Clinical trial NCT04071691: PET Imaging of Giant Cell and Takayasu Arteritis
Official title: The PET Imaging of Giant Cell and Takayasu Arteritis Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Giant Cell Arteritis
Takayasu Arteritis
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: Cambridge University Hospitals NHS Foundation Trust
name: Wellcome Trust
name: Imperial College London
name: National Institute for Health Research, United Kingdom
First posted: 2019-08-28
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with LVV

Brief summary: While 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging is often included in the diagnostic work-up of patients with large-vessel vasculitis (LVV), 18F-FDG lacks specificity for inflammatory cells and has limited ability to track therapy response. Moreover, high background 18F-FDG uptake in the brain and myocardium largely precludes imaging temporal arteritis in giant-cell arteritis (GCA) and coronary artery involvement in Takayasu arteritis respectively. These limitations of 18F-FDG for imaging LVV highlight important unmet clinical needs, which might be overcome by using a somatostatin receptor subtype-2 (SST2) PET tracer.

Detailed description: Up-regulation of SST2 in activated macrophages represents a novel imaging target for measuring vascular inflammation, which has been previously examined in atherosclerosis using 68Ga-DOTATATE. To test the hypothesis that SST2 PET imaging can accurately identify LVV, patients with active GCA or Takayasu arteritis will undergo vascular 68Ga-DOTATATE or 18F-fluoroethyltriazole-(Tyr3)-octreotate (FETO) PET-MRI at baseline, with repeat imaging after 6 months of treatment. A group of individuals with LVV in clinical remission will also undergo SST2 PET imaging. Data from patients with clinically inactive disease will serve to confirm tracer specificity for active disease, as well as signal reproducibility. 18F-FETO is an alternative SST2 tracer to 68Ga-DOTATATE; the longer half-life and shorter positron range of 18F compared to 68Ga may offer several advantages, including wider tracer availability and improved spatial resolution when imaging small arteries. All patients will also undergo 18F-FDG imaging before treatment, where clinically indicated.

Eligibility criteria: Inclusion Criteria:

* Male or female participants \>18 years old
* Able to give written, informed consent and to lie flat
* Either:

  1. New clinical diagnosis or acute flare of LVV (Giant-cell arteritis or Takayasu's arteritis) within \~1 week of treatment initiation, and
  2. Clinical indication for 18F-FDG PET-CT scan determined by the referring physician, or
  3. Undergoing surgery for LVV, or
  4. Diagnosis of LVV in remission

Exclusion Criteria:

* Women of child bearing potential not using adequate contraception
* Contra-indication to MRI scanning
* Contrast allergy or contrast-nephropathy
* Chronic kidney disease (eGFR \<30 mL/min/1.73 m2)
* Any medical condition, in the opinion of the investigator, that prevents the participant from lying flat during scanning, or from participating in the study
* History of recent malignancy deemed relevant to the study by the investigator

Primary outcomes:
measure: Diagnostic accuracy of SST2 PET-MRI for LVV
timeFrame: Baseline
Secondary outcomes:
measure: Treatment response
timeFrame: 6 months
measure: Active versus inactive disease
timeFrame: Baseline
measure: Comparison with biochemical markers of disease severity
timeFrame: Baseline and 6 months
measure: Comparison with clinical measures of disease severity
timeFrame: Baseline and 6 months
measure: Comparison of SST2 PET tracers
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: University of Cambridge
state: Cambridgeshire
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: University of Cambridge
name: Jason M Tarkin, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tarkin JM, Joshi FR, Evans NR, Chowdhury MM, Figg NL, Shah AV, Starks LT, Martin-Garrido A, Manavaki R, Yu E, Kuc RE, Grassi L, Kreuzhuber R, Kostadima MA, Frontini M, Kirkpatrick PJ, Coughlin PA, Gopalan D, Fryer TD, Buscombe JR, Groves AM, Ouwehand WH, Bennett MR, Warburton EA, Davenport AP, Rudd JH. Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging. J Am Coll Cardiol. 2017 Apr 11;69(14):1774-1791. doi: 10.1016/j.jacc.2017.01.060.
citation: Pedersen SF, Sandholt BV, Keller SH, Hansen AE, Clemmensen AE, Sillesen H, Hojgaard L, Ripa RS, Kjaer A. 64Cu-DOTATATE PET/MRI for Detection of Activated Macrophages in Carotid Atherosclerotic Plaques: Studies in Patients Undergoing Endarterectomy. Arterioscler Thromb Vasc Biol. 2015 Jul;35(7):1696-703. doi: 10.1161/ATVBAHA.114.305067. Epub 2015 May 14.
citation: Dubash SR, Keat N, Mapelli P, Twyman F, Carroll L, Kozlowski K, Al-Nahhas A, Saleem A, Huiban M, Janisch R, Frilling A, Sharma R, Aboagye EO. Clinical Translation of a Click-Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors. J Nucl Med. 2016 Aug;57(8):1207-13. doi: 10.2967/jnumed.115.169532. Epub 2016 May 12.