PET Imaging of Inflammation and Lipid Lowering Study
University of Cambridge
63 participants
Mar 20, 2023
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria6
- Male or female participants \>18 years old
- Able to give written, informed consent and to lie flat
- Have primary hypercholesterolaemia (non-familial or definite or possible heterozygous familial hypercholesterolaemia (HeFH) based on clinical criteria) or mixed dyslipidaemia, and
- History of CVD (acute coronary syndrome, coronary or other revascularisation procedures, coronary heart disease, ischaemic stroke, or peripheral arterial disease) and elevated LDL cholesterol ≥2.6 despite maximum tolerated statins with or without other lipid lowering therapies (see NICE TA 733), and
- Lipid lowering therapy unchanged for at least 6 weeks prior to screening, and
- Pre-existing carotid atherosclerotic plaque ≥15mm by B-mode ultrasound
Exclusion Criteria14
- Women of childbearing potential not using adequate contraception
- Contra-indication to MRI scanning
- Statin-associated myositis or liver function abnormality
- Already taking inclisiran or colchicine
- Sensitivity and/or contraindication to inclisiran or colchicine. Contraindications to colchicine include severe hepatic or renal impairment, blood disorders, and patients with renal or hepatic impairment who are taking a P-gp inhibitor or a strong CYP3A4 inhibitor
- Contrast allergy or contrast-nephropathy
- Chronic kidney disease (eGFR \<30 mL/min/1.73 m2)
- Cardiovascular event within 6 months
- Any medical condition, in the opinion of the investigator, that prevents the participant from lying flat during scanning, or from participating in the study
- Uncontrolled chronic inflammatory disorder
- History of recent malignancy deemed relevant to the study by the investigator
- Treatment with medications that result in significant drug to drug interactions with the study medications
- Current use of systemic corticosteroids or other immunosuppressive drugs
- Previous or planned carotid endarterectomy surgery or stenting on the index side
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Interventions
Inclisiran 284 mg, one injection
68Ga-DOTATATE PET-MRI at baseline and 12 weeks
Colchicine 500 mcg tablet once daily
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT04073797