Thiazolidinedione Intervention With Vitamin D Evaluation

• Status: Terminated
• Trial end date: 2010-11-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Collaborators: Academic Research Collaborator: Population Health Research Institute / Hamilton Health; Population Health Research Institute
• Treatments: 2,4-thiazolidinedione; Ergocalciferols; Pioglitazone; Rosiglitazone; Vitamin D; Vitamins

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