Giant Cell ArteritisNCT03765424
Evaluation of Ultrasound and PET/CT in the Diagnosis and Monitoring of Giant Cell Arteritis
An observational study of Giant Cell Arteritis and Vasculitis, run by University of Aarhus.
Trial summary
The aim of this project is to prospectively evaluate the diagnostic accuracy of different imaging tools in specific giant cell arteritis disease subsets before and after treatment initiation. Diagnostic tools with high sensitivity and specificity are a prerequisite for optimal treatment of GCA patients. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Giant Cell Arteritis, Vasculitis
- What is being tested?
- Ultrasound
- How many people
- 101 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2014to 31 Dec 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: For the GCA suspect cohort, patients referred to Department of Rheumatology, Aarhus University Hospital due to suspicion of GCA are considered for inclusion. Patients in whom a 18F-FDG PET/CT is not performed by the time of referral and who presents with unequivocal cranial symptoms of GCA requiring acute initiation of GC treatment are not considered for inclusion.
Who may be able to join
- Age more than 50 years
- C-reactive protein (CRP)>15 mg/L or erythrocyte sedimentation rate (ESR)>40 mm/h
- Either
- cranial symptoms such as new-onset headache or scalp tenderness, jaw or tongue claudication, visual disturbances
- new-onset limb claudication
- protracted constitutional symptoms, defined as weight loss>5 kilograms or fever>38 degrees Celcius for >3 weeks
- Bilateral shoulder pain and morning stiffness.
Who cannot join
- oral glucocorticoid treatment within the past month;
- subcutaneous, intramuscular, intra-articular or intravenous glucocorticoid within the past 2 months;
- DMARD treatment or other immunosuppressive therapy within the past 3 months;
- ongoing treatment with interleukin2;
- previous diagnosis of GCA or polymyalgia rheumatica;
- any disease potentially causing large vessel inflammation, that is autoimmune diseases; rheumatoid arthritis, Cogans syndrome, relapsing polychondritis, ankylosing spondylitis, systemic lupus erythematosus, Buerger's disease, Bechet's disease, inflammatory bowel disease, infections; syphilis, known active current or history of recurrent tuberculosis, hepatitis or HIV, or other large vessel disease; sarcoidosis, neurofibromatosis, congenital coarctation, Marfans syndrome, Ehlers-Danlos syndrome, retroperitoneal fibrosis.
About this study
The aim of this project is to prospectively evaluate the diagnostic accuracy of different imaging tools in specific giant cell arteritis disease subsets before and after treatment initiation. Diagnostic tools with high sensitivity and specificity are a prerequisite for optimal treatment of GCA patients.
Specifically, the diagnostic accuracy of ultrasound (US) as compared to 18F-FDG PET/CT in new-onset, treatment naïve large vessel(LV)-GCA patients is investigated. Furthermore, long-term follow up including US, 18F-FDG PET/CT and cross sectional imaging is performed to explore the potential of imaging as monitoring and prognostic tools.
In this observational cohort, the diagnostic accuracy of 18F-FDG PET/CT after three and ten days of glucocorticoid treatment in the subset of LV-GCA patients and the diagnostic accuracy of 18F-FDG PET/CT in cranial artery inflammation in new-onset, treatment naïve c-GCA patients as compared to a control group of patients with a previous diagnosis of malignant melanoma was also evaluated and is registered elsewhere (ClinicalTrials.gov Identifier: NCT03285945 and NCT03409913, respectively)
Read the detailed description
The diagnosis of GCA is clinical and syndrome-based. Only few years ago, temporal artery biopsy (TAB) was the standard diagnostic tool to confirm diagnosis, although sensitivity is moderate[3,4] and its outcome seldom affects treatment management[5]. Today, the European League Against Rheumatism (EULAR) recommends diagnostic imaging in all patients suspected of GCA[6]. The imaging of choice is based on the suspected vessel involvement. In patients suspected of cranial GCA (c-GCA), vascular ultrasound (US) is the recommended first line imaging test, whereas Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emissions tomography/computed tomography (PET/CT) is not recommended for the assessment of cranial arteries.
In patients suspected of large vessel involvement (LV-GCA), 18F-FDG PET/CT, US, magnetic resonance imaging (MRI) or CT can be used to confirm disease, but no specific priority of the imaging tests is given. US is an attractive first line imaging in LV-GCA suspected patients since it is increasingly used in the diagnosis of c-GCA, is readily available and cheap. 18F-FDG PET/CT is an appealing diagnostic tool in LV-GCA suspected patients, since it also evaluates malignancy and infection, differential diagnoses often considered in this disease subset. However, 18F-FDG PET/CT is often not readily available, is expensive and exposes patients to radiation. Moreover, its sensitivity seems to decrease with glucocorticoid (GC) treatment and the window of opportunity in which sensitivity is unaffected is unknown.
Relapse during glucocorticoid tapering is frequent in GCA. However, the evaluation of potential GCA disease activity relies on unspecific symptoms and inflammatory biomarkers. There is a significant overlap between symptoms of GCA disease activity and GC adverse effect and the same holds for symptoms and biomarkers of disease activity and infection, making the evaluation difficult. Accurate tools to support treatment decisions, avoid over-treatment without risk of GCA related complications are lacking.
The aim of this project is to prospectively evaluate the diagnostic accuracy of different imaging tools in specific giant cell arteritis disease subsets before and after treatment initiation. Diagnostic tools with high sensitivity and specificity are a prerequisite for optimal treatment of GCA patients.
Specifically, the diagnostic accuracy of ultrasound (US) as compared to 18F-FDG PET/CT in new-onset, treatment naïve large vessel(LV)-GCA patients is investigated. Furthermore, long-term follow up including US, 18F-FDG PET/CT and cross sectional imaging is performed to explore the potential of imaging as monitoring and prognostic tools.
In this observational cohort, the diagnostic accuracy of 18F-FDG PET/CT after three and ten days of glucocorticoid treatment in the subset of LV-GCA patients and the diagnostic accuracy of 18F-FDG PET/CT in cranial artery inflammation in new-onset, treatment naïve c-GCA patients as compared to a control group of patients with a previous diagnosis of malignant melanoma was also evaluated and is registered elsewhere (ClinicalTrials.gov Identifier: NCT03285945 and NCT03409913, respectively)
- Conditions
- Giant Cell Arteritis, Vasculitis
- Being tested
- Ultrasound
- Medical subject headings
- Giant Cell Arteritis, Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UltrasoundDiagnostic test
Ultraosund of temporal, carotid and axillary arteries
| Study group | Role | What they receive |
|---|---|---|
| GCA cases | GCA cases were patients with a clinical diagnosis of GCA based on a rheumatologists evaluation of history taking, physical examination, laboratory screening and initial PET report (reporting potential large vessel inflammation but not considering cranial artery inflammation).
GCA was considered large vessel (LV) and/or cranial (c) GCA cases:
LV-GCA cases were patients with a clinical diagnosis of GCA and verified LV inflammation by 18F-FDG PET/CT with or without concomitant c-GCA.
C-GCA cases, for the exploratory analysis of the performance of US and PET in c-GCA, were patients with a clinical diagnosis of GCA fulfilling the 1990 American College of Rheumatology (ACR) criteria, with or without concomitant LV-GCA. Receives: Diagnostic Test: Ultrasound | |
| controls | Controls were GCA suspected patients in whom GCA diagnosis was dismissed. Receives: Diagnostic Test: Ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic accuracy of large vessel ultrasound with PET/CT as reference
Large vessel ultrasound for LV-GCA diagnosis is considered positive in the presence of a halo in carotid and/or axillary arteries.
Measured: Time of diagnosis/pre-treatment
Secondary outcomes (16)
Large vessel intima-media thickness (IMT) cut off for LV-GCA diagnosis with PET/CT as reference
IMT measurement performed on the distal vessel wall in carotid and axillary arteries
Measured: Time of diagnosis/pre-treatment
Diagnostic accuracy vascular ultrasound (overall)
Vascular ultrasound for GCA diagnosis is considered positive in the presence of a halo in temporal, carotid and/or axillary arteries.
Measured: Time of diagnosis/pre-treatment
Diagnostic accuracy of vascular ultrasound after treatment (day 3, 10 and week 8)
Vascular ultrasound for GCA diagnosis is considered positive in the presence of a halo in temporal, carotid and/or axillary arteries.
Measured: 3 days, 10 days and 8 weeks after initiated treatment
Diagnostic accuracy of PET/CT of cranial arteries for c-GCA diagnosis (reference: American College of Rheumatology 1990 criteria)
cranial artery (vertebral, maxillary and temporal) FDG uptake above surrounding tissue FDG uptake is considered consistent with vasculitis
Measured: Time of diagnosis/pre-treatment
Temporal artery biopsy
Temporal artery biopsy considered positive in the presence of an inflammatory infiltrate in any vessel wall layer
Measured: Time of diagnosis
Halo sign for monitoring disease activity (week 8, 24 and 15 months)
Presence or absence of halos on US
Measured: week 8, 24 and 15 months after initiated treatment
Composite halo score for monitoring disease activity (week 8, 24 and 15 months)
Composite halo score
Measured: week 8, 24 and 15 months after initiated treatment
Intima media thickness for monitoring disease activity (week 8, 24 and 15 months)
Maximum intima media thickness (IMT) measurement on US
Measured: week 8, 24 and 15 months after initiated treatment
PETVAS for monitoring disease activity (15 months)
Composite PET scores (e.g.PETVAS)
Measured: 15 months after treatment is initiated
Semiquantitative FDG measure for monitoring disease activity (15 months)
Maximum semiquantitative FDG measures
Measured: 15 months after treatment is initiated
FDG burden for monitoring disease activity (15 months)
Composite scores of FDG inflammatory burden (summarising FDG uptake in voxels of interest)
Measured: 15 months after treatment is initiated
PETVAS for GCA prognosis (baseline)
PETVAS score (summarising graded (1-4) FDG uptake in arterial vessel segments)
Measured: 4-5 years after diagnosis
Semiquantitative FDG measure for GCA prognosis (baseline)
Maximum semiquantitative FDG measures
Measured: 4-5 years after diagnosis
FDG burden for GCA prognosis (baseline)
Composite scores of arterial FDG uptake (summarising FDG uptake in voxels of interest)
Measured: 4-5 years after diagnosis
Aortic diameter 4-5 years after diagnosis
Aortic diameter on cross sectional imaging
Measured: 4-5 years after diagnosis
Vessel wall thickening 4-5 years after diagnosis
Vessel wall thickening
Measured: 4-5 years after diagnosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2018
- Study start1 Oct 2014
- Primary completion1 Jul 2018
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Giant Cell ArteritisStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- The Danish Rheumatism Association, Hartmann Fonden, AP Moeller Foundation, Aase and Ejnar Danielsens Foundation
- Responsible party
- Sponsor
- Investigators
- Berit Nielsen, MD, Principal investigator, Department of Rheumatology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03765424
- Sponsor's protocol ID
- ULvsPET GCA cohort
- Status last verified
- Nov 2018
- First submitted
- 28 Nov 2018
- Last updated
- 4 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Ultrasound and PET/CT in the Diagnosis and Monitoring of Giant Cell Arteritis
- ClinicalTrials.gov ID
- NCT03765424
- Acronym / sponsor ID
- ULvsPET GCA cohort
- Conditions
- Giant Cell Arteritis, Vasculitis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- The Danish Rheumatism Association, Hartmann Fonden, AP Moeller Foundation, Aase and Ejnar Danielsens Foundation
- Study start
- 1 Oct 2014 (actual)
- Primary completion
- 1 Jul 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 5 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this project is to prospectively evaluate the diagnostic accuracy of different imaging tools in specific giant cell arteritis disease subsets before and after treatment initiation. Diagnostic tools with high sensitivity and specificity are a prerequisite for optimal treatment of GCA patients.
Specifically, the diagnostic accuracy of ultrasound (US) as compared to 18F-FDG PET/CT in new-onset, treatment naïve large vessel(LV)-GCA patients is investigated. Furthermore, long-term follow up including US, 18F-FDG PET/CT and cross sectional imaging is performed to explore the potential of imaging as monitoring and prognostic tools.
In this observational cohort, the diagnostic accuracy of 18F-FDG PET/CT after three and ten days of glucocorticoid treatment in the subset of LV-GCA patients and the diagnostic accuracy of 18F-FDG PET/CT in cranial artery inflammation in new-onset, treatment naïve c-GCA patients as compared to a control group of patients with a previous diagnosis of malignant melanoma was also evaluated and is registered elsewhere (ClinicalTrials.gov Identifier: NCT03285945 and NCT03409913, respectively)
Detailed description
The diagnosis of GCA is clinical and syndrome-based. Only few years ago, temporal artery biopsy (TAB) was the standard diagnostic tool to confirm diagnosis, although sensitivity is moderate[3,4] and its outcome seldom affects treatment management[5]. Today, the European League Against Rheumatism (EULAR) recommends diagnostic imaging in all patients suspected of GCA[6]. The imaging of choice is based on the suspected vessel involvement. In patients suspected of cranial GCA (c-GCA), vascular ultrasound (US) is the recommended first line imaging test, whereas Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emissions tomography/computed tomography (PET/CT) is not recommended for the assessment of cranial arteries.
In patients suspected of large vessel involvement (LV-GCA), 18F-FDG PET/CT, US, magnetic resonance imaging (MRI) or CT can be used to confirm disease, but no specific priority of the imaging tests is given. US is an attractive first line imaging in LV-GCA suspected patients since it is increasingly used in the diagnosis of c-GCA, is readily available and cheap. 18F-FDG PET/CT is an appealing diagnostic tool in LV-GCA suspected patients, since it also evaluates malignancy and infection, differential diagnoses often considered in this disease subset. However, 18F-FDG PET/CT is often not readily available, is expensive and exposes patients to radiation. Moreover, its sensitivity seems to decrease with glucocorticoid (GC) treatment and the window of opportunity in which sensitivity is unaffected is unknown.
Relapse during glucocorticoid tapering is frequent in GCA. However, the evaluation of potential GCA disease activity relies on unspecific symptoms and inflammatory biomarkers. There is a significant overlap between symptoms of GCA disease activity and GC adverse effect and the same holds for symptoms and biomarkers of disease activity and infection, making the evaluation difficult. Accurate tools to support treatment decisions, avoid over-treatment without risk of GCA related complications are lacking.
The aim of this project is to prospectively evaluate the diagnostic accuracy of different imaging tools in specific giant cell arteritis disease subsets before and after treatment initiation. Diagnostic tools with high sensitivity and specificity are a prerequisite for optimal treatment of GCA patients.
Specifically, the diagnostic accuracy of ultrasound (US) as compared to 18F-FDG PET/CT in new-onset, treatment naïve large vessel(LV)-GCA patients is investigated. Furthermore, long-term follow up including US, 18F-FDG PET/CT and cross sectional imaging is performed to explore the potential of imaging as monitoring and prognostic tools.
In this observational cohort, the diagnostic accuracy of 18F-FDG PET/CT after three and ten days of glucocorticoid treatment in the subset of LV-GCA patients and the diagnostic accuracy of 18F-FDG PET/CT in cranial artery inflammation in new-onset, treatment naïve c-GCA patients as compared to a control group of patients with a previous diagnosis of malignant melanoma was also evaluated and is registered elsewhere (ClinicalTrials.gov Identifier: NCT03285945 and NCT03409913, respectively)
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GCA cases | – | Diagnostic Test: UltrasoundGCA cases were patients with a clinical diagnosis of GCA based on a rheumatologists evaluation of history taking, physical examination, laboratory screening and initial PET report (reporting potential large vessel inflammation but not considering cranial artery inflammation). GCA was considered large vessel (LV) and/or cranial (c) GCA cases: LV-GCA cases were patients with a clinical diagnosis of GCA and verified LV inflammation by 18F-FDG PET/CT with or without concomitant c-GCA. C-GCA cases, for the exploratory analysis of the performance of US and PET in c-GCA, were patients with a clinical diagnosis of GCA fulfilling the 1990 American College of Rheumatology (ACR) criteria, with or without concomitant LV-GCA. |
| controls | – | Diagnostic Test: UltrasoundControls were GCA suspected patients in whom GCA diagnosis was dismissed. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- For the GCA suspect cohort, patients referred to Department of Rheumatology, Aarhus University Hospital due to suspicion of GCA are considered for inclusion. Patients in whom a 18F-FDG PET/CT is not performed by the time of referral and who presents with unequivocal cranial symptoms of GCA requiring acute initiation of GC treatment are not considered for inclusion.
Key inclusion criteria (7 listed)
- Age more than 50 years
- C-reactive protein (CRP)>15 mg/L or erythrocyte sedimentation rate (ESR)>40 mm/h
- Either
Key exclusion criteria (6 listed)
- oral glucocorticoid treatment within the past month;
- subcutaneous, intramuscular, intra-articular or intravenous glucocorticoid within the past 2 months;
- DMARD treatment or other immunosuppressive therapy within the past 3 months;
- ongoing treatment with interleukin2;
- previous diagnosis of GCA or polymyalgia rheumatica;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UltrasoundUltraosund of temporal, carotid and axillary arteries | Diagnostic test | GCA cases, controls |
Primary outcome
Diagnostic accuracy of large vessel ultrasound with PET/CT as reference
Time frame: Time of diagnosis/pre-treatment
Large vessel ultrasound for LV-GCA diagnosis is considered positive in the presence of a halo in carotid and/or axillary arteries.
16 secondary outcomes
Large vessel intima-media thickness (IMT) cut off for LV-GCA diagnosis with PET/CT as reference
Time frame: Time of diagnosis/pre-treatment
Diagnostic accuracy vascular ultrasound (overall)
Time frame: Time of diagnosis/pre-treatment
Diagnostic accuracy of vascular ultrasound after treatment (day 3, 10 and week 8)
Time frame: 3 days, 10 days and 8 weeks after initiated treatment
Diagnostic accuracy of PET/CT of cranial arteries for c-GCA diagnosis (reference: American College of Rheumatology 1990 criteria)
Time frame: Time of diagnosis/pre-treatment
Temporal artery biopsy
Time frame: Time of diagnosis
Halo sign for monitoring disease activity (week 8, 24 and 15 months)
Time frame: week 8, 24 and 15 months after initiated treatment
Composite halo score for monitoring disease activity (week 8, 24 and 15 months)
Time frame: week 8, 24 and 15 months after initiated treatment
Intima media thickness for monitoring disease activity (week 8, 24 and 15 months)
Time frame: week 8, 24 and 15 months after initiated treatment
PETVAS for monitoring disease activity (15 months)
Time frame: 15 months after treatment is initiated
Semiquantitative FDG measure for monitoring disease activity (15 months)
Time frame: 15 months after treatment is initiated
FDG burden for monitoring disease activity (15 months)
Time frame: 15 months after treatment is initiated
PETVAS for GCA prognosis (baseline)
Time frame: 4-5 years after diagnosis
Semiquantitative FDG measure for GCA prognosis (baseline)
Time frame: 4-5 years after diagnosis
FDG burden for GCA prognosis (baseline)
Time frame: 4-5 years after diagnosis
Aortic diameter 4-5 years after diagnosis
Time frame: 4-5 years after diagnosis
Vessel wall thickening 4-5 years after diagnosis
Time frame: 4-5 years after diagnosis
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Berit Nielsen, MD principal investigator
Department of Rheumatology
Questions about this trial
What is this clinical trial studying?
An observational study of Giant Cell Arteritis and Vasculitis, run by University of Aarhus.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic accuracy of large vessel ultrasound with PET/CT as reference (time frame: Time of diagnosis/pre-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2021.