thiazolidinedione intervention with vitamin d evaluation

Conditions: Diabetes Mellitus, Type 2

Summary: this study will answer two separate questions. the first question is to test the cardiovascular effects of long-term treatment with rosiglitazone or pioglitazone when used as part of standard of care compared to similar standard of care without rosiglitazone or pioglitazone in patients with type 2 diabetes who have a history of or are at risk for cardiovascular disease. the second question will compare the effects of long-term supplementation of vitamin d on death and cancer


Eligibility criteria:
inclusion criteria: * men or women with: a) newly detected type 2 diabetes based on a fasting plasma glucose greater than or equal to 7.0 mmol/l (126 mg/dl) or a 2 hour plasma glucose (fpg) greater than or equal to 11.1 mmol/l (200 mg/dl) on an oral glucose tolerance test, or b) a history of type 2 diabetes * hemoglobin a1c (a1c) 6.5-9.5% inclusive (for assays with upper limit of normal of 6%) within one month of screening * age ≥ 50 years and evidence of vascular disease defined as ≥1of: * prior myocardial infarction * prior stroke * coronary, carotid or peripheral artery revascularization ≥ 4 years earlier * previous documented myocardial ischemia on either an exercise stress test or on any cardiac imaging, or previous unstable angina with ecg changes or cardiac enzyme elevation or * age ≥ 55 years and evidence of subclinical vascular disease defined as ≥1 of: * microalbuminuria or proteinuria * history of treated or untreated hypertension with left ventricular hypertrophy by electrocardiogram (ecg) or echocardiogram * 50% stenosis on any imaging of coronary, carotid or lower extremity arteries * ankle/brachial index \<0.9 or * age ≥ 60 years and at least 2 of the following cardiovascular disease risk factors: * current tobacco use * ldl-c ≥3.4 mmol/l (130 mg/dl) or on a lipid lowering medication * hdl-c \< 1.0 mmol/l (40 mg/dl) for men and \< 1.3 mmol/l (50 mg/dl) for women or triglycerides ≥ 2.3 mmol/l (200 mg/dl) * bp lowering medication use or untreated sbp ≥ 140 mmhg or dbp ≥ 95 mmhg * waist to hip ratio \> 1.0 for men and \> 0.8 for women * on no insulin and on less than or equal to 2 anti-diabetes drugs where at least one drug is at or below the half-maximal dose (as indicated in the mop) with stable dosing for 10 weeks prior to screening exclusion criteria: * type 1 diabetes * current need for insulin treatment * symptomatic hyperglycemia requiring immediate therapy in the judgment of the physician * an acute cardiovascular event within 30 days prior to randomization * symptomatic heart failure (i.e. new york heart association class ii or higher) or any episode of previous pulmonary edema or known ejection fraction \< 0.4 or current use of loop diuretics * any fracture within the past 1 year * currently planned coronary, carotid or peripheral artery revascularization or cardiac valve surgery * coronary, carotid or peripheral artery revascularization within the 4 years prior to screening in the absence of angina, mi, or stroke in the intervening period * end stage renal disease requiring renal replacement therapy * receiving drug therapy to treat liver disease * a diagnosis of cancer (other than superficial squamous, basal cell skin cancer, or adequately treated cervical carcinoma in situ) in the past 3 years or current treatment for the active cancer (other than prophylactic) * alanine aminotransferase (alt) or aspartate aminotransferase (ast) level \> 2.5 times the upper limit of normal * a prior heart transplant or awaiting a heart transplant * previous or current hypercalcemia, hyperparathyroidism, osteomalacia or other contraindication for vitamin d therapy * regular use of or indication for greater than 400iu of vitamin d daily * clinically or medically unstable with expected survival \< 1 year * unwillingness to permit sites to contact their primary physicians to communicate information about the study and the participant's data * any other factor likely to limit protocol compliance or reporting of adverse events * inability to discontinue a tzd (if taking one) in the judgement of the physician/investigator * contraindications to or history of hypersensitivity to the investigational products * history of renal stones within the past 2 years * participation in another clinical trial of an investigational agent

Keywords: cardiovascular outcomes