Clinical trial NCT04102930: Clinical and Immunogenetic Characterization of Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR)
Official title: UK GCA Consortium: Clinical and Immunogenetic Characterization of Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Giant Cell Arteritis
Polymyalgia Rheumatica
Lead sponsor: University of Leeds
Sponsor class: OTHER
Collaborators: name: University of Oxford
First posted: 2019-09-25
Enrollment: 4500
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients predominantly recruited from secondary but can be identified and/or recruited in primary care.

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

• Patient unwilling or unable to give fully informed consent.

Primary outcomes:
measure: Primary outcome for genetic susceptibility studies:
timeFrame: At baseline
Secondary outcomes:
measure: Phenotype
timeFrame: At baseline
measure: Life impact questionnaires
timeFrame: At baseline
measure: Long term outcomes
timeFrame: At baseline
measure: Diagnosis of GCA/PMR
timeFrame: Through study completion, an average of 1 year
measure: Exploratory analyses
timeFrame: At baseline
measure: Disease activity defined as an increase in clinical and patient reported activity of disease
timeFrame: At baseline
measure: Proteomic and genomic analyses on serum, plasma and urine samples.
timeFrame: At baseline
Other outcomes:
Locations:
city: Canterbury
country: United Kingdom
facility: Queen Elizabeth The Queen Mother Hospital
state: Kent
city: Prescot
country: United Kingdom
facility: Whiston Hospital
state: Merseyside
city: Abergavenny
country: United Kingdom
facility: Nevill Hall Hospital, Aneurin Bevan University Health Board
city: Aylesbury
country: United Kingdom
facility: Stoke Mandeville Hospital, Buckinghamshire Healthcare NHS Trust
city: Bangor
country: United Kingdom
facility: Betsi Cadwaladr University Health Board
city: Barnsley
country: United Kingdom
facility: Barnsley Hospital, Barnsley Hospital NHS Foundation Trust
city: Basildon
country: United Kingdom
facility: Basildon University Hospital, Basildon and Thurrock University Hospitals NHS Foundation Trust
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust
city: Bath
country: United Kingdom
facility: Royal National Hospital for Rheumatic Diseases, Royal United Hospitals Bath NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary, University Hospitals Bristol NHS Foundation Trust
city: Burton Upon Trent
country: United Kingdom
facility: Queen's Hospital, University Hospitals of Derby and Burton NHS Foundation Trust
city: Bury Saint Edmunds
country: United Kingdom
facility: West Suffolk Hospital, West Suffolk NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust
city: Chelsea
country: United Kingdom
facility: Chelsea and Westminster Hospital, Chelsea and Westminster Hospital NHS Foundation Trust
city: Chelsea
country: United Kingdom
facility: West Middlesex University Hospital, Chelsea and Westminster Hospital NHS Foundation Trust
city: Chertsey
country: United Kingdom
facility: Ashford and St Peter's Hospitals, Ashford & St Peter's Hospitals NHS Foundation Trust
city: Chester
country: United Kingdom
facility: Countess of Chester Hospital, Countess of Chester NHS Foundation Trust
city: Christchurch
country: United Kingdom
facility: Christchurch Hospital, University Hospitals Dorset NHS Foundation Trust
city: Croydon
country: United Kingdom
facility: Croydon University Hospital, Croydon Health Service NHS Trust
city: Darlington
country: United Kingdom
facility: Darlington Memorial Hospital, County Durham and Darlington NHS Foundation Trust
city: Derby
country: United Kingdom
facility: Royal Derby Hospital, University Hospitals of Derby and Burton NHS Foundation Trust
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary, Doncaster and Bassetlaw Hospitals NHS Foundation Trust
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School, NHS Tayside
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital, Royal Devon and Exeter NHS Foundation Trust
city: Frimley
country: United Kingdom
facility: Frimley Park Hospital, Frimley Park Hospital NHS Foundation Trust
city: Gateshead
country: United Kingdom
facility: Gateshead Queen Elizabeth Hospital, Gateshead Health NHS Foundation Trust
city: Glasgow
country: United Kingdom
facility: Inverclyde Royal Hospital, NHS Greater Glasgow and Clyde
city: Glasgow
country: United Kingdom
facility: Royal Alexandra Hospital, NHS Greater Glasgow and Clyde
city: Glasgow
country: United Kingdom
facility: Vale of Leven Hospital, NHS Greater Glasgow and Clyde
city: Great Yarmouth
country: United Kingdom
facility: James Paget Hospital, James Paget University Hospitals NHS Foundation Trust
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital, Royal Surrey County Hospital NHS Foundation Trust
city: Harrogate
country: United Kingdom
facility: Harrogate and District Hospital, Harrogate and District NHS Foundation Trust
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary, Hull and East Yorkshire NHS Trust
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital, East Suffolk and North Essex NHS Foundation Trust
city: Keighley
country: United Kingdom
facility: Airedale General Hospital, Airedale NHS Foundation Trust
city: Kendal
country: United Kingdom
facility: Westmorland General Hospital, University Hospitals of Morecambe Bay NHS Foundation Trust
city: Kings Lynn
country: United Kingdom
facility: The Queen Elizabeth Hospital, The Queen Elizabeth Hospital Kings Lynn NHS Foundation Trust
city: Lancaster
country: United Kingdom
facility: Royal Lancaster Infirmary, University Hospitals of Morecambe NHS Foundation Trust
city: Leeds
country: United Kingdom
facility: Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Foundation Trust
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital, Aintree University Hospitals NHS Trust
city: Llantrisant
country: United Kingdom
facility: Royal Glamorgan Hospital, Cwm Taf University Health Board
city: London
country: United Kingdom
facility: Hammersmith Hospital, Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: King's College Hospital, King's College Hospital NHS Foundation Trust, London
city: London
country: United Kingdom
facility: Royal Free Hospital, Royal Free NHS Foundation Trust
city: London
country: United Kingdom
facility: St George's Hospital, St George's University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospital, University College London NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary, Manchester University NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: Freeman Hospital, The Newcastle-upon-Tyne Hospitals NHS Foundation Trust
city: North Shields
country: United Kingdom
facility: North Tyneside General Hospital, Northumbria Healthcare NHS Foundation Trust
city: Northampton
country: United Kingdom
facility: Northampton General Hospital, Northampton General Hospital NHS Trust
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre, Nottingham University Hospitals NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Trust
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital, North West Anglia NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital, University Hospital Plymouth NHS Trust
city: Poole
country: United Kingdom
facility: Poole Hospital, University Hospitals Dorset NHS Foundation Trust
city: Preston
country: United Kingdom
facility: Minerva Health Centre, Lancashire and South Cumbria NHS Foundation Trust
city: Preston
country: United Kingdom
facility: Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust
city: Salford
country: United Kingdom
facility: Salford Royal Hospital, Salford Royal NHS Foundation Trust
city: Scarborough
country: United Kingdom
facility: Scarborough General Hospital, York and Scarborough Teaching Hospitals NHS Foundation Trust
city: Southend-on-Sea
country: United Kingdom
facility: Southend University Hospital, Southend University Hospital NHS Foundation Trust
city: Stevenage
country: United Kingdom
facility: Lister Hospital, East and North Hertfordshire NHS Trust
city: Stoke-on-Trent
country: United Kingdom
facility: Haywood Hospital, Midlands Partnership NHS Foundation Trust
city: Swindon
country: United Kingdom
facility: Great Western Hospital, The Great Western Hospitals NHS Foundation Trust
city: Torquay
country: United Kingdom
facility: Torbay Hospital, Torbay and South Devon NHS Foundation Trust
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital, Royal Cornwall Hospitals NHS Trust
city: Wakefield
country: United Kingdom
facility: Pinderfields Hospital, Mid Yorkshire Hospitals NHS Trust
city: Warrington
country: United Kingdom
facility: Warrington Hospital, Warrington and Halton Hospitals NHS Foundation Trust
city: Warwick
country: United Kingdom
facility: Warwick Hospital, South Warwickshire NHS Foundation Trust
city: Winchester
country: United Kingdom
facility: Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation Trust
city: Wirral
country: United Kingdom
facility: Arrowe Park Hospital, Wirral University Hospital NHS Foundation Trust
city: Wishaw
country: United Kingdom
facility: University Hospital Wishaw, NHS Lanarkshire
city: York
country: United Kingdom
facility: York Hospital, York and Scarborough Teaching Hospitals NHS Foundation Trust
Study officials:
affiliation: University of Leeds
name: Ann Morgan
role: PRINCIPAL_INVESTIGATOR
References: