NCT04073797

PET Imaging of Inflammation and Lipid Lowering Study

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 63 (estimated)
• Sponsor: University of Cambridge · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

While 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging has been used as an early marker of drug efficacy in numerous clinical cardiovascular drug trials, as a glucose analog, its signal in the vasculature lacks inflammatory cell-specificity. Moreover, high background 18F-FDG signals from the myocardium often preclude coronary artery imaging, despite attempts to suppress myocardial tracer uptake by dietary manipulation. These limitations of 18F-FDG for measuring changes in vascular inflammation arising from drug intervention highlight important unmet 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 68Ga-DOTATATE can quantify drug-induced changes in arterial inflammation, patients with primary hypercholesterolaemia (non-familial or familial) or mixed dyslipidaemia with stable cardiovascular Disease (CVD) and elevated LDL cholesterol ≥2.6 despite maximum tolerated statins with or without other lipid lowering therapies will undergo carotid artery 68Ga-DOTATATE PET-magnetic resonance imaging (MRI) in a randomised, double-blind, placebo-controlled study of inclisiran or colchicine. In parallel, we will examine a novel method for detecting plaque composition based on analysis of ultrasound centre frequency shifts, which was developed by collaborators in Lund University, Sweden. The Ultrasound Plaque Structure Analysis (UPSA) method uses radiofrequency algorithms to create real-time tissue-like maps of carotid plaques. Participants in the study will undergo carotid ultrasound imaging using the UPSA method in addition to PET/MRI.

Conditions

• Hypercholesterolemia
• Hypercholesterolemia, Familial
• Atherosclerosis
• Carotid Artery Plaque

Interventions

Type	Name	Description
DRUG	Inclisiran	Inclisiran 284 mg, one injection
DIAGNOSTIC_TEST	68Ga-DOTATATE PET-MRI	68Ga-DOTATATE PET-MRI at baseline and 12 weeks
DRUG	Colchicine	Colchicine 500 mcg tablet once daily

Timeline

• Start date: 2023-03-20
• Primary completion: 2025-10-01
• Completion: 2026-03-01
• First posted: 2019-08-29
• Last updated: 2024-07-19

Locations

1 site across 1 country: United Kingdom