Clinical trial NCT06460142: Assessing Biomarker in Giant Cell Arteritis and Polymyalgia Rheumatic
Official title: Multimodal Assessment of Biomarkers for Diagnosing Giant Cell Arteritis and Polymyalgia Rheumatica: A Comprehensive Analysis of Clinical, Laboratory, and Imaging Profiles
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Giant Cell Arteritis
Polymyalgia Rheumatica
Keywords: Giant Cell Arteritis
Polymyalgia Rheumatica
Vasculitis
Inflammatory Disorders
Clinical Biomarkers
Predictive Biomarkers
Disease Activity Monitoring
Therapeutic Response
Diagnostic Imaging Techniques
Aortic Imaging
Magnetic Resonance Imaging (MRI)
Vascular Ultrasound
Optical Coherence Tomography Angiography (OCT-A)
Transcriptome Analysis
Vascular-adhesion protein 1
Positron emission tomography-computed tomography (PET/CT)
Siglec-9
Lead sponsor: University of Bonn
Sponsor class: OTHER
First posted: 2024-06-14
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Detected Neuro-Ophthalmological Manifestations
timeFrame: At baseline, 3 months, 6 months, 9 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
measure: Number of Participants with Detected Cardiac and Aortic Involvement
timeFrame: At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
measure: Changes in Immune Cell Phenotype
timeFrame: At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
measure: Changes in Cytokine Profiles
timeFrame: At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
measure: Levels of Siglec-9 in Blood
timeFrame: At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
measure: Levels of sVAP-1 in Blood
timeFrame: At baseline, 6 months, 12 months, 18 months, and during flare-ups (assessed up to 18 months after diagnosis).
Secondary outcomes:
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: University Hospital Bonn
state: NRW
Study officials:
affiliation: Department of Rheumatology and Clinical Immunology, University Hospital Bonn
name: Valentin S. Schäfer, Univ. Prof.
role: PRINCIPAL_INVESTIGATOR
References: