Utility of Sortilin as a Biomarker of Restenosis After Lower Extremity Endovascular Revascularization

Utility of Sortilin as a Biomarker of Restenosis After Lower Extremity Endovascular Revascularization in a Cohort of Diabetic Patients With Peripheral Artery Disease and Chronic Limb-threatening Ischemia

Sortilin is a 95-kDa protein related to circulating cholesterol. It is found inside different cell types and circulating in blood and it has been associated with the risk of atherosclerosis development and cardiovascular diseases.

The goal of this observational study is to evaluate the potential use of circulating sortilin as a biomarker of vascular adverse outcomes in patients with peripheral artery disease (PAD) and chronic limb-threatening ischemia (CLTI) requiring a procedure of endovascular revascularization.

The main questions it aims to answer are:

• association between sortilin serum levels and risk of restenosis after lower extremity revascularization.
• association between sortilin serum levels and acute limb ischemia, major vascular amputations, and limb-threatening ischemia needing for urgent revascularization after lower extremity revascularization.

Patients with PAD and CLTI requiring lower extremity endovascular revascularization will undergo blood sampling for the dosage of circulating sortilin before the endovascular procedure.

Incidence of restenosis and acute limb ischemia, major vascular amputations, and limb-threatening ischemia needing for urgent revascularization will be collected in a 12-months follow-up and will be associated with sortilin serum levels at baseline.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Artery Disease

• Study Type: Observational
• Enrollment (Anticipated): 207

Contacts and Locations

• Study Contact: Name: Andrea Flex, MD, PhD; Phone Number: +39 06 3015 4293; Email: andrea.flex@policlinicogemelli.it

Study Locations

• Italy
  • Rome, Italy
    • Recruiting
    • Fondazione Policlinico Universitario A. Gemelli IRCCS
    • Contact: Andrea Flex, MD, PhD; Phone Number: +39 06 3015 4293; Email: andrea.flex@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

We will enroll consecutive statin-naïve subjects with type 2 diabetes mellitus with PAD requiring for endovascular revascularization and admitted to Internal Medicine Cardiovascular Unit of the Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma.

Description

Inclusion Criteria:

• type 2 diabetes mellitus diagnosis;
• Ankle/Brachial Index (ABI) of less than 80;
• at least one lower limb stenosis greater than 50% documented by Ultrasound Color Doppler (US);
• stage 4 or 5 PAD diagnosis according to the Rutherford classification;
• presence of chronic limb threatening ischemia;
• indication for LER of the target arterial stenosis.

Exclusion Criteria:

• statin therapy within the previous 3 months;
• revascularization of the lower limb in the previous 3 months;
• diabetic foot ulcers with signs of active infection or osteomyelitis;
• diabetic peripheral neuropathy;
• homozygous familial hypercholesterolemia;
• absolute contraindication to antiplatelet therapy;
• thrombophilia;
• active cancer;
• active autoimmune disease;
• liver disease at functional status B or C according to Child-Pugh.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between sortilin serum levels before endovascular revascularization and incidence of restenosis	To evaluate the association between sortilin serum levels before endovascular revascularization and restenosis during the follow-up period.	12-months follow-up
Correlation between sortilin serum levels before endovascular revascularization and incidence of acute limb ischemia	To evaluate the association between sortilin serum levels before endovascular revascularization and acute limb ischemia during the follow-up period.	12-months follow-up
Correlation between sortilin serum levels before endovascular revascularization and incidence of amputations	To evaluate the association between sortilin serum levels before endovascular revascularization and amputations during the follow-up period.	12-months follow-up
Correlation between sortilin serum levels before endovascular revascularization and chronic limb-threatening ischemia needing for urgent revascularization	To evaluate the association between sortilin serum levels before endovascular revascularization and limb-threatening ischemia needing for urgent revascularization during the follow-up period.	12-months follow-up

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Andrea Flex, MD, PhD, Fondazione Policlinico Universitario A. gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2019
• Primary Completion (Anticipated): October 31, 2024
• Study Completion (Anticipated): October 31, 2024

Study Registration Dates

• First Submitted: February 24, 2023
• First Submitted That Met QC Criteria: February 25, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Peripheral Artery Disease; Restenosis; Amputation; Acute limb ischemia; Sortilin; Limb-threatening ischemia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Vascular Diseases; Peripheral Arterial Disease
• Other Study ID Numbers: 1990 (CTEP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No