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Does Pioglitazone Increase the Production of 15-EPI-Lipoxin A4?

NCT01040819 · Status: COMPLETED · Phase: PHASE4 · Type: INTERVENTIONAL · Enrollment: 25

Last updated 2016-06-22

Study results available
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Summary

Type-2 diabetes mellitus is a public health concern. Patients with type 2 diabetes mellitus are at high risk of developing cardiovascular complications. Diabetic patients are two to four-times more likely to develope cardiovascular disease. The mortality of diabetic patients with cardiovascular disease is much higher than in non-diabetic matched patients with cardiovascular disease. Recently, it has become apparent that not all anti-diabetic drugs have the same effect on the progression of atherosclerosis and on cardiovascular outcomes. There is a great need to understand the potential protective mechanisms of the various anti-diabetic drugs in order to decrease their risk for cardiovascular morbidity and mortality. In addition to increasing insulin sensitivity, Pioglitazone (PIO) has anti-inflammatory properties. However, the underlying mechanisms of these anti-inflammatory (and probably anti-atherosclerotic) effects of PIO are unknown. We have shown in the rat that 3-day pretreatment with PIO increases myocardial cyclooxygenase-2 (COX2) activity and levels of both 6-keto-PGF1a, the stable metabolite of prostacyclin (PGI2) and 15-epi-lipoxin A4, a lipid mediator with a strong anti-inflammatory properties. Prostacyclin inhibits platelet aggregation and causes vasodilatation. Increased levels of 6-keto-PGF1a and 15-epi-lipoxin A4 may thus be the explanation for the anti-inflammatory and anti-atherosclerosis effects of PIO. Several clinical studies have shown that COX2 inhibition is associated with increased cardiovascular events. Thus, augmenting COX2 activity and the production of prostacyclin and 15-epi-lipoxin A4 may have potential favorable effects. The purpose of the study is to test whether PIO therapy is associated with an increase in serum and/or urine levels of 6-keto-PGF1a and 15-epi-lipoxin A4 in patients with diabetes mellitus type 2.

Conditions

Interventions

DRUG

Pioglitazone

Patients will receive PIO 15 mg/d for one month, then 55 patients continue with the same dose for one additional month, and in 55 patients the dose will be increased to 30 mg/d for an additional one month. Other non-diabetes drugs should not be changed. Other hypoglycemic agents, including insulin may be adjusted, if clinically indicated. NSAID, COX2 inhibitors, aspirin \>162 mg/d, steroids and prostaglandin analogs will be prohibited.

Sponsors & Collaborators

  • Baylor College of Medicine

    lead OTHER

Principal Investigators

  • Yochai Birnbaum, MD · Baylor College of Medicine

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Model
PARALLEL

Eligibility

Min Age
21 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2010-02-28
Primary Completion
2011-10-31
Completion
2011-12-31

Countries

  • United States

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01040819 on ClinicalTrials.gov