Symptomatische und systemische atherosklerotische Plaque-Aktivität bei Patienten mit peripherer arterieller Verschlusskrankheit unter Verwendung neuartiger Bildgebung (SISYPHUS)
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.
Studienübersicht
Status
Detaillierte Beschreibung
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).
Studientyp
Einschreibung (Geschätzt)
Kontakte und Standorte
Studienkontakt
- Name: Allison c Winarski, MBChB, MRCS(Ed)
- Telefonnummer: +447495905258
- E-Mail: awinarsk@ed.ac.uk
Studieren Sie die Kontaktsicherung
- Name: Rachael O Forsythe, MBChB, PhD, FRCS (Vascular)
- Telefonnummer: +44 01312423585
- E-Mail: rachael.forsythe@ed.ac.uk
Studienorte
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Midlothian
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Edinburgh, Midlothian, Vereinigtes Königreich, EH16 4SA
- Rekrutierung
- Royal Infirmary of Edinburgh
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Kontakt:
- Allison C Winarski, MBChB MRSC(Ed)
- Telefonnummer: +447495905258
- E-Mail: awinarsk@ed.ac.uk
-
Kontakt:
- Rachael O Forsythe, MBChB, PhD, FRCS (Vascular)
- Telefonnummer: 01312423585
- E-Mail: rachael.forsythe@ed.ac.uk
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Unterermittler:
- Allison C Winarski, MBChB MRCS (Ed)
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Hauptermittler:
- Rachael O Forsythe, MBChB, PhD, FRCS (Vascular)
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Unterermittler:
- David E Newby, BSc (Hons)PhD BM DM DSc FRCP
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Probenahmeverfahren
Studienpopulation
Patients will be prosectively recruited from vascular outpatient clinics and inpatient wards.
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Beobachtungsmodelle: COHORT
- Zeitperspektiven: PROSPECTIVE
Kohorten und Interventionen
Gruppe / Kohorte |
Intervention / Behandlung |
|---|---|
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Patienten mit symptomatischer peripherer arterieller Verschlusskrankheit
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Targeting vascular inflammation Targeting thrombus activity Targeting vascular microcalcification To determine anatomical and morphological atherosclerotic plaque characteristics |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in the symptomatic lower limb(s)
Zeitfenster: 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
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in remote arterial territories
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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.
Zeitfenster: 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
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Andere Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Major adverse cardiovascular events (MACE) and major adverse limb events (MALE)
Zeitfenster: 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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Mitarbeiter und Ermittler
Sponsor
Mitarbeiter
Ermittler
- Hauptermittler: Rachael O Forsythe, MBChB, PhD, FRCS (Vascular), University of Edinburgh
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Gefäßerkrankungen
- Pathologische Prozesse
- Chronische Erkrankung
- Krankheitsattribute
- Atherosklerose
- Arteriosklerose
- Arterielle Verschlusskrankheiten
- Periphere Gefäßerkrankungen
- Ischämie
- Pathologische Zustände, Anzeichen und Symptome
- Chronische, die Gliedmaßen bedrohende Ischämie
- Herz-Kreislauf-Erkrankungen
- Periphere arterielle Verschlusskrankheit
Andere Studien-ID-Nummern
- AC25008
- BHF PG/24/12097 (Andere Zuschuss-/Finanzierungsnummer: British Heart Foundation)
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