Clinical and Immunogenetic Characterization of Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR)
- Conditions
- Polymyalgia RheumaticaGiant Cell Arteritis
- Registration Number
- NCT04102930
- Lead Sponsor
- University of Leeds
- Brief Summary
A multi-centre observational study recruiting prospective and retrospective cohorts of patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). The primary aim is to find genetic determinants of GCA and PMR susceptibility, in order to yield novel insights into disease pathogenesis. A subset of the retrospective cohort is also enrolled in a post-marketing surveillance registry of patients eligible for, or receiving tocilizumab, to treat their relapsing or refractory GCA.
- Detailed Description
Giant cell arteritis (GCA), also known as temporal arteritis, is the most common form of primary systemic vasculitis, with up to 75,000 cases a year identified in the EU and US. It occurs almost exclusively in people over the age of 50 years and is considered to be a medical emergency. If not treated with high-dose glucocorticoids immediately, the thickening of the inflamed blood vessel wall can cause irreversible visual loss or stroke. GCA can lead to significant morbidity across a variety of systems, due to both the disease, and complications of treatment. Diagnosis may be confirmed with a temporal artery biopsy, imaging (e.g. USS/CT/MRA/PET-CR) or based on clinical signs (e.g. erythrocyte sedimentation rate) and symptoms (e.g. a new headache, jaw claudication, visual disturbances, temporal artery abnormality such as tenderness or decreased pulsation) .
Polymyalgia rheumatica (PMR) is characterised by inflammatory limb-girdle pain with early morning stiffness, and a systemic inflammatory response demonstrated by elevated inflammatory markers.
The UK GCA Consortium is a multi-centre observational study, the main arms of which recruit prospective (participants with suspected GCA) and retrospective cohorts (participants with confirmed GCA diagnosis). Analysis of data collected on these cohorts will help achieve the primary aim of finding genetic determinants of GCA and PMR susceptibility, in order to yield novel insights into disease pathogenesis. Secondary aims, and their associated analyses, are as follows:
* Phenotype: characterising GCA and PMR subtypes, based on clinical features; imaging; cells; subcellular fractions and molecules in the circulation and/or arterial tissue; genetic/epigenetic/transcriptomic/proteomic or metabolomics factors, including next generation sequencing (whole exome sequencing) of selected cases.
* Life impact: determining what aspects of the disease and treatments affect patients' quality of life, as assessed by patient-reported outcomes.
* Long-term outcomes: characterising prognosis of GCA and PMR - both effects of the disease and its treatment - by longitudinal follow-up through electronic linkage to health records.
* Exploratory analyses: exploring the potential role of environmental factors and co-morbidities on phenotype and outcomes.
* Diagnosis, prognosis: improving diagnosis of GCA and PMR, and identifying factors that predict diagnosis, such as diagnostic clinical features, and prognostic and diagnostic biomarkers.
* Disease activity: monitoring participants who commence a synthetic or biological disease-modifying anti-rheumatic drug (s/bDMARD). Finding a biomarker for GCA and PMR disease activity, which might be clinically useful in helping to optimise steroid and s/bDMARD treatments for individual patients.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 4500
- Willing to self-identify an ethnic group, such as Caucasian, Asian, Afro-Caribbean.
- Have a firm clinical diagnosis of GCA or PMR, or (for patients identified prospectively) GCA or PMR should be more likely than any alternative explanation for the patient's symptoms.
- Able and willing to give informed consent. Patients will be 50 years of age or over, unless both biopsy-proven and a clinically classical case of GCA.
• Patient unwilling or unable to give fully informed consent.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary outcome for genetic susceptibility studies: At baseline Diagnosis of GCA (or PMR), confirmed by a specialist (e.g. rheumatologist, ophthalmologist) with relevant expertise.
- Secondary Outcome Measures
Name Time Method Phenotype At baseline Clinical phenotype or subtype of GCA/PMR based on disease features and imaging undertaken as part of routine clinical practice, and on research tests, such as imaging performed for research purposes, cells, subcellular fractions and molecules in the circulation and/or arterial tissue and genetic/ epigenetic/ transcriptomic/ proteomic or metabolomic factors, including next generation sequencing (whole exome sequencing) of selected cases.
Life impact questionnaires At baseline Assessment of the impact the disease and treatment has on the patients' lives as reported by the patient
Disease activity defined as an increase in clinical and patient reported activity of disease At baseline Participants commencing a synthetic or biological disease modifying anti-rheumatic drug with or without additional steroid therapy will have their disease activity assessed.
Long term outcomes At baseline Longitudinal follow-up of patients (as far as is possible from medical and electronic records and without requiring additional study visits) to define prognosis/disease outcomes, such as ischaemic manifestations, aneurysm formation, duration of steroid therapy, disease flares, complications related to steroid therapy.
Exploratory analyses At baseline To investigate role of genetics, environmental factors (e.g. diet and sunlight) and co-morbidities (e.g. periodontal disease) on disease phenotype and outcome as assessed by the patient-administered questionnaires.
Proteomic and genomic analyses on serum, plasma and urine samples. At baseline A variety of 'omic technologies will be applied to cell populations isolated from the blood and/or routine diagnostic arterial biopsies, including, but not limited to, RNASeq and a variety of proteomic approaches.
Diagnosis of GCA/PMR Through study completion, an average of 1 year Diagnosis in patients presenting with suspected GCA/PMR (prospective study).
Trial Locations
- Locations (76)
Queen Elizabeth The Queen Mother Hospital
🇬🇧Canterbury, Kent, United Kingdom
Whiston Hospital
🇬🇧Prescot, Merseyside, United Kingdom
Nevill Hall Hospital, Aneurin Bevan University Health Board
🇬🇧Abergavenny, United Kingdom
Stoke Mandeville Hospital, Buckinghamshire Healthcare NHS Trust
🇬🇧Aylesbury, United Kingdom
Betsi Cadwaladr University Health Board
🇬🇧Bangor, United Kingdom
Barnsley Hospital, Barnsley Hospital NHS Foundation Trust
🇬🇧Barnsley, United Kingdom
Basildon University Hospital, Basildon and Thurrock University Hospitals NHS Foundation Trust
🇬🇧Basildon, United Kingdom
Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust
🇬🇧Basingstoke, United Kingdom
Royal National Hospital for Rheumatic Diseases, Royal United Hospitals Bath NHS Foundation Trust
🇬🇧Bath, United Kingdom
Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Bristol Royal Infirmary, University Hospitals Bristol NHS Foundation Trust
🇬🇧Bristol, United Kingdom
Queen's Hospital, University Hospitals of Derby and Burton NHS Foundation Trust
🇬🇧Burton Upon Trent, United Kingdom
West Suffolk Hospital, West Suffolk NHS Foundation Trust
🇬🇧Bury Saint Edmunds, United Kingdom
Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Chelsea and Westminster Hospital, Chelsea and Westminster Hospital NHS Foundation Trust
🇬🇧Chelsea, United Kingdom
West Middlesex University Hospital, Chelsea and Westminster Hospital NHS Foundation Trust
🇬🇧Chelsea, United Kingdom
Ashford and St Peter's Hospitals, Ashford & St Peter's Hospitals NHS Foundation Trust
🇬🇧Chertsey, United Kingdom
Countess of Chester Hospital, Countess of Chester NHS Foundation Trust
🇬🇧Chester, United Kingdom
Christchurch Hospital, University Hospitals Dorset NHS Foundation Trust
🇬🇧Christchurch, United Kingdom
Croydon University Hospital, Croydon Health Service NHS Trust
🇬🇧Croydon, United Kingdom
Darlington Memorial Hospital, County Durham and Darlington NHS Foundation Trust
🇬🇧Darlington, United Kingdom
Royal Derby Hospital, University Hospitals of Derby and Burton NHS Foundation Trust
🇬🇧Derby, United Kingdom
Doncaster Royal Infirmary, Doncaster and Bassetlaw Hospitals NHS Foundation Trust
🇬🇧Doncaster, United Kingdom
Ninewells Hospital and Medical School, NHS Tayside
🇬🇧Dundee, United Kingdom
Royal Devon and Exeter Hospital, Royal Devon and Exeter NHS Foundation Trust
🇬🇧Exeter, United Kingdom
Frimley Park Hospital, Frimley Park Hospital NHS Foundation Trust
🇬🇧Frimley, United Kingdom
Inverclyde Royal Hospital, NHS Greater Glasgow and Clyde
🇬🇧Glasgow, United Kingdom
Gateshead Queen Elizabeth Hospital, Gateshead Health NHS Foundation Trust
🇬🇧Gateshead, United Kingdom
Royal Alexandra Hospital, NHS Greater Glasgow and Clyde
🇬🇧Glasgow, United Kingdom
Vale of Leven Hospital, NHS Greater Glasgow and Clyde
🇬🇧Glasgow, United Kingdom
James Paget Hospital, James Paget University Hospitals NHS Foundation Trust
🇬🇧Great Yarmouth, United Kingdom
Royal Surrey County Hospital, Royal Surrey County Hospital NHS Foundation Trust
🇬🇧Guildford, United Kingdom
Harrogate and District Hospital, Harrogate and District NHS Foundation Trust
🇬🇧Harrogate, United Kingdom
Hull Royal Infirmary, Hull and East Yorkshire NHS Trust
🇬🇧Hull, United Kingdom
Ipswich Hospital, East Suffolk and North Essex NHS Foundation Trust
🇬🇧Ipswich, United Kingdom
Airedale General Hospital, Airedale NHS Foundation Trust
🇬🇧Keighley, United Kingdom
Westmorland General Hospital, University Hospitals of Morecambe Bay NHS Foundation Trust
🇬🇧Kendal, United Kingdom
The Queen Elizabeth Hospital, The Queen Elizabeth Hospital Kings Lynn NHS Foundation Trust
🇬🇧Kings Lynn, United Kingdom
Royal Lancaster Infirmary, University Hospitals of Morecambe NHS Foundation Trust
🇬🇧Lancaster, United Kingdom
Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Foundation Trust
🇬🇧Leeds, United Kingdom
Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust
🇬🇧Leicester, United Kingdom
Aintree University Hospital, Aintree University Hospitals NHS Trust
🇬🇧Liverpool, United Kingdom
Royal Glamorgan Hospital, Cwm Taf University Health Board
🇬🇧Llantrisant, United Kingdom
Hammersmith Hospital, Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
King's College Hospital, King's College Hospital NHS Foundation Trust, London
🇬🇧London, United Kingdom
Royal Free Hospital, Royal Free NHS Foundation Trust
🇬🇧London, United Kingdom
St George's Hospital, St George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
University College London Hospital, University College London NHS Foundation Trust
🇬🇧London, United Kingdom
Manchester Royal Infirmary, Manchester University NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Freeman Hospital, The Newcastle-upon-Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle, United Kingdom
North Tyneside General Hospital, Northumbria Healthcare NHS Foundation Trust
🇬🇧North Shields, United Kingdom
Northampton General Hospital, Northampton General Hospital NHS Trust
🇬🇧Northampton, United Kingdom
Norfolk and Norwich University Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust
🇬🇧Norwich, United Kingdom
Queens Medical Centre, Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Oxford Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Trust
🇬🇧Oxford, United Kingdom
Peterborough City Hospital, North West Anglia NHS Foundation Trust
🇬🇧Peterborough, United Kingdom
Derriford Hospital, University Hospital Plymouth NHS Trust
🇬🇧Plymouth, United Kingdom
Poole Hospital, University Hospitals Dorset NHS Foundation Trust
🇬🇧Poole, United Kingdom
Minerva Health Centre, Lancashire and South Cumbria NHS Foundation Trust
🇬🇧Preston, United Kingdom
Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust
🇬🇧Preston, United Kingdom
Salford Royal Hospital, Salford Royal NHS Foundation Trust
🇬🇧Salford, United Kingdom
Scarborough General Hospital, York and Scarborough Teaching Hospitals NHS Foundation Trust
🇬🇧Scarborough, United Kingdom
Southend University Hospital, Southend University Hospital NHS Foundation Trust
🇬🇧Southend-on-Sea, United Kingdom
Lister Hospital, East and North Hertfordshire NHS Trust
🇬🇧Stevenage, United Kingdom
Haywood Hospital, Midlands Partnership NHS Foundation Trust
🇬🇧Stoke-on-Trent, United Kingdom
Great Western Hospital, The Great Western Hospitals NHS Foundation Trust
🇬🇧Swindon, United Kingdom
Torbay Hospital, Torbay and South Devon NHS Foundation Trust
🇬🇧Torquay, United Kingdom
Royal Cornwall Hospital, Royal Cornwall Hospitals NHS Trust
🇬🇧Truro, United Kingdom
Pinderfields Hospital, Mid Yorkshire Hospitals NHS Trust
🇬🇧Wakefield, United Kingdom
Warrington Hospital, Warrington and Halton Hospitals NHS Foundation Trust
🇬🇧Warrington, United Kingdom
Warwick Hospital, South Warwickshire NHS Foundation Trust
🇬🇧Warwick, United Kingdom
Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation Trust
🇬🇧Winchester, United Kingdom
Arrowe Park Hospital, Wirral University Hospital NHS Foundation Trust
🇬🇧Wirral, United Kingdom
University Hospital Wishaw, NHS Lanarkshire
🇬🇧Wishaw, United Kingdom
York Hospital, York and Scarborough Teaching Hospitals NHS Foundation Trust
🇬🇧York, United Kingdom