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Aetiology of TemporaL Arteritis Study (ATLAS)

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ClinicalTrials.gov Identifier: NCT02584517
Recruitment Status : Not yet recruiting
First Posted : October 22, 2015
Last Update Posted : October 22, 2015
Sponsor:
Collaborator:
University of Leeds
Information provided by (Responsible Party):
University of Oxford

Brief Summary:
Giant Cell Arteritis (GCA) is the most common vasculitis and has significant morbidity in terms of blindness, stroke, and tissue necrosis. It requires protracted treatment with high-dose steroids, and despite this there is a risk of flare during the treatment. Little is known about the initial triggers for the inflammatory process, and there are no good markers of response or relapse. We will study patients referred with suspected GCA to identify important components of the immune response in GCA, and follow them over time to collect evidence of how best to monitor their condition.

Condition or disease
Temporal Arteritis

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.


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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Understanding the Aetiology and Pathogenesis of Giant Cell Arteritis
Study Start Date : January 2016
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.


Biospecimen Retention:   Samples With DNA
Serum Plasma Peripheral Blood Mononuclear Cells Whole blood


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The proposed study will recruit a cohort of eligible patients (predominantly from primary care referrals) suspected by their referring doctor to have new onset of GCA.
Criteria

Inclusion Criteria:

  1. 18 years of age or over
  2. 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
  3. 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:

  1. Previous diagnosis of GCA
  2. 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
  3. Inability to give informed consent (either written consent or verbal assent from a relative or carer)

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): NCT02584517


Contacts
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Contact: Raashid A Luqmani, DM FRCP 01865227971 raashid.luqmani@ndorms.ox.ac.uk
Contact: Jana Vaskova 01865227971 jana.vaskova@ndorms.ox.ac.uk

Sponsors and Collaborators
University of Oxford
University of Leeds
Investigators
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Principal Investigator: Raashid A Luqmani, DM FRCP University of Oxford

Publications of Results:
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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT02584517     History of Changes
Other Study ID Numbers: ATLAS001
First Posted: October 22, 2015    Key Record Dates
Last Update Posted: October 22, 2015
Last Verified: October 2015

Keywords provided by University of Oxford:
Vasculitis
Autoimmune disease
Connective tissue disease
Polymyalgia rheumatica
Musculoskeletal Diseases
Immune disorder
Rheumatic disease

Additional relevant MeSH terms:
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Vasculitis
Vasculitis, Central Nervous System
Arteritis
Giant Cell Arteritis
Vascular Diseases
Cardiovascular Diseases
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