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

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ClinicalTrials.gov Identifier: NCT01907295
Recruitment Status : Recruiting
First Posted : July 24, 2013
Last Update Posted : May 20, 2022
Sponsor:
Collaborators:
British Heart Foundation
Medical Research Council
Information provided by (Responsible Party):
Nick Morrell, University of Cambridge

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)


Condition or disease
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

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 3600 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 3 Years
Official Title: National Cohort Study of Idiopathic and Heritable Pulmonary Arterial Hypertension
Actual Study Start Date : February 2014
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022


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



Primary Outcome Measures :
  1. To recruit a national cohort (1000 subjects) of heritable, idiopathic PAH and PVOD/PCH cases. [ Time Frame: 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 Outcome Measures :
  1. 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. [ Time Frame: 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 Outcome Measures:
  1. longitudinal clinical evaluation and sampling of HPAH family members [ Time Frame: 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.

  2. Elucidation of the underlying genetic architecture of idiopathic and heritable PAH [ Time Frame: 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


Biospecimen Retention:   Samples With DNA
All subjects will have a sample of blood taken for next generation genetic sequencing (up to their entire genome). Samples will be sequenced to identify novel genetic mutations associated with PAH. This blood sample will be taken once during the study


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01907295


Contacts
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Contact: Nicholas Morrell 01223 331666 nwm23@cam.ac.uk
Contact: Carmen Treacy 1223 763094 cohortcoordination@medschl.cam.ac.uk

Locations
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United Kingdom
Royal United Hospitals Bath Recruiting
Bath, United Kingdom, BA1 3NG
Contact: Robert MacKenenzie Ross, PI         
Royal Papworth Hospital NHS Trust Recruiting
Cambridge, United Kingdom
Principal Investigator: Joanna Pepke-Zaba         
Golden Jubilee National Hospital Recruiting
Glasgow, United Kingdom
Principal Investigator: Colin Church         
Imperial Hospital Recruiting
London, United Kingdom
Principal Investigator: Martin Wilkins         
Royal Brompton Hospital Recruiting
London, United Kingdom
Principal Investigator: S. John Wort         
Royal Free Hospital Recruiting
London, United Kingdom
Principal Investigator: Gerry Goglan         
Freeman Hospital Recruiting
Newcastle, United Kingdom
Principal Investigator: James Lordan         
Sheffield Hospital Recruiting
Sheffield, United Kingdom
Principal Investigator: David Kiely         
Sponsors and Collaborators
University of Cambridge
British Heart Foundation
Medical Research Council
Investigators
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Principal Investigator: Nicholas Morrell University of Cambridge
Additional Information:
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Responsible Party: Nick Morrell, BHF Professor of Cardiopulmonary Medicine, University of Cambridge
ClinicalTrials.gov Identifier: NCT01907295    
Other Study ID Numbers: A092860
First Posted: July 24, 2013    Key Record Dates
Last Update Posted: May 20, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.
Keywords provided by Nick Morrell, University of Cambridge:
idiopathic
heritable
anorexigen
PCH/PVOD
Additional relevant MeSH terms:
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Pulmonary Arterial Hypertension
Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases