Mapping B-cell Biology Across the Cardiovascular Territories of Giant Cell Arteritis: Towards a New Therapeutic Approach (RituxiMAP GCA)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- University of Edinburgh
- Enrollment
- 30
- Locations
- 2
- Primary Endpoint
- Quantification of vascular 89Zr-RTX uptake
Study Overview
Brief Summary
B cells are a component of the immune system which appear be important in causing all forms of cardiovascular disease. Until now, it has not been possible to directly study these cells in living patients (essential to assess their potential as the target of new treatments). For the first time in any cardiovascular disease, this study will apply cutting edge scanning technology to visualise B cells in the blood vessels of giant cell arteritis (GCA) patients. GCA is a common and potentially deadly disorder of the blood vessels which is caused by abnormalities of the immune system. Current treatments are mainly limited to steroids. Unfortunately, these drugs bring tremendous side effects and so there is an urgent requirement to discover alternatives.
Laboratory investigations tell us that B cells are highly present in GCA and so if the proposed scanning technology fails to identify these cells in the blood vessels of participants, then the technology is unlikely to be useful for other cardiovascular diseases. If, however, the study does successfully visualise B cells, this knowledge could pave the way for clinical trials of B cell targeted treatments (already established in other conditions) as steroid alternatives in GCA.
This study aims to map the distribution of the radiotracer zirconium-89 labelled rituximab within the blood vessels of patients with newly diagnosed GCA and compare this with two separate control groups without the condition. This will allow us to determine the role of B cells within this condition, and whether patients would benefit from B cell-depleting treatments such as rituximab.
Detailed Description
Giant cell arteritis (GCA) is an auto-immune condition which causes inflammation of medium and large arteries around the body. Previously thought to primarily affect the temporal arteries, there is now an understanding that the disease is more widespread, with most patients demonstrating involvement of the aorta and other large vessels.
Current treatments rely heavily on steroids which can cause significant side effects. Other novel treatments for GCA are also limited, with many patients relapsing once treatment is withdrawn. There is therefore an urgent need for new therapies for GCA, particular in those patients with large vessel involvement (LV-GCA)
B cells - a type of immune cell - are thought to play a key role in causing damage to blood vessels in diseases like atherosclerosis and may be implicated in GCA. Accordingly, a potential treatment approach may be to target B cells using a drug called rituximab (RTX), which is already used in other immune conditions. To explore this possibility safely and effectively, we need a way to see where B cells are in the body, and how they are affected by treatment in GCA. This can be achieved using total body PET scanning with zirconium-89-labeled rituximab.
By injecting patients with zirconium-89-labeled rituximab and then undergoing total body PET scanning, this study hopes to track B cells in real time within the blood vessels of those with GCA. This scan has been used safely in studies of cancer, lung disease, and rheumatoid arthritis.
In summary, the aim of this feasibility study is to:
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 50 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •For GCA group:
- •Adults ≥ 50 years at the time of enrolment
- •Meets 2022 American College of Rheumatology/EULAR classification criteria for giant cell arteritis
- •Imaging evidence of active LV-GCA in the previous 4 weeks
- •Will be managed with corticosteroid monotherapy by the standard care team.
- •For BCMID group:
- •Adults ≥ 18 years at the time of enrolment
- •Meets criteria for a diagnosis of a B-cell mediated immune disorder
- •Considered to have active disease by referring team
- •Will be managed as per standard of care by referring team
- •For AA group:
- •Adults ≥ 50 years at the time of enrolment
- •Imaging evidence of atherosclerotic aortic aneurysm
Exclusion Criteria
- •Participants receiving corticosteroids for >4 weeks immediately prior to baseline
- •Previous diagnosis of GCA
- •History of any major morbidity which the clinical investigator considers contraindicated to study entry
- •Pregnancy or breastfeeding
- •Advanced renal dysfunction (eGFR <15ml/min/1.73m2)
- •Patients without mental capacity or willingness to provide informed consent
- •Inability or unwillingness to comply with the radiation protection advice
Arms & Interventions
LV-GCA group
Patients with a diagnosis of active, large vessel GCA
Intervention: Zirconium Zr 89 labelled rituximab (Diagnostic Test)
AA control group
Patients with a diagnosis of atherosclerotic aortic aneurysm
Intervention: Zirconium Zr 89 labelled rituximab (Diagnostic Test)
BCMID control group
Patients with a diagnosis of a B-cell mediated inflammatory disorder
Intervention: Zirconium Zr 89 labelled rituximab (Diagnostic Test)
Outcomes
Primary Outcomes
Quantification of vascular 89Zr-RTX uptake
Time Frame: 0-4 months
Quantification of vascular 89Zr-RTX uptake compared between: A) those with LV-GCA before and after treatment with steroids B) those with LV-GCA and a control group
Quantification of vascular 89Zr-RTX uptake
Time Frame: 0-4 months
Quantification of vascular 89Zr-RTX uptake compared between: A) those with LV-GCA before and after treatment with steroids B) those with LV-GCA and a control group
Secondary Outcomes
- Correlation between vascular 89Zr-RTX uptake and peripheral blood B cell populations(0-4 months)
- Correlation between vascular 89Zr-RTX uptake and temporal artery B cell populations(0-4 months)
- Correlation between vascular 89Zr-RTX uptake and peripheral blood B cell populations(0-4 months)
- Correlation between vascular 89Zr-RTX uptake and temporal artery B cell populations(0-4 months)