Primary Objective: to evaluate arterial [18F]fluor-PEG-folate uptake on PET/CT in patients with active, large vessel GCA; and in the same patients after 9 months of standard treatment.Secondary objectives are:- Assessment of the relationship between…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Our main endpoint is the visualization of inflamed arteries at baseline and
after 9 months of standard treatment.
Secondary outcome
Our secondary endpoints are the association between [18F]fluor-PEG-folate
uptake after 9 months of treatment and clinical disease activity at that time
point and the development of relapses during the first 9 months of treatment.
Background summary
Giant Cell Arteritis (GCA) is a chronic systemic inflammatory disease that
primarily affects the large and medium-sized arteries. The inflammation is
usually chronic, and may lead to ischemic complication due to
occlusion/stenosis. A late complication is the development of aortic aneurysms.
Standard treatment consists of high-dose glucocorticoids which are tapered
within 1-1.5 years. Symptoms, physical signs and laboratory tests are not
specific for GCA. Recent international guidelines therefore emphasize the
importance of imaging as a diagnostic tool for visualizing vessel wall
inflammation in GCA. Imaging might help to establish the initial diagnosis of
GCA and to estimate disease activity during follow-up. An adequate diagnosis
and proper disease monitoring are essential to prevent the development of
complications of GCA, while minimising unnecessary exposure to
immunosuppressive treatment. Currently, the fluorine-18-deoxyglucose positron
assemission tomography/computer tomography (FDG-PET/CT) is used as diagnostic
imaging modality in GCA. FDG-PET/CT visualises tissues with high glucose
metabolism, including tissues that are inflamed. One of the drawbacks of the
FDG-PET/CT is the substantial decrease in sensitivity after 3 days of
glucocorticoid treatment. Another disadvantage is its reliance on glucose
metabolism. This further limits FDG-PET/CT scanning in patients with poorly
controlled diabetes, a known complication of glucocorticoid treatment.
Furthermore, arteries with a close relation to metabolically active organs
(such as the brain) cannot be evaluated by the FDG-PET/CT scan.
An alternative approach might be to visualize specific immune cells in the
arterial wall of patients with GCA. Biopsy studies indicate that macrophages
could be an excellent target for such imaging studies. Recently, the novel
macrophage tracer [18F]fluor-polyetyhylene glycol (PEG)-folate has been
developed for PET/CT imaging by the VU Medical Center. [18F]fluor-PEG-folate
binds to the β-isoform of the folate receptor (FRβ). The [18F] tracer is
stable, which allows for synthesis in a central GMP laboratory from where it
can be shipped to other hospitals. [18F]fluor-PEG-folate has shown an excellent
ability to detect macrophages in inflamed joints, both in an animal model of
inflammatory arthritis, as well as in humans with rheumatoid arthritis.
Importantly, biopsy studies haver shown that FRβ-expressing macrophages are
abundant in the inflamed arteries of patients with GCA .
Study objective
Primary Objective: to evaluate arterial [18F]fluor-PEG-folate uptake on PET/CT
in patients with active, large vessel GCA; and in the same patients after 9
months of standard treatment.
Secondary objectives are:
- Assessment of the relationship between the [18F]fluor-PEG-folate uptake after
9 months of treatment and clinical disease activity at that time point.
- Assessment of the relationship between the [18F]fluor-PEG-folate uptake after
9 months of treatment and the development of relapses during the first 9 months
of treatment.
Study design
A multicentre (UMCG and VU Medical Center), prospective cohort study.
Study burden and risks
The total radiation burden per PET-CT scan per patient will be at 6.2 mSv.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
-Age >= 50 years.
-ESR >=50 mm/hr (by Westergren method) or CRP >= 24.5 mg/L.
-Clinical symptoms of GCA (at least one of the following): unequivocal cranial
symptoms of GCA, symptoms of polymyalgia rheumatica or constitutional symptoms.
-Imaging findings consistent with GCA (at least by one of the following
methods): ultrasound, FDG-PET/CT, MRA or CTA.
-Patients must be able to adhere to the study appointments and other protocol
requirements.
-Patients must be capable of giving informed consent and the consent must have
been obtained prior to the study related procedures.
Exclusion criteria
- Clinical symptoms suggestive of cranial GCA (at least one of the
following): new-onset localized headache, scalp tenderness, temporal
artery abnormality (thickening, tenderness, and/or decreased
pulsation), ischemia-related vision loss, stroke, transients ischemic
attack, jaw or tongue claudication (pain upon mastication).
- Ultrasound findings consistent with cranial GCA (e.g. halo sign in
temporal or facial artery).
- A prior positive temporal artery biopsy.
- Initiation or dose escalation of systemic glucocorticoid therapy (oral,
IM, IV) in the 4 weeks prior to inclusion
- Initiation or dose escalation of disease-modifying antirheumatic drugs
(DMARDs) within 3 months prior to inclusion
- Treatment with any investigational drug within 3 months prior to
inclusion.
- Females with child bearing potential. Post-menopausal women with
>12 months of amenorrhoea are considered to have no child bearing
potential. Given the age distribution of patients with GCA, exclusion of
females with child bearing potential will not lead to recruitment bias in
the study.
- Research-related radiation exposure (cumulative >=5 mSv) in the year
before inclusion.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-001019-26-NL |
| CCMO | NL73549.042.20 |