Clinical trial NCT05813171: The Effects of Allicor on Patients After Revascularization Treatment During a Year
Official title: The Effects of Dietary Supplementation Allicor on Patients With Multifocal Atherosclerosis After Peripheral Artery Revascularization Treatment During a Year
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Atherosclerosis
Peripheral Arterial Disease
Keywords: atherosclerosis
inflammation
DNA, Mitochondrial
Lead sponsor: Institute for Atherosclerosis Research, Russia
Sponsor class: OTHER
First posted: 2023-04-14
Enrollment: 300
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized controlled trial with two parallel groups of participants
Primary purpose: TREATMENT

Brief summary: A significant challenge in medical care is atherosclerotic occlusion of peripheral arteries, such as lower extremities and brachiocephalic arteries, which can eventually lead to loss of limbs or fatal ischemic strokes. Revascularizing surgical interventions can restore the lumen of the arteries and provide an effective way to treat such patients. However, up to a third of patients need re-intervention or experience cardiovascular complications within a year after surgery. The purpose of this study is to evaluate the effect of adding the natural dietary supplement Allicor to conventional treatment on the incidence of cardiovascular complications and treatment effectiveness 12 months after revascularization. Another valuable area of investigation is the search for predictors of long-term cardiovascular complications after revascularization, which could be markers of inflammation and heteroplasmy levels in the patient's mitochondrial genome.

Detailed description: Recently, atherosclerosis of large arteries has become a common problem affecting the quality of life and life expectancy of the population. In addition to atherosclerosis of coronary arteries leading to myocardial ischemia, another significant issue is atherosclerosis of the lower limb and brachiocephalic arteries. Typically, arteries are affected in multiple areas, resulting in multifocal atherosclerosis of several arterial basins. Consequently, 14 to 19% of patients suffering from damage to the arteries of the lower extremities have significant stenosis of the common carotid arteries. Clinical guidelines from the European Society of Cardiology (ESC) and the European Society for Vascular Surgery (ESVS) emphasize the need to examine other arteries in patients with atherosclerosis of the arteries of the lower extremities. Clinical screening for carotid and subclavian artery stenosis is also recommended.

The surgical method for treating arterial occlusive lesions includes revascularization interventions to restore blood flow, thus eliminating tissue ischemia and preventing fatal and disabling consequences. In addition to surgical treatment, medications that lower blood cholesterol and reduce blood thrombogenesis are used.

An important predictor of disease and treatment efficiency is the level of systemic inflammatory markers, such as protein-C. An anti-inflammatory approach is not used for treating patients with multifocal atherosclerosis. However, investigating new markers of inflammation may be promising for the development of new diagnostics.

Insofar as up to a third of patients face the need for re-intervention or suffer cardiovascular complications within a year after revascularization surgery, the search for new approaches to treat multifocal arterial atherosclerosis is necessary.

Long-term use of drugs of natural origin with anti-inflammatory and anti-atherosclerotic effects may be promising.

Dietary Supplementation Allicor consists of dried garlic. There is a trial study (ClinicalTrials.gov Identifier: NCT01734707) that determined the ability of Allicor to have a beneficial effect on patients with atherosclerosis, and there are also data on the beneficial effect of Allicor on the condition of patients with coronary heart disease. Another randomized, double-blind, placebo-controlled trial of a dietary supplement made of garlic (ClinicalTrials.gov Identifier: NCT03860350) found benefits for patients with coronary artery atherosclerosis. Thus, there is reason to believe that Allicor will improve treatment outcomes in patients with multifocal atherosclerosis.

The aim of this study is to investigate how the addition of Allicor to the standard treatment affects the incidence of serious cardiovascular events during a year after revascularization intervention. Also to be assessed is the need for repeated operations, as well as an evaluation of arterial flow and arterial wall. The study will also assess promising markers related to atherosclerosis and inflammation - an in vitro monocyte cytokine release test, and heteroplasmy levels of the patient's mitochondrial genome variants associated with atherosclerosis.

Eligibility criteria: Inclusion Criteria:

1. Age \>40 and \<75 years
2. A revascularization (including stenting, endarterectomy, artery prosthetic or bypass grafting) is indicated for the patient because of chronic atherosclerotic obliteration of the arteries of the lower extremities and/or common carotid arteries.
3. Patients passed a complex of instrumental and laboratory examinations before revascularization, including X-ray contrast angiography or ultrasound examination of common carotid arteries and arteries of the lower extremities, the ankle-brachial index (ABI) assessment, biochemical analysis of blood included assessment of cholesterol, triglycerides, low density lipoproteins, high density lipoproteins and glucose levels.
4. The possibility of monitoring the patient for 12 months after revascularization, including phone contacts and visits to the clinic after 6 and 12 months.
5. Patient or legal authorized representative capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

1. Repeated revascularization surgery.
2. Trophic ulcers of the lower extremities.
3. Critical and urgent cardiovascular conditions: tissue ischemia stage III-IV, stroke, acute coronary syndrome, myocardial infarction, chronic heart failure III and IV class NYHA (New York Heart Association).
4. Other critical and urgent conditions not associated with cardiovascular diseases, including the need for urgent interventions, chronic renal failure stages IV-V (creatinine clearance \< 30 ml / min according to the Cockcroft-Gault Equation)
5. High degree of disability of the patient (4 or higher points on the modified Rankin scale).
6. History of systemic autoimmune diseases.
7. Significant weight loss (\> 10% of body weight in the previous year) of unknown etiology.
8. Conditions that limit adherence to participation in the study (dementia, neuropsychiatric diseases, drug addiction, alcoholism, etc.).
9. Participation in other clinical studies (or use of investigational substances) within 3 months prior to study entry.
10. Patients with malignant tumors, including the postoperative period with chemotherapy and/or radiation therapy.
11. Carriers of HIV or viral hepatitis
12. Pregnancy or breast feeding
13. Refusal to participate in the study.

Primary outcomes:
measure: Frequency of fatal cardiovascular events
timeFrame: Evaluated in 12 months from revascularization interventions
measure: Frequency of clinically significant cardiovascular events
timeFrame: Evaluated in 12 months from revascularization interventions
measure: Frequency of indications for a second revascularization
timeFrame: Evaluated in 12 months from revascularization interventions
Secondary outcomes:
measure: Change in the degree of stenosis of the peripheral arteries (lower limbs arteries, common carotid arteries)
timeFrame: Evaluated in 6 and in 12 months from revascularization interventions
measure: Variation of intima-media thickness of common carotid arteries
timeFrame: Evaluated in 6 and in 12 months from revascularization interventions
measure: The maximal walking distance (MWD)
timeFrame: Evaluated in 6 and in 12 months from revascularization interventions
measure: Change in the ankle-brachial index (ABI)
timeFrame: Evaluated in 6 and in 12 months from revascularization interventions.
measure: Change in the level of cytokine response of monocytes after double stimulation with lipopolysaccharide in in vitro cell culture
timeFrame: Evaluated in 6 and in 12 months from revascularization interventions
measure: Changes in the percentage of heteroplasmy of the mitochondrial genome of blood leukocytes in variants associated with atherosclerosis
timeFrame: Evaluated in 6 and in 12 months from revascularization interventions.
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Institute for Atherosclerosis Research
Study officials:
affiliation: "Russian research center of surgery named after academician B.V. Petrovsky"
name: Nikolay K Shakhpazyan, PhD; Dr.
role: PRINCIPAL_INVESTIGATOR
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