Glitazones and Endothelial Function (GATE)

This study has been terminated.
(Terminated at 50% enrollment due to recent concerns about rosiglitazone)
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
University of Calgary
ClinicalTrials.gov Identifier:
NCT00203632
First received: September 13, 2005
Last updated: October 30, 2008
Last verified: October 2008
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus
Drug: rosiglitazone/placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Trial of the Effect of Rosiglitazone as Add on to Metformin Therapy on Endothelial Function in Subjects With Type II DM

Resource links provided by NLM:


Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • 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 Measures:
  • 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.

Enrollment: 40
Study Start Date: September 2003
Study Completion Date: October 2007
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00203632

Locations
Canada, Alberta
Foothills Medical Centre
Calgary, Alberta, Canada, T2N 2T9
Sponsors and Collaborators
University of Calgary
GlaxoSmithKline
Investigators
Principal Investigator: Todd J Anderson, MD University of Calgary
Study Chair: Subodh Verma, MD, PhD University of Toronto
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00203632     History of Changes
Other Study ID Numbers: TPD 084385
Study First Received: September 13, 2005
Last Updated: October 30, 2008
Health Authority: Canada: Health Canada

Keywords provided by University of Calgary:
diabetes mellitus
endothelium
thiazolidinediones
atherosclerosis

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Rosiglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014