Clinical trial NCT06066268: miRNAs in Critical Limb Ischemia (miRNACLI)
Official title: Role of microRNAs in Critical Limb Ischemia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Critical Limb Ischemia
Keywords: microRNA
Ischemia
Lead sponsor: IRCCS Policlinico S. Donato
Sponsor class: OTHER
First posted: 2023-10-04
Enrollment: 80
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Critical limb ischemia patients

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Identification of potentially pathogenic miRNAs in CLI and related target mRNAs.
timeFrame: 1 year to 10 years
measure: Identification of disease biomarkers
timeFrame: 1 year to 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: San Donato Milanese
country: Italy
facility: Irccs Policlinico San Donato
state: Milan
Study officials:
affiliation: IRCCS Policlinico S. Donato
name: Fabio Martelli
role: PRINCIPAL_INVESTIGATOR
References: