Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) A Multicenter Randomized Double-Blind Placebo-Controlled Trial of a Thiazolidinedione or Placebo and of Vitamin D or Placebo In People With Type 2 Diabetes at Risk For Cardiovascular Disease - TIDE

• Conditions: - Incidence of CV outcomes compared to placebo for the TZD class as a whole, rosiglitazone (RSG), and pioglitazone (PIO) when added to the therapeutic regimen of a person with type 2 diabetes who has additional risk factors for CV events. - Determine whether adding vitamin D in such individuals is superior to adding placebo with respect to reducing the incidence of death or serious cancers requiring hospitalization, chemotherapy or surgery compared to placebo.; MedDRA version: 9.1Level: PTClassification code 10012601Term: Diabetes mellitus

• Registration Number: EUCTR2008-005030-73-IE
• Lead Sponsor: GlaxoSmithKline

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12-03
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 16000

Inclusion Criteria

1. Men or women with:
a) newly detected type 2 diabetes based on a fasting plasma glucose higher than 7.0 mmol/l (126 mg/dL) or a 2 hour plasma glucose higher than 11.1 mmol/l (200 mg/dL) on an oral glucose tolerance test, or b) a history of type 2 diabetes
2. A1C 6.5-9.5% inclusive
3. A) Age = 50 years and evidence of vascular disease(at least 1):
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 (at least 1):
a) microalbuminuria or proteinuria
b) history of treated or untreated hypertension with left ventricular hypertrophy by 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 CVD risk factors:
a) current tobacco use
b) LDL-C =3.4 mmol/L (130 mg/dL)
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 less or equal than 2 anti-diabetes drugs (OAD) 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

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 of 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 indication or contraindication for vitamin D therapy
15. Clinically or medically unstable with expected survival < 1 year
16. Unwillingness to permit sites to contact their primary physicians to communicate information about the study and the participant’s data
17. Any other factor likely to limit protocol compliance or reporting of adverse events
18. Inability to discontinue a TZD (if taking one) in the judgement of the physician/investigator
19. Contraindications to or history of hypersensitivity to the investigational products
20. History of renal stones within the past 2 years
21. Participation in another clinical trial of an investigational agent
22. Previous randomization in this study

French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified