Aetiology of TemporaL Arteritis Study

NCT02584517 | Withdrawn

• 1 other identifier: ATLAS001
• Study Type: observational
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Temporal Arteritis

Keywords

Vasculitis; Autoimmune disease; Connective tissue disease; Polymyalgia rheumatica; Musculoskeletal Diseases; Immune disorder; Rheumatic disease

Outcome Measures

Primary Outcomes (1)

• Phenotyping of innate lymphoid cells (ILC) in the arterial wall and blood of patients with GCA

  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 Outcomes (5)

• CD70 in GCA

  12 months

• IL-7 and sIL-7R in GCA

  36 months

• Vascular Endothelial Growth Factor (VEGF) levels over time

  36 months

• Pentraxin 3 levels over time

  36 months

• Archiving of tissue for future studies

  60 months+

Study Arms (2)

GCA

Patients referred with suspected GCA, whose final diagnosis is GCA

Not GCA

Patients referred with suspected GCA, whose final diagnosis is another disorder

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Oxford: lead
• University of Leeds: collaborator

Related Publications (5)

• 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.

  PMID: 24189842 RESULT

• Artis D, Spits H. The biology of innate lymphoid cells. Nature. 2015 Jan 15;517(7534):293-301. doi: 10.1038/nature14189.

  PMID: 25592534 RESULT

• 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.

  PMID: 25902790 RESULT

• 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.

  PMID: 19955046 RESULT

• 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.

  PMID: 25396066 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Serum Plasma Peripheral Blood Mononuclear Cells Whole blood

MeSH Terms

Conditions

Giant Cell Arteritis; Vasculitis; Autoimmune Diseases; Connective Tissue Diseases; Polymyalgia Rheumatica; Musculoskeletal Diseases; Immune System Diseases; Rheumatic Diseases

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Muscular Diseases

Study Officials

• Raashid A Luqmani, DM FRCP

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: October 22, 2015
• Study Start: January 1, 2016
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2021
• Last Updated: August 15, 2022

Record last verified: 2015-10