexigen-induced, heritable PAH and PVOD/PCH Self declared healthy individuals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To recruit a national cohort (1000 subjects) of heritable, idiopathic PAH and PVOD/PCH cases.	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.	8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	8 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
longitudinal clinical evaluation and sampling of HPAH family members	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.	8 years
Elucidation of the underlying genetic architecture of idiopathic and heritable PAH	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	8 years

Collaborators and Investigators

• Sponsor: University of Cambridge
• Collaborators: Medical Research Council; British Heart Foundation
• Investigators: Principal Investigator: Nicholas Morrell, University of Cambridge

Publications and helpful links

Helpful Links

• Study website
• Pulmonary Hypertension patient website

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: July 8, 2013
• First Submitted That Met QC Criteria: July 18, 2013
• First Posted (Estimate): July 24, 2013

Study Record Updates

• Last Update Posted (Actual): May 20, 2022
• Last Update Submitted That Met QC Criteria: May 19, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: idiopathic; heritable; anorexigen; PCH/PVOD
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: A092860

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Consent for sharing of non identifiable study data for regulatory authorities, third parties including commercial companies outside the UK and NHS trusts where it is relevant to taking part in this research.