miRNAs in Critical Limb Ischemia (miRNACLI) (miRNACLI)

April 29, 2025 updated by: Fabio Martelli, IRCCS Policlinico S. Donato

Role of microRNAs in Critical Limb Ischemia

For the present study, 40 patients affected by critical limb ischemia of different severity will be enrolled: patients affected by critical limb ischemia undergoing subgenual femoropopliteal bypass; patients suffering from terminal ischemia causing gangrene and therefore undergoing major amputation of the lower limb. Biopsies from the first 20 enrolled patients will be used for miRNA profiling. The total of 40 biopsies obtained from all enrolled patients will instead be used for the validation of the miRNAs identified in the profiling.

The results obtained will be compared with those obtained in 40 control patients affected by infrarenal abdominal aortic aneurysm (AAA) undergoing endovascular exclusion surgery (EVAR) of the AAA without any ischemia of the lower limbs. Also in this case the biopsies of the first 20 control patients enrolled will be used for miRNA profiling. The total of 40 biopsies obtained from all control patients will instead be used for the validation of the miRNAs identified in the profiling. A total of 80 patients (40 cases and 40 controls) will be enrolled.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The analyzes of the expression of miRNAs and the RISC complex will be carried out on fragments of skeletal muscle taken from different sites depending on whether they are cases or controls.

Cases:

  • Patients suffering from CLI undergoing lower limb revascularization via subgenual femoropopliteal bypass: Gastrocnemius muscle biopsies will be taken.
  • Patients suffering from terminal CLI and/or gangrene of the lower limb undergoing thigh amputation: biopsies will be taken in different muscle districts. In particular, biopsies of the Sartorius or Vastus lateralis muscle will be taken at the amputation site, both from the proximal muscle belly which remains covering the bone stump, and from the part of the muscle belly sacrificed with the amputated limb. Biopsies of the Gastrocnemius and Tibialis anterior muscles will be taken from the amputated leg.
  • Patients suffering from terminal CLI and/or gangrene of the lower limb undergoing leg amputation: biopsies will be taken in different muscle districts. In particular, biopsies of the Gastrocnemius and Tibialis anterior muscles will be carried out at the amputation site, both from the proximal muscle belly which remains covering the bone stump, and from the part of the muscle belly sacrificed with the amputated limb.

Controls:

• The control subjects will be represented by individuals affected by infrarenal abdominal aortic aneurysm (AAA) free from CLI, affected and not affected by type 2 diabetes mellitus, undergoing endovascular exclusion surgery of the AAA (EVAR), similar by age and sex to CLI patients. Sartorius muscle biopsies will be taken.

The analyzes of the expression of circulating miRNAs will be carried out on 2 7 ml tubes of peripheral venous blood, taken before the surgical incision from the same cases and controls described in the previous point.

Study Type

Observational

Enrollment (Estimated)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
    • Milan
      • San Donato Milanese, Milan, Italy, 20097
        • Recruiting
        • IRCCS Policlinico San Donato
        • Sub-Investigator:
          • Giovanni Nano, MD
        • Sub-Investigator:
          • Paolo Righini, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Critical limb ischemia patients

Description

Inclusion Criteria:

Cases:

  • patients affected by CLI candidates for popliteal exploration surgery and/or subgenual femoropopliteal bypass.
  • Patients affected by CLI with irreversible ischemia and/or distal gangrene of the lower limb candidates for major amputation of the lower limb.

Controls:

• patients affected by infrarenal abdominal aortic aneurysm (AAA) undergoing endovascular exclusion surgery of the AAA (EVAR) who are free from CLI, affected and not affected by type 2 diabetes mellitus.

Exclusion Criteria:

  • Pregnant women
  • Patients carriers of genetic diseases
  • Patients suffering from malignant neoplasia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
1) Critical limb ischemia (CLI);

1)Critical limb ischemia (CLI):

  • Patients suffering from CLI undergoing lower limb revascularization via subgenual femoropopliteal bypass. muscle biopsies willbe taken.
  • Patients suffering from terminal CLI and/or gangrene of the lower limb undergoing thigh amputation. Muscle biopsies will be taken.
  • Patients suffering from terminal CLI and/or gangrene of the lower limb undergoing leg amputation. Muscle biopsies will be taken.
Diagnostic test: Critical limb ischemia: analysis of RNAs
analysis of miRNA expression levels
2)Controls
2)Controls: patients affected by infrarenal abdominal aortic aneurysm (AAA) free from CLI, affected and not affected by type 2 diabetes mellitus, undergoing endovascular exclusion surgery of the AAA (EVAR), similar by age and sex to CLI patients. Sartorius muscle biopsies will be taken.
Diagnostic test: Controls: analysis of RNAs
analysis of miRNAs expression levels

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of potentially pathogenic miRNAs in CLI and related target mRNAs.
Time Frame: 1 year to 10 years
Identify miRNAs and their targets that directly interact with the RNA Induced Silencing Complex (RISC) in muscle biopsies obtained from CLI patients.
1 year to 10 years
Identification of disease biomarkers
Time Frame: 1 year to 10 years
Identify plasma miRNAs to be used as disease biomarkers that can be used to assess disease status and severity with a minimally invasive procedure.
1 year to 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Policlinico S. Donato

Investigators

  • Principal Investigator: Fabio Martelli, IRCCS Policlinico S. Donato

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 31, 2016

Primary Completion (Estimated)

May 31, 2026

Study Completion (Estimated)

May 31, 2026

Study Registration Dates

First Submitted

September 27, 2023

First Submitted That Met QC Criteria

September 27, 2023

First Posted (Actual)

October 4, 2023

Study Record Updates

Last Update Posted (Actual)

April 30, 2025

Last Update Submitted That Met QC Criteria

April 29, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • miRNACLI

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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