Glitazones and Endothelial Function (GATE)
Information source: University of Calgary
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diabetes Mellitus
Intervention: rosiglitazone/placebo (Drug)
Phase: Phase 3
Status: Terminated
Sponsored by: University of Calgary Official(s) and/or principal investigator(s):
Todd J Anderson, MD, Principal Investigator, Affiliation: University of Calgary
Subodh Verma, MD, PhD, Study Chair, Affiliation: University of Toronto
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.
Clinical Details
Official title: A Trial of the Effect of Rosiglitazone as Add on to Metformin Therapy on Endothelial Function in Subjects With Type II DM
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Primary outcome: 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 outcome: 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.
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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:
- Exclusion criteria includes, congestive heart failure (NYHA class III & IV or ejection
fraction less than 35%), poorly controlled hypertension (blood pressure > 160/90),
hypercholesterolemia (total cholesterol > 6. 2 mmol/l), hypertriglyceridemia
(triglycerides > 4. 0 mmol/l), poor or excellent control of DM (HgA1c <6 % or HbA1c >
10% respectively), known diabetic retinopathy, age at diagnosis of diabetes less than
25 years, current participation in another clinical trial and contraindications to
glitazones therapy, including renal (creatinine > 200 micromol/ L) or hepatic (ALT >
2. 5 times the upper limit of normal) impairment and/ or known intolerance to
glitazones. Patients must be stable on medications that affect endothelial function
for more than one month. This includes ACE-inhibitors, angiotensin receptor blockers,
statins, calcium channel blockers, hormone replacement therapy and anti-oxidant
vitamins, including folates. Patients on insulin will be excluded. Patients in whom it
is felt that attainment of better glucose control is required within 3 months will
also be excluded. Patients with stable coronary disease will be eligible for the study
as long as they are > one month post myocardial infarction, percutaneous intervention
or bypass surgery.
Locations and Contacts
Foothills Medical Centre, Calgary, Alberta T2N 2T9, Canada
Additional Information
Related publications: Hubacek J, Verma S, Shewchuk L, Ross SJ, Edwards A, Anderson TJ. Rationale and design of the Glitazones and the Endothelium (GATE) study: evaluation of rosiglitazone on endothelial function in patients with diabetes. Can J Cardiol. 2004 Dec;20(14):1449-53.
Starting date: September 2003
Ending date: October 2007
Last updated: October 25, 2007
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