Assessing Biomarker in Giant Cell Arteritis and Polymyalgia Rheumatic (GCAIO)

April 7, 2025 updated by: Valentin Schäfer, University of Bonn

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The GCAIO study focuses on patients with newly diagnosed GCA and PMR or those experiencing a flare-up. The primary sites for patient recruitment include the ophthalmological and rheumatological departments of the University Hospital of Bonn, Germany. Additional participants can be referred by local rheumatologists and primary care physicians. Healthy controls are recruited through the ophthalmological and rheumatological department of the University Hospital Bonn.

Description

Inclusion Criteria:

  • Informed Consent: Participants (>18 years) must provide written informed consent to voluntarily participate in the study.
  • Confirmed Diagnosis: Diagnosis of GCA or PMR confirmed by the treating physician and fulfilling expanded ACR-EULAR classification criteria. Patients must have been either newly diagnosed within the last three days or have experienced a disease flare within the same timeframe.

Exclusion Criteria:

  • Severe Renal Insufficiency: Chronic glomerular filtration rate (GFR) less than 30 mL/min.
  • Other Medical Conditions Requiring Glucocorticoids: Presence of medical conditions other than GCA or PMR that necessitate continuous or intermittent treatment with oral or parenteral glucocorticoids.
  • Other Inflammatory Rheumatic Diseases: Patients with other inflammatory rheumatic diseases.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
PMR/ GCA
Patients diagnosed with GCA and/or PMR will be enrolled in this cohort. They will undergo a series of interventions including immunological profiling (cytokine profiling and immune cell phenotyping using flow cytometry, ELISA, 3'mRNA sequencing, high content analysis via a cell-based ex-vivo assay), and diagnostic imaging (MRI, OCTA including further ophthalmological assessment, vascular and transorbital ultrasound. Samples will be collected from patients at various stages of the disease (t=0, t=6, t=12, t=18 months, during flare-ups). Furthermore, TAB will be stained with a VAP-1 antibody to assess the expression and localization of VAP-1 in the arterial tissue.
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.
Other Names:
  • Aortic/ cardiac MRI
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.
Other Names:
  • TOS
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.
Other Names:
  • CEUS
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.
Other Names:
  • OCTA
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.
Other Names:
  • GCAIO-essay
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.
Other Names:
  • ELISA
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.
Other Names:
  • FACS
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.
Other Names:
  • IHC TAB
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.
Control Group
Age- and gender-matched healthy subjects will serve as the control group to provide baseline data for comparative purposes. This group will not receive any treatment related to GCA or PMR but undergoes similar diagnostic procedures for baseline measurements, including imaging and immunological assessments.
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.
Other Names:
  • Aortic/ cardiac MRI
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.
Other Names:
  • TOS
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.
Other Names:
  • CEUS
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.
Other Names:
  • OCTA
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.
Other Names:
  • GCAIO-essay
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.
Other Names:
  • ELISA
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.
Other Names:
  • FACS
Diagnostic test: Laboratory assessment:
Serum Chemistry (nt-proBNP, troponin T, CRP, ESR, blood count)
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with Detected Neuro-Ophthalmological Manifestations
Time Frame: 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.
At baseline, 3 months, 6 months, 9 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
Number of Participants with Detected Cardiac and Aortic Involvement
Time Frame: 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.
At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
Changes in Immune Cell Phenotype
Time Frame: 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).
At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
Changes in Cytokine Profiles
Time Frame: 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).
At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
Levels of Siglec-9 in Blood
Time Frame: 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).
At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
Levels of sVAP-1 in Blood
Time Frame: 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).
At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Bonn

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2023

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2027

Study Registration Dates

First Submitted

May 5, 2024

First Submitted That Met QC Criteria

June 10, 2024

First Posted (Actual)

June 14, 2024

Study Record Updates

Last Update Posted (Actual)

April 10, 2025

Last Update Submitted That Met QC Criteria

April 7, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 321/22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Data are available upon reasonable request from the corresponding investigator.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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