The Effects of Allicor on Patients After Revascularization Treatment During a Year

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effects of Dietary Supplementation Allicor on Patients With Multifocal Atherosclerosis After Peripheral Artery Revascularization Treatment During a Year

Conditions
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Atherosclerosis, Peripheral Arterial Disease

Intervention / Treatment
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* Dietary Supplement: Allicor
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >40 and <75 years 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. 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. The possibility of monitoring the patient for 12 months after revascularization, including phone contacts and visits to the clinic after 6 and 12 months. 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: Repeated revascularization surgery. Trophic ulcers of the lower extremities. 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). 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) High degree of disability of the patient (4 or higher points on the modified Rankin scale). History of systemic autoimmune diseases. Significant weight loss (> 10% of body weight in the previous year) of unknown etiology. Conditions that limit adherence to participation in the study (dementia, neuropsychiatric diseases, drug addiction, alcoholism, etc.). Participation in other clinical studies (or use of investigational substances) within 3 months prior to study entry. Patients with malignant tumors, including the postoperative period with chemotherapy and/or radiation therapy. Carriers of HIV or viral hepatitis Pregnancy or breast feeding Refusal to participate in the study.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized controlled trial with two parallel groups of participants
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental: Allicor<br>Dietary Supplement: Allicor 150 mg capsule by mouth two times a day during the year | Dietary Supplement: Allicor<br>* Participants will take Allicor capsules in addition to standard treatment for a year.<br>* Other names: 150 mg capsules of dried dried garlic powder;|
| Placebo Comparator: Placebo<br>Placebo capsule manufactured to mimic Allicor 150 mg capsule by mouth two times a day during the year | Drug: Placebo<br>* Participants will take the placebo capsules in addition to standard treatment for a year.<br>* Other names: 150 mg inert capsules mimic capsules Allicor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of fatal cardiovascular events | Fatal cardiovascular events include: death from myocardial infarction, other forms of coronary heart disease (CHD), stroke, including sudden death and death within 24 hours of symptom onset, death from other non-coronary cardiovascular diseases except definitely non-atherosclerotic causes of death. | Evaluated in 12 months from revascularization interventions | 
| Frequency of clinically significant cardiovascular events | Clinically significant cardiovascular events include: acute myocardial infarction and acute coronary syndrome, acute cerebrovascular accident, progressive heart failure, hospitalization due to critical limb ischemia. | Evaluated in 12 months from revascularization interventions | 
| Frequency of indications for a second revascularization | Frequency of second revascularization events during the year. | Evaluated in 12 months from revascularization interventions | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the degree of stenosis of the peripheral arteries (lower limbs arteries, common carotid arteries) | According to angiography or ultrasonography examination | Evaluated in 6 and in 12 months from revascularization interventions | 
| Variation of intima-media thickness of common carotid arteries | Variation of intima-media thickness of common carotid arteries measured with B-mode ultrasound of carotid arteria. | Evaluated in 6 and in 12 months from revascularization interventions | 
| The maximal walking distance (MWD) | Measuring the maximal walking distance (MWD) with treadmill exercise testing | Evaluated in 6 and in 12 months from revascularization interventions | 
| Change in the ankle-brachial index (ABI) | Determination of the ratio systolic blood pressure within the brachial arteries and systolic blood pressure within the ankle arteries. | Evaluated in 6 and in 12 months from revascularization interventions. | 
| Change in the level of cytokine response of monocytes after double stimulation with lipopolysaccharide in in vitro cell culture | Cytokine level measurement by ELISA (TNF-a; IL-1b; IL-6; IL-8; IL-10; CCL2) after the first and second LPS stimulation of monocytes. | Evaluated in 6 and in 12 months from revascularization interventions | 
| Changes in the percentage of heteroplasmy of the mitochondrial genome of blood leukocytes in variants associated with atherosclerosis | Includes variants m.12315G>A, m.13513G>A, m.14459G>A, m.14846G>A, m.15059G>A, m.1555A>G, m.3256C>T, m.3336T>C, m.5178C>A, m.652delG measured with quantitative PCR. | Evaluated in 6 and in 12 months from revascularization interventions. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atherosclerosis, inflammation, DNA, Mitochondrial