- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02584517
Aetiology of TemporaL Arteritis Study (ATLAS)
Understanding the Aetiology and Pathogenesis of Giant Cell Arteritis
Study Overview
Status
Conditions
Detailed Description
Objectives and Study Plan:
Study Purpose:
The purpose of the study is to investigate the underlying immunological processes in GCA and to study the pattern of expression of immune response over time to give us information about how best to monitor GCA.
End Point:
The end point will be the final visit of the final patient.
Milestones:
The project is in 3 phases. In phase 1 (0-2 years) patients will be recruited to fulfil the specified primary and secondary objectives. In phase 2 (0-4 years), these patients will be followed up for a total of 2 years each, or until they are discharged from clinic. In phase 3 (1-5 years), further studies will be defined and tissue and data collected under amended ethics.
Study Type
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- 18 years of age or over
- A clinical suspicion of a new diagnosis of GCA e.g. patients with a new onset of headache, scalp tenderness, with or without elevated CRP or ESR, jaw or tongue claudication with or without visual loss
- Participants must be willing to give informed written consent or willing to give permission for a nominated friend or relative to provide written informed assent if they are unable to do so because of physical disabilities e.g. sudden onset of blindness/vision loss which can be caused by GCA (this will be made clear in the ethics approval application)
Exclusion Criteria:
- Previous diagnosis of GCA
- Long term (>1 month) high dose (>20mg per day at any time) steroids for conditions other than PMR, within three months prior to study entry
- Inability to give informed consent (either written consent or verbal assent from a relative or carer)
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
---|
GCA
Patients referred with suspected GCA, whose final diagnosis is GCA
|
Not GCA
Patients referred with suspected GCA, whose final diagnosis is another disorder
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phenotyping of innate lymphoid cells (ILC) in the arterial wall and blood of patients with GCA
Time Frame: 24 months
|
Arterial biopsy tissue and peripheral blood will be collected from patients with suspected GCA.
A proportion of these will be diagnosed with GCA and will be the "test" subjects, and a proportion will be diagnosed with other conditions that are not GCA and will be the "controls".
We will use immunohistochemistry and immunofluorescence microscopy to locate and phenotype ILC in arterial biopsies.
We will use semi-quantitative methods (ie cells per random high powered field) to compare prevalence of ILC in tests and controls.
We will also isolate peripheral blood mononuclear cells (PBMCs) from fresh whole blood, and stain the cells to use flow cytometry to quantify and phenotype the ILC.
Tests and Controls will be compared using Mann-Whitney statistical testing.
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
CD70 in GCA
Time Frame: 12 months
|
CD70 is a costimulatory molecule which is present for a short time on the surface of activated T cells.
CD70 has been studied in other autoimmune conditions such as systemic lupus, where it is involved in generating the self-reactive factors responsible for the disease.
It is therefore suggested that it might be involved in the development of another autoimmune vasculitis, GCA.
We will quantify and phenotype CD70+ve cells in peripheral blood and biopsies of patients with GCA and in controls.
We will also measure the levels of the soluble form of its receptor, CD27, in patients and controls.
|
12 months
|
IL-7 and sIL-7R in GCA
Time Frame: 36 months
|
IL-7 is a key cytokine for development of all lymphoid cells, including ILC.
Levels of sIL-7R have been linked to active renal disease in systemic lupus, and sIL-7R is suggested as a biomarker of lupus.
We will collect serum at several time points from patients with GCA and controls (see primary outcome measures).
The level of IL-7 and sIL-7R will be quanitified by Enzyme-linked Immunosorbent Assay (ELISA) and the results plotted as time series.
We will analyse the trends of these series to see how useful IL-7 and sIL-7R may be in monitoring GCA.
|
36 months
|
Vascular Endothelial Growth Factor (VEGF) levels over time
Time Frame: 36 months
|
VEGF is a putative biomarker of GCA.
We will collect serum at several time points from patients with GCA and controls (see primary outcome measures).
The level of VEGF will be quanitified by Enzyme-linked Immunosorbent Assay (ELISA) and the results plotted as time series.
We will analyse the trends of these series to see how useful VEGF may be in monitoring GCA.
|
36 months
|
Pentraxin 3 levels over time
Time Frame: 36 months
|
Pentraxin 3 is a second biomarker of interest in GCA, and we plan to analyse its expression in peripheral blood as for VEGF.
|
36 months
|
Archiving of tissue for future studies
Time Frame: 60 months+
|
The cohort of patients recruited to this study represents a valuable resource for future ethically-approved studies of the aetiology of GCA.
We believe that the majority of patients would like their donations to contribute to as much research as possible.
Therefore we will archive tissue in the form of blood fractions and temporal artery biopsy specimens, as well as linking to anonymized clinical and imaging data.
It is planned that the study ethics will be amended with novel substudies as they are designed.
|
60 months+
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Raashid A Luqmani, DM FRCP, University of Oxford
Publications and helpful links
General Publications
- Weyand CM, Goronzy JJ. Immune mechanisms in medium and large-vessel vasculitis. Nat Rev Rheumatol. 2013 Dec;9(12):731-40. doi: 10.1038/nrrheum.2013.161. Epub 2013 Nov 5.
- Artis D, Spits H. The biology of innate lymphoid cells. Nature. 2015 Jan 15;517(7534):293-301. doi: 10.1038/nature14189.
- Ciccia F, Guggino G, Rizzo A, Saieva L, Peralta S, Giardina A, Cannizzaro A, Sireci G, De Leo G, Alessandro R, Triolo G. Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis. Ann Rheum Dis. 2015 Sep;74(9):1739-47. doi: 10.1136/annrheumdis-2014-206323. Epub 2015 Apr 22.
- Kozlowska A, Hrycaj P, Lacki JK, Jagodzinski PP. Fyn and CD70 expression in CD4+ T cells from patients with systemic lupus erythematosus. J Rheumatol. 2010 Jan;37(1):53-9. doi: 10.3899/jrheum.090424. Epub 2009 Dec 1.
- Lauwerys BR, Husson SN, Maudoux AL, Badot V, Houssiau FA. sIL7R concentrations in the serum reflect disease activity in the lupus kidney. Lupus Sci Med. 2014 Jul 17;1(1):e000036. doi: 10.1136/lupus-2014-000036. eCollection 2014.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Skin Diseases
- Immune System Diseases
- Autoimmune Diseases of the Nervous System
- Autoimmune Diseases
- Vasculitis
- Skin Diseases, Vascular
- Vasculitis, Central Nervous System
- Giant Cell Arteritis
- Arteritis
Other Study ID Numbers
- ATLAS001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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