NCT06460142

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for all trials

Timeline
17mo left

Started Sep 2023

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress66%
Sep 2023Sep 2027

Study Start

First participant enrolled

September 1, 2023

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

May 5, 2024

Completed
1 month until next milestone

First Posted

Study publicly available on registry

June 14, 2024

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2026

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2027

Last Updated

April 10, 2025

Status Verified

April 1, 2025

Enrollment Period

3.1 years

First QC Date

May 5, 2024

Last Update Submit

April 7, 2025

Conditions

Keywords

Giant Cell ArteritisPolymyalgia RheumaticaVasculitisInflammatory DisordersClinical BiomarkersPredictive BiomarkersDisease Activity MonitoringTherapeutic ResponseDiagnostic Imaging TechniquesAortic ImagingMagnetic Resonance Imaging (MRI)Vascular UltrasoundOptical Coherence Tomography Angiography (OCT-A)Transcriptome AnalysisVascular-adhesion protein 1Positron emission tomography-computed tomography (PET/CT)Siglec-9

Outcome Measures

Primary Outcomes (6)

  • Number of Participants with Detected Neuro-Ophthalmological Manifestations

    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

    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

    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

    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

    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

    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).

Study Arms (2)

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 imagingDiagnostic Test: Vascular ultrasoundDiagnostic Test: Transorbital UltrasoundDiagnostic Test: Contrast-Enhanced UltrasoundDiagnostic Test: Optical coherence tomography angiographyDiagnostic Test: Fluorescein angiographyDiagnostic Test: Fundus autofluorescenceDiagnostic Test: Color Fundus PhotographyDiagnostic Test: Cell-based ex-vivo assay with high-content analysisDiagnostic Test: 3'mRNA sequencingDiagnostic Test: Enzyme-linked immunosorbent assayDiagnostic Test: Flow cytometryDiagnostic Test: Laboratory assessment:Diagnostic Test: Immunohistochemistry of Temporal Artery BiopsiesDiagnostic Test: Functional assessment questionnaires

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 imagingDiagnostic Test: Vascular ultrasoundDiagnostic Test: Transorbital UltrasoundDiagnostic Test: Contrast-Enhanced UltrasoundDiagnostic Test: Optical coherence tomography angiographyDiagnostic Test: Fluorescein angiographyDiagnostic Test: Fundus autofluorescenceDiagnostic Test: Color Fundus PhotographyDiagnostic Test: Cell-based ex-vivo assay with high-content analysisDiagnostic Test: 3'mRNA sequencingDiagnostic Test: Enzyme-linked immunosorbent assayDiagnostic Test: Flow cytometryDiagnostic Test: Laboratory assessment:Diagnostic Test: Functional assessment questionnaires

Interventions

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

Also known as: Aortic/ cardiac MRI
Control GroupPMR/ GCA
Vascular ultrasoundDIAGNOSTIC_TEST

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

Control GroupPMR/ GCA

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.

Also known as: TOS
Control GroupPMR/ GCA

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

Also known as: CEUS
Control GroupPMR/ GCA

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.

Also known as: OCTA
Control GroupPMR/ GCA

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.

Control GroupPMR/ GCA

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.

Control GroupPMR/ GCA

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.

Control GroupPMR/ GCA

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

Also known as: GCAIO-essay
Control GroupPMR/ GCA
3'mRNA sequencingDIAGNOSTIC_TEST

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.

Control GroupPMR/ GCA

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.

Also known as: ELISA
Control GroupPMR/ GCA
Flow cytometryDIAGNOSTIC_TEST

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.

Also known as: FACS
Control GroupPMR/ GCA
Laboratory assessment:DIAGNOSTIC_TEST

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

Control GroupPMR/ GCA

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

Also known as: IHC TAB
PMR/ GCA

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 GroupPMR/ GCA

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-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.

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital Bonn

Bonn, North Rhine-Westphalia, 53127, Germany

RECRUITING

Related Links

Biospecimen

Retention: SAMPLES WITH DNA

PBMC, Pax-Tube, Serum, Temporal artery biopsy.

MeSH Terms

Conditions

Giant Cell ArteritisPolymyalgia RheumaticaVasculitis

Interventions

Fluorescein AngiographyOptical ImagingFlow CytometryImmunohistochemistry

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous SystemAutoimmune Diseases of the Nervous SystemNervous System DiseasesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesVascular DiseasesCardiovascular DiseasesArteritisSkin Diseases, VascularSkin DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System DiseasesMuscular DiseasesMusculoskeletal DiseasesRheumatic DiseasesConnective Tissue Diseases

Intervention Hierarchy (Ancestors)

AngiographyDiagnostic Techniques, CardiovascularDiagnostic Techniques and ProceduresDiagnosisDiagnostic Techniques, OphthalmologicalDiagnostic ImagingInvestigative TechniquesCell SeparationCytological TechniquesClinical Laboratory TechniquesCytophotometryFluorometryLuminescent MeasurementsPhotometryChemistry Techniques, AnalyticalHistocytochemistryHistological TechniquesImmunologic Techniques

Study Officials

  • Valentin S. Schäfer, Univ. Prof.

    Department of Rheumatology and Clinical Immunology, University Hospital Bonn

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Simon M. Petzinna, Dr. med.

CONTACT

Valentin S. Schäfer, Univ. Prof.

CONTACT

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Univ. Prof. Dr. med. Valentin Sebastian Schäfer

Study Record Dates

First Submitted

May 5, 2024

First Posted

June 14, 2024

Study Start

September 1, 2023

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2027

Last Updated

April 10, 2025

Record last verified: 2025-04

Locations