Clinical trial NCT05757297: Gut Microbiota in Patients With Peripheral Arterial Disease and Chronic Limb-threatening Ischemia
Official title: Gut Microbiota and Failure of Endovascular Revascularization in Diabetic Patients With Peripheral Arterial Disease and Chronic Limb-threatening Ischemia
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Peripheral Arterial Disease
Keywords: microbiota
gut microbiota
TMAO
MACE
MALE
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2023-03-07
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: We will enroll consecutive subjects with PAD and CLTI requiring for endovascular revascularization and admitted to Internal Medicine Cardiovascular Unit of the Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma.

Brief summary: Microbiota has been associated with risk factors for cardiovascular diseases (hypertension, obesity, dyslipidemia, diabetes mellitus, heart failure). In animal models, the gut microbiota produces pro-inflammatory proteoglycans that increase the extent of myocardial infarction, reduced by treatment with probiotics (Lactobacillus). TMAO, a blood metabolite directly dependent on the gut microbiota is related to atherosclerotic plaque instability and major adverse cardiovascular events (MACE) in humans. Recent data demonstrate that blood levels of TMAO directly correlate with the risk of major MACE and mortality in patients with peripheral arterial disease (PAD).

The goal of this observational study is to evaluate the association between gut microbiota and TMAO serum levels and MACE and major adverse limb events (MALE) in patients with PAD and chronic limb threatening ischemia (CLTI) requiring a procedure of endovascular revascularization.

The main questions it aims to answer are:

* association between gut microbiota and TMAO serum levels and MALE after lower extremity revascularization.
* association between gut microbiota and TMAO serum levels and MACE after lower extremity revascularization.

Patients with CLTI requiring lower extremity endovascular revascularization will undergo stool sampling for determination of gut microbiota and blood sampling for the dosage of circulating TMAO before the endovascular procedure.

Incidence of MALE and MACE will be collected in a 24-months follow-up and will be associated with gut microbiota and TMAO serum levels.


Eligibility criteria: Inclusion Criteria:

* age of at least 18 years
* 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:

* acute infections at present or in the previous month
* antibiotic treatment in the previous month
* primary hyperparathyroidism
* revascularization of the lower limb in the previous 3 months
* diabetic foot ulcers with signs of active infection or osteomyelitis
* organ transplantation
* active cancer
* liver disease at functional status B or C according to Child-Pugh
* absolute contraindication to antiplatelet therapy
* thrombophilia
* contraindication to endovascular revascularization

Primary outcomes:
measure: Association between incidence of MALE and gut microbiota and TMAO serum levels
timeFrame: 24-months follow-up
Secondary outcomes:
measure: Association between incidence of myocardial infarction and gut microbiota and TMAO serum levels
timeFrame: 24-months follow-up
measure: Association between incidence of stroke and gut microbiota and TMAO serum levels
timeFrame: 24-months follow-up
measure: Association between incidence of cardiovascular death and gut microbiota and TMAO serum levels
timeFrame: 24-months follow-up
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS
Study officials:
References: