Mesoglycan, Vascular Reactivity and Metabolic Syndrome

Study Overview
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Brief Summary
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The purpose of the study was to characterize the action of mesoglycan on vascular endothelium through the non-invasive assessment of vascular reactivity humeral artery by comparing effects of mesoglycan on Flow Mediated Dilatation (FMD) of the humeral artery between a group of patients with metabolic syndrome assuming placebo and a group of patient with metabolic syndrome assuming mesoglycan; firstly after administration of the drug/placebo intramuscularly, and then, in a study of medium-term after oral intake of drug/placebo. The selection of patients with metabolic syndrome is related to the fact that this syndrome is associated with alterations in endothelial function and a high incidence of cardiovascular events. So it is a condition that offers the opportunity to explore the hypothesis that the mesoglycan may have a favorable effect on early vascular alterations that precede clinical events.

Detailed Description
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The subjects were enrolled in a double blind randomized way, according to a 2: 1 ratio, to intramuscular treatment with mesoglycan or placebo. Patients performed the study of the Flow Mediated Dilation (FMD) according to the following scheme: FMD baseline FMD 2 hours after the administration of 2 vials of mesoglycan or placebo intramuscularly FMD 6 hours after intramuscular administration. Nextly, both patients treated with mesoglycan vials and placebo vials continued therapy for assuming mesoglycan or placebo, per os, bis in die, for 90 days. At the end of this period of oral therapy (mesoglycan or placebo in a 2: 1 ratio), all patients performed FMD again. The patients who were taking any specific therapy (eg antihypertensive drugs) the Placebo was administered in addition to their standard therapy. The vascular reactivity evaluation adopted was the Flow Mediated Dilatation (FMD). After a period of fasting and rest for at least 6 hours, the study of FMD was performed using a high-resolution ultrasound system, equipped with a 7.5 Megahertz linear probe under ECG monitoring. After a rest period of at least 10 minutes on a bed in supine decubitus in an air-conditioned room, the sensor was placed on humeral artery, 3-5 cm above the elbow, and held the same position during the examination through an arm mechanically connected. They were performing a number of longitudinal sections and measured the internal diameter of the vessel, defined as the distance between the top edge of the echo produced by the interface between the lumen and the anterior wall of the vessel and the top edge of the echo produced by the interface between the lumen and the rear wall of the vessel. The inner diameter of the vessel was measured several times, on the R wave of the ECG, and a pc software calculated the average value. The flow rate was measured with the sample volume placed in the center of the vase with a 60 ° angle between the ultrasound beam and the longitudinal axis of the vessel. The post-ischemic vasodilation was induced using a sphygmomanometer placed on the forearm, distal to the elbow crease, kept inflated to 250 mmHg for 5 minutes. The flow rate, always with a correction angle of 60 °, was recorded immediately after the desufflation; the diameter of the brachial artery, it was measured several times after desufflation (for 60-90 seconds). Nextly, the FMD was calculated as the percentage difference between the maximum diameter of the post-ischemic reached and the mean diameter of the base of the vessel.

Official Title
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The Mesoglycan and Vascular Reactivity in the Metabolic Syndrome

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Procedure: Flow Mediated Dilation
* Drug: Mesoglycan
* Drug: Mesoglycan
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 3 or more of the following criteria of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Increased abdominal circumference ≥102 cm in man, ≥88 cm in women Triglycerides ≥150 mg / dL HDL-cholesterol <40 mg / dL in men, <50 mg / dL in women Systolic blood pressure> 130 mm Hg or diastolic blood pressure> 85 mm Hg Blood glucose> 100 mg / dL Exclusion Criteria: Indication for cardiac surgery or surgeries performed by less than 3 months Under the age of 18 years Age greater than 65 years Inability to perform periodic inspections Presence of malignancy and serious heart diseases. Hemorrhagic diathesis and diseases. Hypersensitivity to mesoglycan, heparin and heparinoids. Type 1 diabetes and type 2 Pregnancy and / or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesoglycan<br>The Patients firstly underwent to intramuscular administration of 1 vial only, containing: Mesoglycan 30mg/ml and inactive ingredients: sodium chloride, chlorocresol, water for injections. Nextly the patients underwent to oral treatment with 1 capsule, administered bis in die for a period of 90 days, containing: Mesoglycan 50 mg and Inactive ingredients: lactose monohydrate, corn starch, croscarmellose sodium, magnesium stearate, gelatin, titanium dioxide, erythrosine. Patients also performed Flow Mediated Dilation (FMD). | Procedure: Flow Mediated Dilation<br>* Patients performed FMD by an high-resolution ultrasound linear probe in a supine decubitus and conditioned room.The probe was placed on humeral artery and connected to a mechanically arm. Then were performed several measurement s of the internal diameter of the vessel (edge to edge distance), on the R wave of the ECG, and software calculated the average value.The post-ischemic vasodilation was induced using a sphygmomanometer placed on the forearm, distal to the elbow crease, kept inflated to 250 mmHg for 5 minutes. The flow rate was recorded immediately after the desufflation; the diameter of the brachial artery was measured several times after desufflation (for 60-90 seconds). Nextly, the FMD was calculated as the percentage difference between the maximum diameter of the post-ischemic reached and the mean diameter of the vessel.<br>* Other names: FMD;Drug: Mesoglycan<br>* The Patients firstly underwent to intramuscular administration of 1 vial only, containing: Mesoglycan 30mg/ml.<br>* Other names: Mesoglycan Intramuscular injecion;Drug: Mesoglycan<br>* The patients underwent to oral treatment with 1 capsule, administered bis in die for a period of 90 days, containing: Mesoglycan 50 mg.<br>* Other names: Mesoglycan Oral Treatment;|
| Placebo Comparator: Placebo<br>The Patients firstly underwent to intramuscular administration only of 1 vial containing inactive ingredients: sodium chloride, chlorocresol, water for injections. Nextly the patients underwent to oral treatment with 1 capsule, administered bis in die for a period of 90 days, containing inactive ingredients: lactose monohydrate, corn starch, croscarmellose sodium, magnesium stearate, gelatin, titanium dioxide, erythrosine. Patients also performed Flow Mediated Dilation (FMD). | Procedure: Flow Mediated Dilation<br>* Patients performed FMD by an high-resolution ultrasound linear probe in a supine decubitus and conditioned room.The probe was placed on humeral artery and connected to a mechanically arm. Then were performed several measurement s of the internal diameter of the vessel (edge to edge distance), on the R wave of the ECG, and software calculated the average value.The post-ischemic vasodilation was induced using a sphygmomanometer placed on the forearm, distal to the elbow crease, kept inflated to 250 mmHg for 5 minutes. The flow rate was recorded immediately after the desufflation; the diameter of the brachial artery was measured several times after desufflation (for 60-90 seconds). Nextly, the FMD was calculated as the percentage difference between the maximum diameter of the post-ischemic reached and the mean diameter of the vessel.<br>* Other names: FMD;Drug: Placebo<br>* The Patients firstly underwent to intramuscular administration only of 1 vial containing inactive ingredients: sodium chloride, chlorocresol, water for injections.<br>* Other names: Placebo Intramuscular Injection;Drug: Placebo<br>* The patients underwent to oral treatment with 1 capsule, administered bis in die for a period of 90 days, containing inactive ingredients: lactose monohydrate, corn starch, croscarmellose sodium, magnesium stearate, gelatin, titanium dioxide, erythrosine.<br>* Other names: Placebo Oral Treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of FMD | Verify if taken chronically mesoglycan 1 cp morning and evening for 90 days change compared to placebo vascular reactivity in subjects with metabolic syndrome (increased FMD in the treated group compared to baseline after 90 days of therapy) . | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of FMD | Verify if the mesoglycan administered intramuscularly change the vascular reactivity compared to placebo in subjects with metabolic syndrome (increased FMD from baseline in 2 and 6 hours after intramuscular administration) | 2 and 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesoglycan, Metabolic Syndrome, Flow Mediated Dilation