Symptomatische en Systemische Atherosclerotische Plaque Activiteit bij Patiënten met Perifeer Arterieel Vaatlijden met Behulp van Nieuwe Beeldvorming (SISYPHUS)
Symptomatische en Systemische Atherosclerotische Plaque Activiteit bij Patiënten met Perifeer Arterieel Vaatlijden met Gebruik van Nieuwe Beeldvorming
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.
Studie Overzicht
Toestand
Gedetailleerde beschrijving
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).
Studietype
Inschrijving (Geschat)
Contacten en locaties
Studiecontact
- Naam: Allison c Winarski, MBChB, MRCS(Ed)
- Telefoonnummer: +447495905258
- E-mail: awinarsk@ed.ac.uk
Studie Contact Back-up
- Naam: Rachael O Forsythe, MBChB, PhD, FRCS (Vascular)
- Telefoonnummer: +44 01312423585
- E-mail: rachael.forsythe@ed.ac.uk
Studie Locaties
-
-
Midlothian
-
Edinburgh, Midlothian, Verenigd Koninkrijk, EH16 4SA
- Werving
- Royal Infirmary of Edinburgh
-
Contact:
- Allison C Winarski, MBChB MRSC(Ed)
- Telefoonnummer: +447495905258
- E-mail: awinarsk@ed.ac.uk
-
Contact:
- Rachael O Forsythe, MBChB, PhD, FRCS (Vascular)
- Telefoonnummer: 01312423585
- E-mail: rachael.forsythe@ed.ac.uk
-
Onderonderzoeker:
- Allison C Winarski, MBChB MRCS (Ed)
-
Hoofdonderzoeker:
- Rachael O Forsythe, MBChB, PhD, FRCS (Vascular)
-
Onderonderzoeker:
- David E Newby, BSc (Hons)PhD BM DM DSc FRCP
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Bemonsteringsmethode
Studie Bevolking
Patients will be prosectively recruited from vascular outpatient clinics and inpatient wards.
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Observatiemodellen: COHORT
- Tijdsperspectieven: PROSPECTIVE
Cohorten en interventies
Groep / Cohort |
Interventie / Behandeling |
|---|---|
|
Patiënten met symptomatische perifere arteriële ziekte
|
Targeting vascular inflammation Targeting thrombus activity Targeting vascular microcalcification To determine anatomical and morphological atherosclerotic plaque characteristics |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in the symptomatic lower limb(s)
Tijdsspanne: From baseline imaging until completion imaging at 1 year
|
The 3 primary endpoints will be the location and degree of:
|
From baseline imaging until completion imaging at 1 year
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in remote arterial territories
Tijdsspanne: 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. |
From baseline imaging until completion imaging at 1 year
|
|
CT plaque morphology
Tijdsspanne: 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. |
From baseline imaging to completion imaging at 1 year
|
|
The association between patient risk factors for cardiovascular disease and PET tracer uptake
Tijdsspanne: 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. |
Frome baseline imaging to completion imaging at 1 year
|
|
The progression of microcalcification, as defined by [18F]NaF uptake, to macrocalcification.
Tijdsspanne: 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. |
From baseline imaging to completion imaging at 1 year
|
Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Major adverse cardiovascular events (MACE) and major adverse limb events (MALE)
Tijdsspanne: From baseline imaging to completion imaging at 1 year
|
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
|
Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Rachael O Forsythe, MBChB, PhD, FRCS (Vascular), University of Edinburgh
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Vaatziekten
- Pathologische processen
- Chronische ziekte
- Ziekte attributen
- Atherosclerose
- Arteriosclerose
- Arteriële occlusieve ziekten
- Perifere vaataandoeningen
- Ischemie
- Pathologische aandoeningen, tekenen en symptomen
- Chronische ledemaatbedreigende ischemie
- Hart-en vaatziekten
- Perifere arteriële ziekte
Andere studie-ID-nummers
- AC25008
- BHF PG/24/12097 (Ander subsidie-/financieringsnummer: British Heart Foundation)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .