Clinical trial NCT00443755
Conditions: Type 2 Diabetes Insulin Resistance Metabolic Syndrome
Keywords: Inflammatory cytokine Cardiovascular Disease Thrombotic factors Dyslipidemia
Sponsor: Mayo Clinic
Start date: 2005-08-01; Completion date: 2010-08-01
Enrollment: 28 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The objective of this study is to determine whether targeted pharmacological improvement of insulin sensitivity will normalize the associated elevations of thrombotic and inflammatory cardiovascular disease (CVD) biomarkers in individuals with insulin resistance.

Detailed description:
Individuals with diabetes mellitus (DM) are disproportionately affected by atherothrombotic disorders, including cardiovascular, cerebrovascular, and peripheral vascular diseases. Atherothrombotic disease risk and mortality are also increased with metabolic syndrome, a constellation of risk factors present in more than 34% of adults, even in absence of diabetes. Yet, large clinical trials of diabetes therapies have shown that conventional cardiovascular disease (CVD) risk factors, specifically hyperglycemia and hypertension, do not fully account for increased CVD risk associated with DM.

There may be an etiologic link among insulin resistance, inflammation and thrombotic events. This study seeks to determine if certain two diabetes medications (the insulin sensitizing medications) will affect certain biomarkers (or laboratory tests) for CVD in individuals with untreated DM or impaired fasting glucose.

Patients will be screened for inclusion into this this double-blinded, randomized), placebo-controlled study. If inclusion criteria are met and exclusion criteria not met, patients will be enrolled in the the study. Half of the subjects will be randomized (like the flip of a coin) to take two insulin sensitizing, anti-diabetic drugs pioglitazone (Actos) and metformin (Glucophage) taken together for three months and the other half of the subjects will take corresponding placebo (dummy) tablets.

Laboratory measurements will be obtained on the morning(s) following the two in-patient overnight stays in the Mayo Clinic Clinical Research Unit. The first stay will be at baseline and the second stay will be 3 months after baseline. Insulin sensitivity will be measured in the morning following a standardized meal the preceding night, and after an overnight fast.

The changes (from baseline to 3 months) in insulin sensitivity, glycemic control, the lipid profile, thrombotic markers and inflammatory markers will be determined and compared between the two arms of the study (placebo versus insulin sensitizing drugs).

Arms: arm 1: Two insulin sensitizing drugs will be taken together for 3 months; metformin 1000 mg twice daily plus pioglitazone 45 mg daily. arm 2: Placebo tablets were used to match the active comparator drugs and dosing regimen.
Interventions: intervention 1: metformin intervention 2: pioglitazone intervention 3: Placebo
Intervention descriptions: intervention 1: To minimize side effects the metformin will be initiated at 500 mg twice daily with meals and increased to 1 gm twice daily with meals after two weeks and continue to a total of 3 months of dosing. intervention 2: To minimize side effects, the pioglitazone will be initiated at 30 mg daily and increased to 45 mg daily after two weeks, and continue to a total of 3 months of dosing. intervention 3: Placebo tablets matching the metformin and pioglitazone tablets are given in the same regimen as the active drug arm for 3 months.

Protocol documents: