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

Completed · Phase 4

Conditions studied: Type 2 Diabetes Mellitus

In brief

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.

Key facts

Study ID

NCT01040819

Run by

Baylor College of Medicine

People needed

25

Starts

2010-02-01

Expected to finish

2011-12-01

Last updated by the study team

2016-06-22

Who can join

Age: 21 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Men and women > 21 years old with type 2 diabetes Mellitus and otherwise stable medical conditions

You may not qualify if…

• Serum creatinine >= 1.5 mg/dl and/or renal failure
• NYHA class III or IV heart failure
• Known intolerance to TZD
• Current use of NSAID, COX-2 inhibitors, steroids (oral, topical and inhalation) or immunosuppressive therapy
• Aspirin > 162 mg/d
• Recent myocardial infarction, ACS, or stroke <=3 months)
• Significant comorbid conditions such as: cancer (not cured), end stage renal disease, severe obstructive lung disease, cirrhosis, etc)
• Recent (<1 month) infection
• Recent CABG or PCI (<3 months)
• Use of prostaglandin analogs (i.e., iloprost)
• Active inflammatory disease
• Current use of TZD
• Pregnancy
• Osteoporosis or high risk for bone fracture. Use of other antihyperglycemic agents is not an exclusion criterion. HbA1c and glucose levels will not restrict enrollment.

Where it is running

• Baylor Clinics — Houston, Texas, United States
• Baylor College of Medicine — Houston, Texas, United States

Full record on ClinicalTrials.gov

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