Clinical and Immunogenetic Characterization of Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR)

Giant Cell Arteritis Clinical Trial

Official title:

UK GCA Consortium: Clinical and Immunogenetic Characterization of Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04102930
• Other study ID #: MM05/7037
• Status: Recruiting
• Start date: June 10, 2005
• Est. completion date: February 1, 2025

Study information

• Verified date: November 2023
• Source: University of Leeds
• Contact: Louise Sorensen
• Phone: 0113 343 7764
• Email: MRCTarget[@]leeds.ac.uk
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 4000
• Est. completion date: February 1, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arteritis
• Giant Cell Arteritis
• Polymyalgia Rheumatica

Locations

Country	Name	City	State
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	Queen Elizabeth The Queen Mother Hospital	Canterbury	Kent
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	Gateshead Queen Elizabeth Hospital, Gateshead Health NHS Foundation Trust	Gateshead
United Kingdom	Inverclyde Royal Hospital, NHS Greater Glasgow and Clyde	Glasgow
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	Whiston Hospital	Prescot	Merseyside
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

Sponsors (2)

Lead Sponsor	Collaborator
University of Leeds	University of Oxford

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary outcome for genetic susceptibility studies:	Diagnosis of GCA (or PMR), confirmed by a specialist (e.g. rheumatologist, ophthalmologist) with relevant expertise.	At baseline
Secondary	Phenotype	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.	At baseline
Secondary	Life impact questionnaires	Assessment of the impact the disease and treatment has on the patients' lives as reported by the patient	At baseline
Secondary	Long term outcomes	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.	At baseline
Secondary	Diagnosis of GCA/PMR	Diagnosis in patients presenting with suspected GCA/PMR (prospective study).	Through study completion, an average of 1 year
Secondary	Exploratory analyses	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.	At baseline
Secondary	Disease activity defined as an increase in clinical and patient reported activity of disease	Participants commencing a synthetic or biological disease modifying anti-rheumatic drug with or without additional steroid therapy will have their disease activity assessed.	At baseline
Secondary	Proteomic and genomic analyses on serum, plasma and urine samples.	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.	At baseline