Diabetes Mellitus
Conditions
Keywords
diabetes mellitus, endothelium, thiazolidinediones, atherosclerosis
Brief summary
The purpose of the study is to determine if the addition of rosiglitazone to subjects with fair glucose control on other oral agents improves endothelial function, a surrogate marker of vascular health. It is hypothesized that improving whole body insulin sensitivity with combination therapy including rosiglitazone will restore the vascular actions of insulin and improve endothelium-dependent vasomotion more effectively than placebo in patients with diabetes mellitus.
Detailed description
The vascular endothelium has emerged as a critical determinant of cardiovascular health and disease, and improving endothelial function is an important target for therapy. Accumulating evidence suggest that insulin resistance in patients with diabetes and the metabolic syndrome may impair endothelial function, uncovering a proinflammatory, and proatherosclerotic vascular phenotype. The GATE study (Glitazones And The Endothelium) is a randomized, double blind study to evaluate the effects of rosiglitazone vs. placebo on endothelial function when employed as an add-on therapy in diabetic patients currently treated with oral therapy. We hypothesize that the PPAR-gamma agonist rosiglitazone, will improve endothelium-dependent vasodilatation, and that this effect will be related to improvements in insulin sensitivity, with concomitant reductions in whole body insulin resistance. Furthermore, the beneficial effects of rosiglitazone will be additive to existing oral therapies that may modulate endothelial function, such as metformin. Since endothelial dysfunction plays a pivotal role in the development and progression of atherosclerosis, these studies may provide the rationale and impetus for aggressive treatment of insulin resistant patients with glitazone therapy.
Interventions
DRUGrosiglitazone/placebo
Sponsors
GlaxoSmithKline
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All patients (both men and women) considered for participation in GATE study have to be non-insulin dependent diabetics (according to Canadian Diabetes Association criteria, namely a fasting serum glucose ≥ 7.0 mmol/L on two occasions, a casual glucose ≥ 11.1 mmol/l with symptoms, or a 2-h post-oral glucose tolerance test glucose of ≥ 11.1 mmol/l) with unsatisfactory glycemic control on oral therapy (HbA1c 6-10%).
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary end-point of the study is the percent change in forearm blood flow to acetylcholine in patients randomized to rosiglitazone compared with placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end-points include (i) the percent change in forearm blood flow to verapamil and the absolute change to both acetylcholine and verapamil and (ii) the relationship between HOMA-IR, CRP and endothelial function. | — |
Countries
Canada
Outcome results
None listed