NCT06460142

Assessing Biomarker in Giant Cell Arteritis and Polymyalgia Rheumatic

Multimodal Assessment of Biomarkers for Diagnosing Giant Cell Arteritis and Polymyalgia Rheumatica: A Comprehensive Analysis of Clinical, Laboratory, and Imaging Profiles

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 100 (estimated)
• Sponsor: University of Bonn · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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.

Detailed description

GCA is an immune-mediated vasculitis that affects medium and large-sized vessels, leading to vascular changes and occlusion due to severe vascular inflammation, neoangiogenesis, and remodeling. GCA has the potential to impact almost any organ. Despite advancements in understanding the pathophysiology and clinical manifestations of GCA, many aspects of the disease remain unexplored. The GCAIO study aims to fill these gaps using an integrative research approach to enhance the diagnosis, understanding, and management of GCA. The GCAIO study cohort includes patients at their first diagnosis, throughout the disease, and during recurrent activity, facilitating a thorough longitudinal analysis of GCA. The research focuses on the complex immunological processes of the disease. Techniques such as flow cytometry (FACS), enzyme-linked immunosorbent assays (ELISA), and 3'-mRNA transcriptome analysis are employed to identify biomarkers that can assess GCA activity, track disease progression, and predict therapeutic responses, particularly for those unresponsive to interleukin (IL)-6 receptor (R) inhibitors. Additionally, the project is pioneering personalized treatment protocols tailored to individual immune profiles by developing a cell-based ex-vivo assay designed to forecast how patients will respond to different disease-modifying anti-rheumatic drugs (DMARDs). Alongside the immunological research, the project emphasizes improving diagnostic and monitoring techniques through imaging technologies. Recent advancements have demonstrated that optimized diagnostics significantly enhance treatment outcomes for GCA patients. The planned prospective multimodal imaging aims to investigate potential neuro-ophthalmological, cardiac, and aortic manifestations during the course of GCA, enabling a detailed assessment of the involvement of various structures. Established imaging methods such as magnetic resonance imaging (MRI), optical coherence tomography angiography (OCTA), and vascular ultrasound are being extended into new areas to evaluate their diagnostic and prognostic merits. Furthermore, the investigators are exploring innovative diagnostic tools like transorbital ultrasound (TOS) and contrast-enhanced ultrasound (CEUS) for their potential as predictive biomarkers, facilitating earlier diagnosis and more precise disease monitoring. By correlating imaging findings with immunological data, our goal is to alter the way GCA is detected and monitored. The inclusion of patients with PMR enhances our understanding of its pathophysiology, clinical manifestations, and its connection to often-associated GCA. The investigators are dedicated to developing new diagnostic criteria and exploring alternative therapeutic approaches for PMR maintenance therapy. By identifying alternative clinical, laboratory, or instrumental diagnostic methods to predict PMR, the investigators aim to set new diagnostic standards and deepen our understanding of its pathophysiology and immunological processes. In summary, the goal of the GCAIO study is to make substantial contributions to the fields of GCA and PMR by developing innovative diagnostic and therapeutic strategies that improve treatment and quality of life for affected patients. The identification of specific biomarkers and the establishment of new diagnostic standards could lead to more precise diagnoses and optimized management of therapy, thereby enhancing patient care and reducing the risk of complications and therapy failures.

Conditions

• Giant Cell Arteritis
• Polymyalgia Rheumatica

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	Vascular ultrasound	Vascular ultrasound will be employed to examine the temporal and axillary arteries in GCA patients, searching for signs indicative of active inflammation.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	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.
DIAGNOSTIC_TEST	Laboratory assessment:	Serum Chemistry (nt-proBNP, troponin T, CRP, ESR, blood count)
DIAGNOSTIC_TEST	Immunohistochemistry of Temporal Artery Biopsies	Immunohistochemistry staining of TAB to assess local expression of endothelial adhesion molecules in acute inflammation.
DIAGNOSTIC_TEST	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.

Timeline

• Start date: 2023-09-01
• Primary completion: 2026-09-30
• Completion: 2027-09-30
• First posted: 2024-06-14
• Last updated: 2025-04-10

Locations

1 site across 1 country: Germany