Chronic Limb Threatening Ischemia, Peripheral Arterial Disease
Conditions
Keywords
Peripheral arterial disease, Chronic limb threatening ischaemia, PET-CT, cardiovascular diseases, Sodium Fluoride, GP1, DOTATATE
Brief summary
The goal of this observational study is to characterise the relationships between inflammation, microcalcification and thrombus activity in atherosclerotic plaques in peripheral and systemic vascular territories in patients with symptomatic peripheral arterial disease.
Detailed description
In peripheral arterial disease (PAD), arteries in the lower body can become narrowed and develop blockages due to a process called atherosclerosis, leading to reduced blood flow to the lower limbs. Symptoms can range from mild cramping pain in legs on walking, to loss of parts of the leg. Patients with PAD are also at a high risk of blockages in other arteries in the body that can lead to problems such as heart attacks and strokes. Despite improvements in medical treatments and surgery, the outlook for patients with PAD has not improved. Further information is required to understand the relationships between the processes that lead to narrowing and blockages (atherosclerosis) of the arteries and if they behave the same in different parts of the body. This can help to identify targeted treatments to reduce the risk of the disease getting worse and avoid heart attacks and strokes. In this study investigators plan to recruit 100 people with symptomatic PAD to undergo a series of whole body PET-CT and CT angiogram scans using different tracers targeting the processes involved in atherosclerosis. Investigators will aim to co-enrol patients taking part in the LEADER-PAD study (NCT04774159).
Interventions
RADIATIONWhole body [68Ga]DOTATATE PET-CT
Targeting vascular inflammation
RADIATIONWhole body [18F]GP1 PET-CT
Targeting thrombus activity
RADIATIONWhole body [18F]NaF PET-CT
Targeting vascular microcalcification
RADIATIONWhole body CT angiogram
To determine anatomical and morphological atherosclerotic plaque characteristics
Sponsors
University of Edinburgh
NHS Lothian
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female aged \> 18 years * Symptomatic atherosclerotic peripheral artery disease; * Intermittent claudication; with ankle/arm blood pressure ratio \<0.90 or artery stenosis \>50% in addition to at least one of the following; * \>1 vascular bed affected by atherosclerosis * Diabetes * Heart failure * Chronic kidney disease (eGFR \< 60 mL/min/1.73 m2) * Rest pain or necrosis of limb or gangrene of limb * Revascularization defined as limb bypass surgery or endovascular revascularization procedures (irrespective of the specific device used), including percutaneous transluminal angioplasty/stent of iliac or infra-inguinal arteries or extra-anatomical bypass surgery * Leg or foot amputation for arterial vascular indications * Ability to give written or verbal informed consent
Exclusion criteria
* Contraindication to colchicine or iodinated contrast * Long term requirement for colchicine for another clinical indication * Active diarrhoea * Recent lower limb revascularisation for symptomatic disease (\<6 weeks) * Renal failure (glomerular filtration rate \<30 mL/min/1.73 m2) * Cirrhosis or severe chronic liver disease * Women who are pregnant or breast-feeding * Women of child-bearing potential not protected by reliable contraception or is planning conception during the study * Current or planned long term use of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics (apart from azithromycin) * Patients deemed unlikely to return for follow up * Life expectancy \<1 year * Inability or unwilling to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in the symptomatic lower limb(s) | From baseline imaging until completion imaging at 1 year | The 3 primary endpoints will be the location and degree of: 1. inflammation: uptake of \[68Ga\]DOTATATE 2. calcification: uptake of \[18F\]NaF 3. thrombus activity: uptake of \[18F\]GP1 in peripheral arterial disease affecting the lower limbs. This will be determined by the degree of tracer standardised uptake values (SUVs) at the site of the symptomatic atherosclerotic plaque. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in remote arterial territories | From baseline imaging until completion imaging at 1 year | The secondary outcome measures will be the location and degree of inflammation, calcification and thrombus activity in remote arterial territories, including the coronary arteries, cerebral arteries, aorta and mesenteric vessels, as determined by SUVs of \[68Ga\]DOTATATE, \[18F\]NaF and \[18F\]GP1, respectively. |
| CT plaque morphology | From baseline imaging to completion imaging at 1 year | Investigators will characterise CT plaque morphology (total, calcified, non-calcified and low-attenuation plaque) in peripheral and systemic arterial beds and compare this to areas of \[68Ga\]DOTATATE, \[18F\]GP1 and \[18F\]NaF uptake. |
| The association between patient risk factors for cardiovascular disease and PET tracer uptake | Frome baseline imaging to completion imaging at 1 year | Investigators will explore the association between patient risk factors for cardiovascular disease (hypertension, diabetes, smoking) and the degree of \[68Ga\]DOTATATE, \[18F\]GP1 and \[18F\]NaF uptake as quantified by standard uptake values (SUVs). This will be measured by odds ratio (OR) with 95% confidence interval (CI) for each risk factor-tracer combination. |
| The progression of microcalcification, as defined by [18F]NaF uptake, to macrocalcification. | From baseline imaging to completion imaging at 1 year | Investigators will also aim to characterise the relationship between microcalcification progressing to calcification and the uptake of \[18F\]NaF. This will be assessed using baseline and follow-up \[18F\]NaF PET-CT SUVs and their correlation with calcified regions on CT angiography. |
Countries
United Kingdom
Contacts
CONTACTAllison c Winarski, MBChB, MRCS(Ed)
CONTACTRachael O Forsythe, MBChB, PhD, FRCS (Vascular)
PRINCIPAL_INVESTIGATORRachael O Forsythe, MBChB, PhD, FRCS (Vascular)
University of Edinburgh
Outcome results
None listed