Activité symptomatique et systémique de la plaque d'athérosclérose chez les patients atteints de maladie artérielle périphérique utilisant une imagerie innovante (SISYPHUS)
Activité symptomatique et systémique de la plaque athéroscléreuse chez les patients atteints de maladie artérielle périphérique utilisant une imagerie innovante
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.
Aperçu de l'étude
Statut
Description détaillée
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).
Type d'étude
Inscription (Estimé)
Contacts et emplacements
Coordonnées de l'étude
- Nom: Allison c Winarski, MBChB, MRCS(Ed)
- Numéro de téléphone: +447495905258
- E-mail: awinarsk@ed.ac.uk
Sauvegarde des contacts de l'étude
- Nom: Rachael O Forsythe, MBChB, PhD, FRCS (Vascular)
- Numéro de téléphone: +44 01312423585
- E-mail: rachael.forsythe@ed.ac.uk
Lieux d'étude
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Midlothian
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Edinburgh, Midlothian, Royaume-Uni, EH16 4SA
- Recrutement
- Royal Infirmary of Edinburgh
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Contact:
- Allison C Winarski, MBChB MRSC(Ed)
- Numéro de téléphone: +447495905258
- E-mail: awinarsk@ed.ac.uk
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Contact:
- Rachael O Forsythe, MBChB, PhD, FRCS (Vascular)
- Numéro de téléphone: 01312423585
- E-mail: rachael.forsythe@ed.ac.uk
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Sous-enquêteur:
- Allison C Winarski, MBChB MRCS (Ed)
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Chercheur principal:
- Rachael O Forsythe, MBChB, PhD, FRCS (Vascular)
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Sous-enquêteur:
- David E Newby, BSc (Hons)PhD BM DM DSc FRCP
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
Méthode d'échantillonnage
Population étudiée
Patients will be prosectively recruited from vascular outpatient clinics and inpatient wards.
La description
Inclusion Criteria:
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Male or female aged > 18 years
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Symptomatic atherosclerotic peripheral artery disease;
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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)
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Rest pain or necrosis of limb or gangrene of limb
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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
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Leg or foot amputation for arterial vascular indications
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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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Modèles d'observation: COHORT
- Perspectives temporelles: PROSPECTIVE
Cohortes et interventions
Groupe / Cohorte |
Intervention / Traitement |
|---|---|
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Patients atteints de maladie artérielle périphérique symptomatique
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Targeting vascular inflammation Targeting thrombus activity Targeting vascular microcalcification To determine anatomical and morphological atherosclerotic plaque characteristics |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in the symptomatic lower limb(s)
Délai: From baseline imaging until completion imaging at 1 year
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The 3 primary endpoints will be the location and degree of:
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From baseline imaging until completion imaging at 1 year
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in remote arterial territories
Délai: From baseline imaging until completion imaging at 1 year
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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. |
From baseline imaging until completion imaging at 1 year
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CT plaque morphology
Délai: From baseline imaging to completion imaging at 1 year
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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. |
From baseline imaging to completion imaging at 1 year
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The association between patient risk factors for cardiovascular disease and PET tracer uptake
Délai: Frome baseline imaging to completion imaging at 1 year
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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. |
Frome baseline imaging to completion imaging at 1 year
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The progression of microcalcification, as defined by [18F]NaF uptake, to macrocalcification.
Délai: From baseline imaging to completion imaging at 1 year
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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. |
From baseline imaging to completion imaging at 1 year
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Major adverse cardiovascular events (MACE) and major adverse limb events (MALE)
Délai: From baseline imaging to completion imaging at 1 year
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Exploratory endpoints will include major adverse cardiovascular events (acute myocardial infarction, stroke or cardiovascular death) and major adverse limb events (revascularisation or lower limb amputation) as well as death from any cause. |
From baseline imaging to completion imaging at 1 year
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Rachael O Forsythe, MBChB, PhD, FRCS (Vascular), University of Edinburgh
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies vasculaires
- Processus pathologiques
- Maladie chronique
- Attributs de la maladie
- Athérosclérose
- Artériosclérose
- Maladies artérielles occlusives
- Maladies vasculaires périphériques
- Ischémie
- Conditions pathologiques, signes et symptômes
- Ischémie chronique menaçant les membres
- Maladies cardiovasculaires
- Maladie artérielle périphérique
Autres numéros d'identification d'étude
- AC25008
- BHF PG/24/12097 (Autre subvention/numéro de financement: British Heart Foundation)
Plan pour les données individuelles des participants (IPD)
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Informations sur les médicaments et les dispositifs, documents d'étude
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