Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE). A Multicenter Randomized Double-Blind Placebo-Controlled Trial of a Thiazolidinedione (TZD) or Placebo and of Vitamin D or Placebo In People With Type 2 Diabetes at Risk For Cardiovascular Disease.
- Conditions
- Type 2 Diabetes10012653
- Registration Number
- NL-OMON35554
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 525
1. Men or women with: a) newly detected type 2 diabetes based on a fasting plasma glucose >= 7.0 mmol/l (126 mg/dL) or a 2 hour plasma glucose (FPG) >= 11.1 mmol/l (200 mg/dL) on an oral glucose tolerance test, or b) a history of type 2 diabetes
2. Hemoglobin A1c (A1C) 6.5-9.5% inclusive (for assays with upper limit of normal of
6%) within one month of screening
3. A) Age >= 50 years and evidence of vascular disease defined as >=1of:
a) prior myocardial infarction
b) prior stroke
c) coronary, carotid or peripheral artery revascularization >= 4 years earlier
d) 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
B) Age >= 55 years and evidence of subclinical vascular disease defined as >=1 of:
a) microalbuminuria or proteinuria
b) history of treated or untreated hypertension with left ventricular hypertrophy
by electrocardiogram (ECG) or echocardiogram
c) >50% stenosis on any imaging of coronary, carotid or lower extremity arteries
d) ankle/brachial index <0.9
OR
C) Age >= 60 years and at least 2 of the following cardiovascular disease risk factors:
a) current tobacco use
b) LDL-c >=3.4 mmol/L (130 mg/dL) or on a lipid lowering medication
c) 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)
d) BP lowering medication use or untreated SBP >= 140 mmHg or DBP >= 95 mmHg
e) Waist to hip ratio > 1.0 for men and > 0.8 for women
4. On no insulin and on <= 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
5. A negative pregnancy test for all females of childbearing potential (i.e., ovulating,
pre-menopausal, and not surgically sterile) and agreement to use adequate birth
control (according to local regulations) throughout the study
6. Adherence >= 80% and tolerability to single-blind study medication during the run-in phase
7. Provision of signed and dated informed consent prior to any study procedures
1. Type 1 diabetes
2. Current need for insulin treatment
3. Symptomatic hyperglycemia requiring immediate therapy in the judgment of the
physician
4. An acute cardiovascular event within 30 days prior to randomization
5. 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
6. Any fracture within the past 1 year
7. Currently planned coronary, carotid or peripheral artery revascularization or cardiac valve surgery
8. 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
9. End stage renal disease requiring renal replacement therapy
10. Receiving drug therapy to treat liver disease
11. 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)
12. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level > 2.5
times the upper limit of normal
13. A prior heart transplant or awaiting a heart transplant
14. Previous or current hypercalcemia, hyperparathyroidism, osteomalacia or other
contraindication for vitamin D therapy
15. Regular use of or indication for greater than 400IU of vitamin D daily
16. Clinically or medically unstable with expected survival < 1 year
17. Unwillingness to permit sites to contact their primary physicians to communicate
information about the study and the participant*s data
18. Any other factor likely to limit protocol compliance or reporting of adverse events
19. Inability to discontinue a TZD (if taking one) in the judgement of the
physician/investigator
20. Contraindications to or history of hypersensitivity to the investigational products
21. History of renal stones within the past 2 years
22. Participation in another clinical trial of an investigational agent
23. Previous randomization in this study
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The composite cardiovascular primary outcome for the TZD research questions is<br /><br>the first occurrence of either: a) cardiovascular death; b) nonfatal myocardial<br /><br>infarction<br /><br>(MI); or c) nonfatal stroke.<br /><br>The composite primary outcome for the vitamin D research question is death or<br /><br>serious cancer requiring hospitalization, chemotherapy or surgery.</p><br>
- Secondary Outcome Measures
Name Time Method