Assessing Biomarker in Giant Cell Arteritis and Polymyalgia Rheumatic

Summary

The GCAIO study is an innovative, multimodal research initiative designed to enhance the understanding, diagnosis, and management of giant cell arteritis (GCA) and frequently associated polymyalgia rheumatica (PMR). This longitudinal study aims to dissect the complex immunological landscape and systemic manifestations of these conditions through a combination of diagnostic imaging and detailed immunological profiling.

The study focuses on three primary objectives: (1) Identifying and analyzing cytokine profiles and immune cell phenotypes, employing techniques like flow cytometry, enzyme-linked immunosorbent assays (ELISA), and next-generation sequencing to predict disease activity and therapeutic responses. (2) Advancing diagnostic and monitoring capabilities through the application of novel and established imaging technologies, including MRI, optical coherence tomography angiography (OCTA), and ultrasound. These modalities aim to improve the detection of neuro-ophthalmological, cardiac, and aortic complications in GCA, potentially offering more precise monitoring and earlier diagnosis. (3) Enhancing the understanding of PMR within the context of GCA by exploring specific biomarkers and advanced imaging to refine diagnostic accuracy and treatment strategies, thus improving patient outcomes.

Conditions

• Giant Cell Arteritis
• Polymyalgia Rheumatica

Interventions

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Aortic/ cardiac magnetic resonance imaging

MRI scans will be performed to detect systemic vascular involvement in GCA patients, aiming to provide detailed images of affected tissues.

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Vascular ultrasound

Vascular ultrasound will be employed to examine the temporal and axillary arteries in GCA patients, searching for signs indicative of active inflammation.

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Transorbital Ultrasound

Transorbital ultrasound will be employed to assess the ophthalmic artery and its branches in GCA patients to detect intracranial inflammatory processes that could lead to severe neuro-ophthalmological complications.

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Contrast-Enhanced Ultrasound

Contrast-Enhanced Ultrasound (CEUS) is utilized to evaluate aortic involvement in GCA patients as an alternative, bed-side, realtime, radiation-free diagnostic tool.

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Optical coherence tomography angiography

OCTA will be used to assess vascular changes in the retina of GCA patients, providing detailed imaging that can help detect early signs of ocular involvement and identify risk factors of anterior ischemic optic neuropathy.

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Fluorescein angiography

Fluorescein angiography will be performed to evaluate blood circulation and highlight any blockages in the blood vessels of the retina in patients with GCA to detect vascular abnormalities that may lead to severe vision complications.

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Fundus autofluorescence

This imaging technique will be used to observe the health of the retina and detect any changes in GCA patients that could suggest disease activity, particularly useful for assessing the integrity of the retinal pigment epithelium.

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Color Fundus Photography

Color fundus photography will be used to document the appearance of the optic disc and retinal vasculature in GCA patients, aiding in the long-term monitoring of ocular changes and the effects of therapeutic interventions.

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Cell-based ex-vivo assay with high-content analysis

This assay predicts individual patient responses to different DMARDs by analyzing patient-derived PBMCs for specific immune responses to therapeutic agents.

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3'mRNA sequencing

3'mRNA sequencing analyzes gene expression profiles related to the immune response in PMR/GCA patients, aiding in understanding the genetic underpinnings of inflammation and vascular remodeling.

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Enzyme-linked immunosorbent assay

Used to measure cytokine levels in the serum and plasma of PMR/GCA patients, ELISA aids in profiling inflammatory markers that are indicative of disease activity and response to treatment.

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Flow cytometry

Employed to analyze immune cell phenotypes in patients with PMR and/or GCA, this test helps identify various immune cell subsets and their activation states, which are critical for understanding disease mechanisms and guiding therapy.

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Laboratory assessment:

Serum Chemistry (nt-proBNP, troponin T, CRP, ESR, blood count)

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Immunohistochemistry of Temporal Artery Biopsies

Immunohistochemistry staining of TAB to assess local expression of endothelial adhesion molecules in acute inflammation.

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Functional assessment questionnaires

The following questionnaires will be applied: FACIT-Fatigue, SF-36, BAS, Birmingham Vasculitis Activity Score, Montreal Cognitive Assessment, Mini-Mental Status Examination. These questionnaires collectively provide a comprehensive evaluation of the functional status, quality of life, and mental health of patients with GCA and PMR.

Sponsors & Collaborators

• University of Bonn

  lead OTHER

Principal Investigators

• Valentin S. Schäfer, Univ. Prof. · Department of Rheumatology and Clinical Immunology, University Hospital Bonn

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-09-01

Primary Completion

2026-09-30

Completion

2027-09-30

Countries

• Germany

Study Locations