Aetiology of TemporaL Arteritis Study

Temporal Arteritis Clinical Trial

— ATLAS  

Official title:

Understanding the Aetiology and Pathogenesis of Giant Cell Arteritis

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02584517
• Other study ID #: ATLAS001
• Status: Withdrawn
• Start date: January 2016
• Est. completion date: January 2021

Study information

• Verified date: October 2015
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2021
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Arteritis
• Giant Cell Arteritis
• Temporal Arteritis

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	University of Leeds

References & Publications (5)

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

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 marro — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	CD70 in GCA	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
Secondary	IL-7 and sIL-7R in GCA	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
Secondary	Vascular Endothelial Growth Factor (VEGF) levels over time	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
Secondary	Pentraxin 3 levels over time	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
Secondary	Archiving of tissue for future studies	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+