Effects of ROSIglitazone on Inflammatory Markers and Adipokines in Diabetic Patients Using an Angiotensin Receptor Blocker (TELmisartan) - The ROSITEL Study

NCT00486187 | Completed

• 1 other identifier: AVD105195
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the ROSITEL study is to assess the effects of rosiglitazone, as compared to standard oral therapies for diabetes (metformin/sulfonylurea), on inflammatory markers and adipokine levels in diabetic patients using an angiotensin receptor blocker (ARB). We hypothesize that ARB-treated diabetic patients receiving rosiglitazone will experience greater reductions in vascular inflammation and levels of leptin and resistin, associated with increased adiponectin levels, compared to a metformin/sulfonylurea regimen, and that these benefits will result in part, from greater improvements in insulin sensitivity in the rosiglitazone group.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes Mellitus; Thiazolidinediones; Rosiglitazone; Adipokine; Inflammation; Cardiometabolic risk; Angiotensin receptor blocker

Outcome Measures

Primary Outcomes (1)

• Change in adiponectin level in the rosiglitazone vs. metformin/sulfonylurea arms

  12 weeks

Secondary Outcomes (1)

• Secondary end-points include changes in leptin, resistin, hs-CRP, IL-6, MMP-9, ICAM-1, insulin sensitivity (as estimated by the HOMA technique), HbA1c, and lipid levels in the rosiglitazone vs. metformin/sulfonylurea arms

  12 weeks

Study Arms (2)

1

EXPERIMENTAL

Treatment-naive subjects randomly assigned to rosiglitazone (4 mg/day force titrated to 8 mg/day). Subjects taking metformin before randomization were randomly assigned to the addition of rosiglitazone (4 mg/day force titrated to 8 mg/day). Subjects taking glyburide before randomization were randomly assigned to the addition of rosiglitazone (4 mg/day).

Drug: rosiglitazone

2

ACTIVE COMPARATOR

Treatment-naive subjects randomly assigned to metformin (250 mg twice per day \[BID\] titrated to 500 mg BID if baseline A1C ≥7.5% and ≤8.0%, or 500 mg BID titrated to 1 g BID if baseline A1C \>8.0%). Subjects taking metformin before randomization were randomly assigned to the addition of glyburide (2.5 mg BID titrated to 5 mg BID if baseline A1C ≥7.5% and ≤8.0%, or 5 mg BID titrated to 10 mg BID if baseline A1C \>8.0%). Subjects taking glyburide before randomization were randomly assigned to the addition of metformin (250 mg BID titrated to 500 mg BID if baseline A1C ≥7.5% and ≤8.0% or 500 mg BID titrated to 1 g BID if baseline A1C \>8.0%).

Drug: metformin or sulfonylurea

Interventions

rosiglitazone DRUG

Also known as: Avandia

1

metformin or sulfonylurea DRUG

2

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes
• Hemoglobin A1c (HbA1c) level greater or equal to 0.075
• Treatment naïve (no current oral anti-diabetic therapy) or on monotherapy with either metformin or any sulfonylurea
• Must meet one of the following:
• Already on an angiotensin receptor blocker (ARB for hypertension and/or microalbuminuria OR
• If not on an ARB: SBP\>129 mm Hg and/or DBP \>79 mm Hg And/Or albumin to creatinine ratio (ACR) \> 2.0 mg/mmol in men or \> 2.8 mg/mmol in women

You may not qualify if:

• Women who are pregnant, breast feeding, or not using a reliable method of contraception
• Clinical signs of congestive heart failure or measured left ventricular ejection fraction \<40%
• Hemodynamically significant valvular heart disease or hypertrophic obstructive cardiomyopathy
• Insulin-dependent diabetes mellitus
• Use of any PPAR-ỵ agonist (Rosiglitazone or Pioglitazone)
• Renal dysfunction (creatinine \> 1.8 x ULN)
• Hepatic disease (liver function test \>1.5 x ULN \[upper limit normal\])
• Other significant laboratory abnormalities that the investigator feels may compromise the patient's safety by participation in the study
• History of systemic inflammatory disease (rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematous), myositis/myopathic process, or cancer)
• HIV
• Use of steroids or chemotherapy drugs within the past year or chronic use of nonsteroidal anti-inflammatory drugs besides aspirin (use for \> 2 weeks within the past year);
• Patients on potassium sparing-diuretics
• Treatment with excluded medications prior to or at the time of randomization
• Known hypersensitivity to Rosiglitazone, or ARB's
• Participation in another clinical study concurrently or within the 30-day phase prior to screening for entry into the present study

Sponsors & Collaborators

• Dr. Milan Gupta: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Partners Research

Brampton, Ontario, L6V 1B4, Canada

Location

Related Publications (1)

• Gupta M, Teoh H, Kajil M, Tsigoulis M, Quan A, Braga MF, Verma S. The effects of rosiglitazone on inflammatory biomarkers and adipokines in diabetic, hypertensive patients. Exp Clin Cardiol. 2012 Winter;17(4):191-6.

  PMID: 23592934 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Inflammation

Interventions

Rosiglitazone; Metformin; Sulfonylurea Compounds

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines; Urea; Amides; Sulfones

Study Officials

• Milan K Gupta, MD

  Partners Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 12, 2007
• First Posted: June 14, 2007
• Study Start: April 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: January 28, 2016

Record last verified: 2016-01

Locations

CA (1)