Clinical trial NCT03765424: Evaluation of Ultrasound and PET/CT in the Diagnosis and Monitoring of Giant Cell Arteritis
Official title: Evaluation of Ultrasound and PET/CT in the Diagnosis and Monitoring of Giant Cell Arteritis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Giant Cell Arteritis
Vasculitis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: The Danish Rheumatism Association
name: Hartmann Fonden
name: AP Moeller Foundation
name: Aase and Ejnar Danielsens Foundation
First posted: 2018-12-05
Enrollment: 101
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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.

Brief 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.

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)

Eligibility criteria: Inclusion Criteria:

1. Age more than 50 years
2. C-reactive protein (CRP)\>15 mg/L or erythrocyte sedimentation rate (ESR)\>40 mm/h
3. Either

   1. cranial symptoms such as new-onset headache or scalp tenderness, jaw or tongue claudication, visual disturbances
   2. new-onset limb claudication
   3. protracted constitutional symptoms, defined as weight loss\>5 kilograms or fever\>38 degrees Celcius for \>3 weeks
   4. Bilateral shoulder pain and morning stiffness.

Exclusion Criteria:

1. oral glucocorticoid treatment within the past month;
2. subcutaneous, intramuscular, intra-articular or intravenous glucocorticoid within the past 2 months;
3. DMARD treatment or other immunosuppressive therapy within the past 3 months;
4. ongoing treatment with interleukin2;
5. previous diagnosis of GCA or polymyalgia rheumatica;
6. 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.

Primary outcomes:
measure: Diagnostic accuracy of large vessel ultrasound with PET/CT as reference
timeFrame: Time of diagnosis/pre-treatment
Secondary outcomes:
measure: Large vessel intima-media thickness (IMT) cut off for LV-GCA diagnosis with PET/CT as reference
timeFrame: Time of diagnosis/pre-treatment
measure: Diagnostic accuracy vascular ultrasound (overall)
timeFrame: Time of diagnosis/pre-treatment
measure: Diagnostic accuracy of vascular ultrasound after treatment (day 3, 10 and week 8)
timeFrame: 3 days, 10 days and 8 weeks after initiated treatment
measure: Diagnostic accuracy of PET/CT of cranial arteries for c-GCA diagnosis (reference: American College of Rheumatology 1990 criteria)
timeFrame: Time of diagnosis/pre-treatment
measure: Temporal artery biopsy
timeFrame: Time of diagnosis
measure: Halo sign for monitoring disease activity (week 8, 24 and 15 months)
timeFrame: week 8, 24 and 15 months after initiated treatment
measure: Composite halo score for monitoring disease activity (week 8, 24 and 15 months)
timeFrame: week 8, 24 and 15 months after initiated treatment
measure: Intima media thickness for monitoring disease activity (week 8, 24 and 15 months)
timeFrame: week 8, 24 and 15 months after initiated treatment
measure: PETVAS for monitoring disease activity (15 months)
timeFrame: 15 months after treatment is initiated
measure: Semiquantitative FDG measure for monitoring disease activity (15 months)
timeFrame: 15 months after treatment is initiated
measure: FDG burden for monitoring disease activity (15 months)
timeFrame: 15 months after treatment is initiated
measure: PETVAS for GCA prognosis (baseline)
timeFrame: 4-5 years after diagnosis
measure: Semiquantitative FDG measure for GCA prognosis (baseline)
timeFrame: 4-5 years after diagnosis
measure: FDG burden for GCA prognosis (baseline)
timeFrame: 4-5 years after diagnosis
measure: Aortic diameter 4-5 years after diagnosis
timeFrame: 4-5 years after diagnosis
measure: Vessel wall thickening 4-5 years after diagnosis
timeFrame: 4-5 years after diagnosis
Other outcomes:
measure: Patient global NRS
timeFrame: Baseline, day 10, week 8, 24 and 15 months
measure: Physician NRS
timeFrame: Baseline, day 10, week 8, 24 and 15 months
measure: CRP
timeFrame: Baseline, day 3 and 10, week 8, 24 and 15 months
measure: Physicians judgement of disease activity
timeFrame: Baseline, day 10, week 8, 24 and 15 months
measure: Cumulated glucocorticoid dose
timeFrame: Baseline, day 10, week 8, 24 and 15 months
measure: Glucocorticoid dose
timeFrame: Baseline, day 10, week 8, 24 and 15 months
measure: Cardiovascular events
timeFrame: 4-5 years
Locations:
Study officials:
affiliation: Department of Rheumatology
name: Berit Nielsen, MD
role: PRINCIPAL_INVESTIGATOR
References: