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Trial record 3 of 130 for:    GCA

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

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ClinicalTrials.gov Identifier: NCT04102930
Recruitment Status : Recruiting
First Posted : September 25, 2019
Last Update Posted : September 25, 2019
Sponsor:
Collaborator:
University of Oxford
Information provided by (Responsible Party):
Ann Morgan, 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.

Condition or disease
Giant Cell Arteritis Polymyalgia Rheumatica

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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 4000 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Target Follow-Up Duration: 18 Months
Official Title: UK GCA Consortium: Clinical and Immunogenetic Characterization of Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR)
Actual Study Start Date : June 10, 2005
Estimated Primary Completion Date : January 31, 2025
Estimated Study Completion Date : February 1, 2025

Resource links provided by the National Library of Medicine


Group/Cohort
Retrospective
A patient who has a diagnosis of GCA or PMR
Prospective
Patient with suspected GCA and PMR



Primary Outcome Measures :
  1. Primary outcome for genetic susceptibility studies: [ Time Frame: At baseline ]
    Diagnosis of GCA (or PMR), confirmed by a specialist (e.g. rheumatologist, ophthalmologist) with relevant expertise.


Secondary Outcome Measures :
  1. Phenotype [ Time Frame: 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.

  2. Life impact questionnaires [ Time Frame: At baseline ]
    Assessment of the impact the disease and treatment has on the patients' lives as reported by the patient

  3. Long term outcomes [ Time Frame: 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.

  4. Diagnosis of GCA/PMR [ Time Frame: Through study completion, an average of 1 year ]
    Diagnosis in patients presenting with suspected GCA/PMR (prospective study).

  5. Exploratory analyses [ Time Frame: 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.

  6. Disease activity defined as an increase in clinical and patient reported activity of disease [ Time Frame: 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.

  7. Proteomic and genomic analyses on serum, plasma and urine samples. [ Time Frame: 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.


Biospecimen Retention:   Samples With DNA
Serum, plasma, cellular and subcellular fractions of blood, urine or arterial tissue, DNA, RNA, proteins and metabolites


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients predominantly recruited from secondary but can be identified and/or recruited in primary care.
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.


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): NCT04102930


Contacts
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Contact: Louise Sorensen 0113 343 7764 MRCTarget@leeds.ac.uk
Contact: Rachael Kearns 0113 343 7764 MRCTarget@leeds.ac.uk

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Sponsors and Collaborators
University of Leeds
University of Oxford
Investigators
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Principal Investigator: Ann Morgan University of Leeds

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Responsible Party: Ann Morgan, Professor of Molecular Rheumatology and Honorary Consultant Rheumatologist, University of Leeds
ClinicalTrials.gov Identifier: NCT04102930     History of Changes
Other Study ID Numbers: MM05/7037
First Posted: September 25, 2019    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Polymyalgia Rheumatica
Giant Cell Arteritis
Arteritis
Vasculitis
Vascular Diseases
Cardiovascular Diseases
Vasculitis, Central Nervous System
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Skin Diseases, Vascular
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases