Atherosclerosis Clinical Trial
— PIILLOfficial title:
PET Imaging of Inflammation and Lipid Lowering Study
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.
Status | Recruiting |
Enrollment | 63 |
Est. completion date | March 1, 2025 |
Est. primary completion date | March 1, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 99 Years |
Eligibility | Inclusion Criteria: - 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 Criteria: - 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 |
Country | Name | City | State |
---|---|---|---|
United Kingdom | University of Cambridge | Cambridge |
Lead Sponsor | Collaborator |
---|---|
University of Cambridge | Cambridge University Hospitals NHS Foundation Trust, GE Healthcare, Lund University, Wellcome Trust |
United Kingdom,
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. — View 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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Carotid 68Ga-DOTATATE PET | Relative change from baseline in carotid artery 68Ga-DOTATATE tissue-to-blood ratio in the index vessel | 12 weeks | |
Primary | Carotid UPSA imaging | Relative change from baseline in carotid artery UPSA signal in the index vessel | 12 weeks | |
Secondary | MRI plaque burden | Relative change from baseline in carotid artery total plaque burden and lipid-rich necrotic core measured by MRI | 12 weeks | |
Secondary | Carotid 68Ga-DOTATATE vs. serum lipids | Comparison of carotid 68Ga-DOTATATE imaging to serum lipids | 12 weeks | |
Secondary | Carotid 68Ga-DOTATATE vs. hsCRP | Comparison of carotid 68Ga-DOTATATE imaging to high-sensitivity C-reactive protein (hsCRP) | 12 weeks |
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