Type 2 Diabetes Mellitus and Atherosclerosis

NCT ID: NCT01250340

Last Updated: 2012-11-28

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

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-08-31

Study Completion Date

2012-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Type 2 Diabetes Mellitus

Keywords

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Diabetes Isoprostanes Thromboxane Aspirin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Aspirin

100 mg/day for 30 days

Group Type EXPERIMENTAL

Aspirin

Intervention Type DRUG

100 mg/day for 30 days

Placebo

1 cp /day for 30 days

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

1 cp day for 30 days

Interventions

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Aspirin

100 mg/day for 30 days

Intervention Type DRUG

Placebo

1 cp day for 30 days

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Rome Tor Vergata

OTHER

Sponsor Role collaborator

University of Roma La Sapienza

OTHER

Sponsor Role lead

Responsible Party

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Francesco Violi

Full professor of internal medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Francesco Violi

Role: STUDY_CHAIR

Divisione di Prima Clinica Medica - Sapienza University of Rome

Locations

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Sapienza Università di Roma

Rome, Italy, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Francesco Violi, Full Prof

Role: CONTACT

Phone: +39-06-4461933

Email: [email protected]

Stefania Basili, Ass Prof

Role: CONTACT

Phone: +39-06-49974678

Email: [email protected]

Facility Contacts

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Francesco Violi, Full Prof

Role: primary

Stefania Basili, Ass Prof

Role: backup

References

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Carnevale R, Iuliano L, Nocella C, Bartimoccia S, Trape S, Russo R, Gentile MC, Cangemi R, Loffredo L, Pignatelli P, Violi F; IPINET group. Relationship between platelet and urinary 8-Iso-PGF2alpha levels in subjects with different degrees of NOX2 regulation. J Am Heart Assoc. 2013 Jun 14;2(3):e000198. doi: 10.1161/JAHA.113.000198.

Reference Type DERIVED
PMID: 23770972 (View on PubMed)

Cangemi R, Pignatelli P, Carnevale R, Nigro C, Proietti M, Angelico F, Lauro D, Basili S, Violi F. Platelet isoprostane overproduction in diabetic patients treated with aspirin. Diabetes. 2012 Jun;61(6):1626-32. doi: 10.2337/db11-1243. Epub 2012 Mar 16.

Reference Type DERIVED
PMID: 22427378 (View on PubMed)

Other Identifiers

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Diabetes and Oxidative Stress

Identifier Type: -

Identifier Source: org_study_id