Assessing Biomarker in Giant Cell Arteritis and Polymyalgia Rheumatic

Condition(s) studied

Investigational drug(s) / intervention(s)

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

Immunohistochemistry of Temporal Artery Biopsies: Immunohistochemistry staining of TAB to assess local expression of endothelial adhesion molecules in acute inflammation.

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.

Study 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.

Eligibility

Primary outcome measure(s)

• Number of Participants with Detected Neuro-Ophthalmological Manifestations — At baseline, 3 months, 6 months, 9 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
  Use of OCTA, TOS, and additional ocular imaging to assess and monitor ocular and cranial vascular abnormalities indicative of GCA. Unit of Measure: Number of participants.
• Number of Participants with Detected Cardiac and Aortic Involvement — At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
  Detection and monitoring of inflammatory changes and structural anomalies in the cardiac and aortic regions using MRI and CEUS. Unit of Measure: Number of participants.
• Changes in Immune Cell Phenotype — At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
  Identification and quantification of immune cell types including changes over time using FACS. Unit of Measure: Changes in levels (percentages).
• Changes in Cytokine Profiles — At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
  Identification and quantification of cytokines including changes over time using 3'-mRNA transcriptome analysis. Unit of Measure: Changes in levels (pg/mL).
• Levels of Siglec-9 in Blood — At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
  Measurement of Siglec-9 levels on immune cells including changes over time using FACS. Correlation with clinical assessments of disease activity and imaging findings. Unit of Measure: Changes in levels (percentages).
• Levels of sVAP-1 in Blood — At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
  Measurement of sVAP-1 levels in blood via ELISA including changes over time. Correlation with clinical assessments of disease activity and imaging findings. Unit of Measure: Changes in levels (ng/mL).

Trial sites (1)

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