Mesoglycan, Vascular Reactivity and Metabolic Syndrome

NCT ID: NCT02254850

Last Updated: 2014-10-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-31

Study Completion Date

2014-06-30

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.

Conditions

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Metabolic Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Mesoglycan

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).

Group Type EXPERIMENTAL

Flow Mediated Dilation

Intervention Type PROCEDURE

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.

Mesoglycan

Intervention Type DRUG

The Patients firstly underwent to intramuscular administration of 1 vial only, containing: Mesoglycan 30mg/ml.

Mesoglycan

Intervention Type DRUG

The patients underwent to oral treatment with 1 capsule, administered bis in die for a period of 90 days, containing: Mesoglycan 50 mg.

Placebo

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).

Group Type PLACEBO_COMPARATOR

Flow Mediated Dilation

Intervention Type PROCEDURE

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.

Placebo

Intervention Type DRUG

The Patients firstly underwent to intramuscular administration only of 1 vial containing inactive ingredients: sodium chloride, chlorocresol, water for injections.

Placebo

Intervention Type DRUG

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.

Interventions

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Flow Mediated Dilation

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.

Intervention Type PROCEDURE

Mesoglycan

The Patients firstly underwent to intramuscular administration of 1 vial only, containing: Mesoglycan 30mg/ml.

Intervention Type DRUG

Mesoglycan

The patients underwent to oral treatment with 1 capsule, administered bis in die for a period of 90 days, containing: Mesoglycan 50 mg.

Intervention Type DRUG

Placebo

The Patients firstly underwent to intramuscular administration only of 1 vial containing inactive ingredients: sodium chloride, chlorocresol, water for injections.

Intervention Type DRUG

Placebo

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.

Intervention Type DRUG

Other Intervention Names

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FMD Mesoglycan Intramuscular injecion Mesoglycan Oral Treatment Placebo Intramuscular Injection Placebo Oral Treatment

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Federico II University

OTHER

Sponsor Role lead

Responsible Party

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Ugo Oliviero

Medical Doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ugo Oliviero, MD

Role: PRINCIPAL_INVESTIGATOR

Federico II University-Dipartimento di Scienze Mediche Traslazionali

Locations

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Ugo Oliviero

Via Pansini, 5, Napoli, Italy

Site Status

Countries

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Italy

References

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Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005 Oct 25;112(17):2735-52. doi: 10.1161/CIRCULATIONAHA.105.169404. Epub 2005 Sep 12. No abstract available.

Reference Type BACKGROUND
PMID: 16157765 (View on PubMed)

Reaven G. The metabolic syndrome or the insulin resistance syndrome? Different names, different concepts, and different goals. Endocrinol Metab Clin North Am. 2004 Jun;33(2):283-303. doi: 10.1016/j.ecl.2004.03.002.

Reference Type BACKGROUND
PMID: 15158520 (View on PubMed)

Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med. 1999 May;16(5):442-3. doi: 10.1046/j.1464-5491.1999.00059.x. No abstract available.

Reference Type BACKGROUND
PMID: 10342346 (View on PubMed)

National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002 Dec 17;106(25):3143-421. No abstract available.

Reference Type BACKGROUND
PMID: 12485966 (View on PubMed)

Ridker PM, Wilson PW, Grundy SM. Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation. 2004 Jun 15;109(23):2818-25. doi: 10.1161/01.CIR.0000132467.45278.59.

Reference Type BACKGROUND
PMID: 15197153 (View on PubMed)

Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007 Mar 13;115(10):1285-95. doi: 10.1161/CIRCULATIONAHA.106.652859. No abstract available.

Reference Type BACKGROUND
PMID: 17353456 (View on PubMed)

Prieto D, Contreras C, Sanchez A. Endothelial dysfunction, obesity and insulin resistance. Curr Vasc Pharmacol. 2014 May;12(3):412-26. doi: 10.2174/1570161112666140423221008.

Reference Type BACKGROUND
PMID: 24846231 (View on PubMed)

Anderson TJ. Nitric oxide, atherosclerosis and the clinical relevance of endothelial dysfunction. Heart Fail Rev. 2003 Jan;8(1):71-86. doi: 10.1023/a:1022199021949.

Reference Type BACKGROUND
PMID: 12652161 (View on PubMed)

Forconi S, Battistini N, Guerrini M, Passero SG for the SIAM Group. A randomized, ASA-controlled trial of mesoglycan in secondary prevention after cerebral ischemic events. Cerebrovasc Dis 1995; 5:334-341.

Reference Type BACKGROUND

Orefice G, Brancaccio V, Coppola G et al. Comparative effects of mesoglycan and ticlopidine treatment on some coagulative parameters in patients with previous ischemic stroke: results of a randomized controlled trial. Current Therapeutic Research 2002; 63:337-343.

Reference Type BACKGROUND

Nenci GG, Gresele P, Ferrari G, Santoro L, Gianese F; Mesoglycan Intermittent Claudication Group. Treatment of intermittent claudication with mesoglycan--a placebo-controlled, double-blind study. Thromb Haemost. 2001 Nov;86(5):1181-7.

Reference Type BACKGROUND
PMID: 11816704 (View on PubMed)

Charakida M, Masi S, Luscher TF, Kastelein JJ, Deanfield JE. Assessment of atherosclerosis: the role of flow-mediated dilatation. Eur Heart J. 2010 Dec;31(23):2854-61. doi: 10.1093/eurheartj/ehq340. Epub 2010 Sep 23.

Reference Type BACKGROUND
PMID: 20864485 (View on PubMed)

Tufano A, Arturo C, Cimino E, Di Minno MN, Di Capua M, Cerbone AM, Di Minno G. Mesoglycan: clinical evidences for use in vascular diseases. Int J Vasc Med. 2010;2010:390643. doi: 10.1155/2010/390643. Epub 2010 Aug 31.

Reference Type BACKGROUND
PMID: 21152191 (View on PubMed)

Juhan-Vague I, Morange PE, Alessi MC. The insulin resistance syndrome: implications for thrombosis and cardiovascular disease. Pathophysiol Haemost Thromb. 2002 Sep-Dec;32(5-6):269-73. doi: 10.1159/000073579.

Reference Type BACKGROUND
PMID: 13679655 (View on PubMed)

Other Identifiers

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Mesoglicano 29/13

Identifier Type: -

Identifier Source: org_study_id

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