Evaluation of Ultrasound and PET/CT in the Diagnosis and Monitoring of Giant Cell Arteritis

Giant Cell Arteritis Clinical Trial

Official title:

Evaluation of Ultrasound and PET/CT in the Diagnosis and Monitoring of Giant Cell Arteritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03765424
• Other study ID #: ULvsPET GCA cohort
• Status: Completed
• Start date: October 1, 2014
• Est. completion date: December 31, 2018

Study information

• Verified date: November 2018
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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)

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: December 31, 2018
• Est. primary completion date: July 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arteritis
• Giant Cell Arteritis
• Polymyalgia Rheumatica
• Vasculitis

Intervention

Diagnostic Test:
• Ultrasound
Ultraosund of temporal, carotid and axillary arteries

Locations

Country	Name	City	State
n/a

Sponsors (5)

Lead Sponsor	Collaborator
University of Aarhus	Aase and Ejnar Danielsens Foundation, AP Moeller Foundation, Hartmann Fonden, The Danish Rheumatism Association

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient global NRS	Patients global experience of disease activity on a numerical range scale (0-10)	Baseline, day 10, week 8, 24 and 15 months
Other	Physician NRS	Physicians global judgement of disease activity on a numerical range scale (0-10)	Baseline, day 10, week 8, 24 and 15 months
Other	CRP	c-reactive protein (mg/l)	Baseline, day 3 and 10, week 8, 24 and 15 months
Other	Physicians judgement of disease activity	Overall judgement of disease activity (remission, possible activity not requiring treatment, activity/relapse)	Baseline, day 10, week 8, 24 and 15 months
Other	Cumulated glucocorticoid dose	Cumulated glucocorticoid dose (mg)	Baseline, day 10, week 8, 24 and 15 months
Other	Glucocorticoid dose	Glucocorticoid dose (mg)	Baseline, day 10, week 8, 24 and 15 months
Other	Cardiovascular events	Cardiovascular events (number)	4-5 years
Primary	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.	Time of diagnosis/pre-treatment
Secondary	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	Time of diagnosis/pre-treatment
Secondary	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.	Time of diagnosis/pre-treatment
Secondary	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.	3 days, 10 days and 8 weeks after initiated treatment
Secondary	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	Time of diagnosis/pre-treatment
Secondary	Temporal artery biopsy	Temporal artery biopsy considered positive in the presence of an inflammatory infiltrate in any vessel wall layer	Time of diagnosis
Secondary	Halo sign for monitoring disease activity (week 8, 24 and 15 months)	Presence or absence of halos on US	week 8, 24 and 15 months after initiated treatment
Secondary	Composite halo score for monitoring disease activity (week 8, 24 and 15 months)	Composite halo score	week 8, 24 and 15 months after initiated treatment
Secondary	Intima media thickness for monitoring disease activity (week 8, 24 and 15 months)	Maximum intima media thickness (IMT) measurement on US	week 8, 24 and 15 months after initiated treatment
Secondary	PETVAS for monitoring disease activity (15 months)	Composite PET scores (e.g.PETVAS)	15 months after treatment is initiated
Secondary	Semiquantitative FDG measure for monitoring disease activity (15 months)	Maximum semiquantitative FDG measures	15 months after treatment is initiated
Secondary	FDG burden for monitoring disease activity (15 months)	Composite scores of FDG inflammatory burden (summarising FDG uptake in voxels of interest)	15 months after treatment is initiated
Secondary	PETVAS for GCA prognosis (baseline)	PETVAS score (summarising graded (1-4) FDG uptake in arterial vessel segments)	4-5 years after diagnosis
Secondary	Semiquantitative FDG measure for GCA prognosis (baseline)	Maximum semiquantitative FDG measures	4-5 years after diagnosis
Secondary	FDG burden for GCA prognosis (baseline)	Composite scores of arterial FDG uptake (summarising FDG uptake in voxels of interest)	4-5 years after diagnosis
Secondary	Aortic diameter 4-5 years after diagnosis	Aortic diameter on cross sectional imaging	4-5 years after diagnosis
Secondary	Vessel wall thickening 4-5 years after diagnosis	Vessel wall thickening	4-5 years after diagnosis