Peripheral Arterial DiseaseSISYPHUSNCT07472049
Symptomatic and Systemic Atherosclerotic Plaque Activity in Patients With Peripheral Arterial Disease Using Novel Imaging
An observational study of Peripheral Arterial Disease and Chronic Limb Threatening Ischemia, run by University of Edinburgh at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peripheral Arterial Disease, Chronic Limb Threatening Ischemia
- What is being tested?
- Whole body [68Ga]DOTATATE PET-CT, Whole body [18F]GP1 PET-CT and Whole body [18F]NaF PET-CT
- Type of treatment
- Surgery or procedure
- How many people
- 100 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 31 Jul 2025to Jul 2029
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients will be prosectively recruited from vascular outpatient clinics and inpatient wards.
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Infirmary of Edinburgh
Edinburgh, Midlothian, EH16 4SA
Allison C Winarski, MBChB MRSC(Ed), +447495905258, awinarsk@ed.ac.uk
Rachael O Forsythe, MBChB, PhD, FRCS (Vascular), 01312423585, rachael.forsythe@ed.ac.uk
About this study
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.
Read the 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).
- Being tested
- Whole body [68Ga]DOTATATE PET-CT, Whole body [18F]GP1 PET-CT, Whole body [18F]NaF PET-CT, Whole body CT angiogram
- Keywords
- Peripheral arterial disease, Chronic limb threatening ischaemia, PET-CT, cardiovascular diseases, Sodium Fluoride, GP1, DOTATATE
- Medical subject headings
- Peripheral Arterial Disease, Chronic Limb-Threatening Ischemia, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Whole body [68Ga]DOTATATE PET-CTRadiation
Targeting vascular inflammation
Whole body [18F]GP1 PET-CTRadiation
Targeting thrombus activity
Whole body [18F]NaF PET-CTRadiation
Targeting vascular microcalcification
Whole body CT angiogramRadiation
To determine anatomical and morphological atherosclerotic plaque characteristics
| Study group | Role | What they receive |
|---|---|---|
| Patients with symptomatic peripheral arterial disease | Not described Receives: Radiation: Whole body [68Ga]DOTATATE PET-CT; Radiation: Whole body [18F]GP1 PET-CT; Radiation: Whole body [18F]NaF PET-CT; Radiation: Whole body CT angiogram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in the symptomatic lower limb(s)
The 3 primary endpoints will be the location and degree of:
- inflammation: uptake of [68Ga]DOTATATE
- calcification: uptake of [18F]NaF
- 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.
Measured: From baseline imaging until completion imaging at 1 year
Secondary outcomes (4)
Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in remote arterial territories
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.
Measured: From baseline imaging until completion imaging at 1 year
CT plaque morphology
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.
Measured: From baseline imaging to completion imaging at 1 year
The association between patient risk factors for cardiovascular disease and PET tracer uptake
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.
Measured: Frome baseline imaging to completion imaging at 1 year
The progression of microcalcification, as defined by [18F]NaF uptake, to macrocalcification.
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.
Measured: From baseline imaging to completion imaging at 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2026
- Study start31 Jul 2025
- Primary completionJul 2028 (estimated)
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian
- Responsible party
- Sponsor
- Investigators
- Rachael O Forsythe, MBChB, PhD, FRCS (Vascular), Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07472049
- Sponsor's protocol ID
- AC25008
- Other IDs
- BHF PG/24/12097
- Acronym
- SISYPHUS
- Status last verified
- Sep 2026
- First submitted
- 15 Sep 2025
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No