Type 2 Diabetes Mellitus and Atherosclerosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by University of Roma La Sapienza
Sponsor:
Collaborator:
University of Rome Tor Vergata
Information provided by (Responsible Party):
Francesco Violi, University of Roma La Sapienza
ClinicalTrials.gov Identifier:
NCT01250340
First received: August 30, 2010
Last updated: November 27, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Aspirin
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Type 2 Diabetes Mellitus: Role of Inflammation and Innate Immunity in The Pathogenesis of Endothelial Dysfunction and Atherosclerosis

Resource links provided by NLM:


Further study details as provided by University of Roma La Sapienza:

Primary Outcome Measures:
  • Changes of isoprostanes after study drug administration. [ Time Frame: 3 and 30 days ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 80
Study Start Date: August 2010
Estimated Study Completion Date: December 2012
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aspirin
100 mg/day for 30 days
Drug: Aspirin
100 mg/day for 30 days
Other Name: Aspirin
Placebo Comparator: Placebo
1 cp /day for 30 days
Drug: Placebo
1 cp day for 30 days
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01250340

Contacts
Contact: Francesco Violi, Full Prof +39-06-4461933 francesco.violi@uniroma1.it
Contact: Stefania Basili, Ass Prof +39-06-49974678 stefania.basili@uniroma1.it

Locations
Italy
Sapienza Università di Roma Recruiting
Rome, Italy, 00161
Contact: Francesco Violi, Full Prof    +39-06-4461933    francesco.violi@uniroma1.it   
Contact: Stefania Basili, Ass Prof    +39-06-49974678    stefania.basili@uniroma1.it   
Principal Investigator: Francesco Violi, full Prof         
Sponsors and Collaborators
University of Roma La Sapienza
University of Rome Tor Vergata
Investigators
Study Chair: Francesco Violi Divisione di Prima Clinica Medica - Sapienza University of Rome
  More Information

No publications provided by University of Roma La Sapienza

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Francesco Violi, Full professor of internal medicine, University of Roma La Sapienza
ClinicalTrials.gov Identifier: NCT01250340     History of Changes
Other Study ID Numbers: Diabetes and Oxidative Stress
Study First Received: August 30, 2010
Last Updated: November 27, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by University of Roma La Sapienza:
Diabetes
Isoprostanes
Thromboxane
Aspirin

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Diabetes Mellitus
Diabetes Mellitus, Type 2
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics

ClinicalTrials.gov processed this record on August 21, 2014