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
- Are there results?
- Not yet: the study is under way
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
Show all 11Show fewer
- 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
Show all 12Show fewer
- 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.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- 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
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Symptomatic and Systemic Atherosclerotic Plaque Activity in Patients With Peripheral Arterial Disease Using Novel Imaging
- ClinicalTrials.gov ID
- NCT07472049
- Acronym / sponsor ID
- SISYPHUS / AC25008
- Keywords
- Peripheral arterial disease, Chronic limb threatening ischaemia, PET-CT, cardiovascular diseases, Sodium Fluoride, GP1, DOTATATE
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian
- Study start
- 31 Jul 2025 (actual)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Jul 2029 (estimated)
- First posted
- 16 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with symptomatic peripheral arterial disease | – | 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients will be prosectively recruited from vascular outpatient clinics and inpatient wards.
Key inclusion criteria (11 listed)
- Male or female aged > 18 years
- Symptomatic atherosclerotic peripheral artery disease;
- Ability to give written or verbal informed consent
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Whole body [68Ga]DOTATATE PET-CTTargeting vascular inflammation | Radiation | Patients with symptomatic peripheral arterial disease |
| Whole body [18F]GP1 PET-CTTargeting thrombus activity | Radiation | Patients with symptomatic peripheral arterial disease |
| Whole body [18F]NaF PET-CTTargeting vascular microcalcification | Radiation | Patients with symptomatic peripheral arterial disease |
| Whole body CT angiogramTo determine anatomical and morphological atherosclerotic plaque characteristics | Radiation | Patients with symptomatic peripheral arterial disease |
Primary outcome
Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in the symptomatic lower limb(s)
Time frame: 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.
4 secondary outcomes
Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in remote arterial territories
Time frame: From baseline imaging until completion imaging at 1 year
CT plaque morphology
Time frame: From baseline imaging to completion imaging at 1 year
The association between patient risk factors for cardiovascular disease and PET tracer uptake
Time frame: Frome baseline imaging to completion imaging at 1 year
The progression of microcalcification, as defined by [18F]NaF uptake, to macrocalcification.
Time frame: From baseline imaging to completion imaging at 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2026.
- Individual participant dataSharing planned: No
Related trials for Peripheral Arterial Disease
Active, not recruiting
SUCCESS (SelUtion, Safety, effiCaCy, hEalth economicS and promS) PTA Study
Peripheral Artery Disease
RecruitingPhase 3
Reducing Adverse Vascular Outcomes With Factor XI Inhibition in Adult Participants With Peripheral Artery Disease
Peripheral Artery Disease (PAD)
Recruiting
The THOR IDE Study
Peripheral Artery Disease, Peripheral Artery Stenosis
Not yet recruiting
Daily Stretching to Improve Walking in Older Patients With Peripheral Artery Disease: The STRETCH PAD Study
Peripheral Artery Disease (PAD), Intermittent Claudication
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rachael O Forsythe, MBChB, PhD, FRCS (Vascular) principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Peripheral Arterial Disease and Chronic Limb Threatening Ischemia, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Allison c Winarski, MBChB, MRCS(Ed) (+447495905258, awinarsk@ed.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantification of PET tracer uptake of [68Ga]DOTATATE, [18F]GP1 and [18F]NaF in the symptomatic lower limb(s) (time frame: From baseline imaging until completion imaging at 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.