Type 2 Diabetes Mellitus and Atherosclerosis

November 27, 2012 updated by: Francesco Violi, University of Roma La Sapienza

Type 2 Diabetes Mellitus: Role of Inflammation and Innate Immunity in The Pathogenesis of Endothelial Dysfunction and Atherosclerosis

In individuals with Type 2 Diabetes (T2D) it has been obtained an outstanding improvement in the management of hyperglycemia, but it has not been achieved a similar result in the reduction of the atherosclerotic syndrome. The comprehension of the mechanisms that link over nutrition to inflammation and innate immune response can be important to understand the relationship between insulin resistance, diabetes mellitus and endothelial dysfunction. It will be investigated: 1) the role of Toll Like Receptors (TLR)s in the pathophysiology of T2D and associated atherosclerosis; 2) the role of aspirin and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor/s in the production of TxA2 and F2-isoprostanes in T2D patients; 3)new biomarkers associated to Diabetes and atherosclerosis including markers of endothelial dysfunction and cytokines.

It will be analyzed in isolated platelets from normal controls and/or diabetic patients the production of TxA2, isoprostanes and pro-inflammatory/thrombotic cytokines using aspirin and NADPHoxidase inhibitors.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Study design: prospective, controlled, randomized study. All eligible patients will be randomly assigned in a 1:1 manner to receive aspirin or placebo.

In each recruited subjects we will do:

  1. Anamnestic clinical information and Anthropometric measurements
  2. Electrocardiogram, echocardiogram and ultrasound assessment of carotid intima-media thickness (IMT) and flow-mediated dilatation (FMD)
  3. Ankle-Brachial Index measurement (ABI)
  4. blood samples from an antecubital vein after an overnight fast and urine samples at baseline, after 3 days and after 30 days of aspirin (100 mg/day) administration.

Laboratory Methods: Blood samples will be immediately centrifuged at 2,000 rpm for 20 min at 4°C, and the supernatant was collected and stored at -80°C until measurement. All measurements will be done blinded. Samples will be tested in duplicate, and those showing values above the standard curve will be re-tested with appropriate dilutions.Analysis of urinary and platelet isoprostane:Urinary PGF2α-III was measured by a previously described and validated EIA assay method. Ten millilitre urine were extracted on a C-18 SPE column; the purification was tested for recovery by adding a radioactive tracer (tritiated PGF2α-III) (Cayman chemical). The eluates were dried under nitrogen, recovered with 1ml of buffer, and assayed in a PGF2α-III specific EIA kit (Cayman chemical). Urinary PGF2α-III concentration was corrected for recovery and creatinine excretion and expressed as pg/mg of creatinine. PRP was then centrifuged 20 min at 800 g to concentrate platelets and the pellet was suspended in Tyrode buffer to obtain a final platelet concentration of 5x108/mL. PGF2α-III content was measured by a validated EIA assay method as previously described and expressed as pg/mg platelet protein.

Study Type

Interventional

Enrollment (Anticipated)

80

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Rome, Italy, 00161
        • Recruiting
        • Sapienza Università di Roma
        • Principal Investigator:
          • Francesco Violi, full Prof

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Type 2 Diabetes Mellitus (defined according to the criteria of the American Diabetes Association)
  • Sign of a written informed consent to participate to the interventional study

Exclusion Criteria:

  • Liver disease
  • Serious renal disorders (serum creatinine >2.5 mg/dL)
  • History or evidence of previous major vascular events (myocardial infarction, transient ischemic attack, stroke)
  • History of major bleeding
  • Autoimmune diseases
  • Cancer or present or recent infections
  • Use of non-steroidal anti-inflammatory drugs, drugs interfering with cholesterol metabolism, or vitamin supplements or antiplatelet drugs in the previous 30 days

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Aspirin
100 mg/day for 30 days
Drug: Aspirin
100 mg/day for 30 days
PLACEBO_COMPARATOR: Placebo
1 cp /day for 30 days
Drug: Placebo
1 cp day for 30 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes of isoprostanes after study drug administration.
Time Frame: 3 and 30 days
Mearuring levels of isoprostanes to understand if isoprostanes could play a crucial role in thrombus formation, independently from Aspirin mediated COX-1 inhibition, supporting their role in the phenomenon of the so call "aspirin resistance" in the setting of T2DM.
3 and 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Roma La Sapienza

Collaborators

University of Rome Tor Vergata

Investigators

  • Study Chair: Francesco Violi, Divisione di Prima Clinica Medica - Sapienza University of Rome

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2010

Primary Completion (ACTUAL)

January 1, 2011

Study Completion (ANTICIPATED)

December 1, 2012

Study Registration Dates

First Submitted

August 30, 2010

First Submitted That Met QC Criteria

November 29, 2010

First Posted (ESTIMATE)

November 30, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

November 28, 2012

Last Update Submitted That Met QC Criteria

November 27, 2012

Last Verified

November 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Diabetes and Oxidative Stress

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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