Type 2 Diabetes MellitusNCT00486187
Effects of ROSIglitazone on Inflammatory Markers and Adipokines in Diabetic Patients Using an Angiotensin Receptor Blocker (TELmisartan) - The ROSITEL Study
A study testing rosiglitazone and metformin or sulfonylurea in people with Type 2 Diabetes Mellitus, run by Dr. Milan Gupta at 1 site in Canada.
Trial 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). Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- rosiglitazone and metformin or sulfonylurea
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2006to Jun 2009
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 17Show fewer
- 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
- Unwilling to provide written informed consent for study participant and/or
- Unreliability as a study participant as based on the investigator's prior knowledge of the patient, such as the inability or willingness to participate in or complete the study or the presence of concurrent physical or psychological disorders that may make it impractical for the patient to participate in or complete the study.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
Type 2 diabetes is a chronic and progressive disease that is strongly associated with all-cause and cardiovascular mortality. The United Kingdom Prospective Diabetes Study (UKPDS) demonstrated that glycemic control alone only modestly reduces the risk of macrovascular disease among type 2 diabetic patients . Insulin resistance, which has been identified as an important underlying or associated factor in the pathogenesis of type 2 diabetes, is the main proposed mechanism responsible for the accelerated atherosclerosis noted in this population.
Evidence continues to accumulate supporting the role of chronic subclinical vascular inflammation as a central component in the development of atherosclerosis, insulin resistance and type 2 diabetes. Markers of subclinical inflammation, in particular C-reactive protein (CRP) and interleukin-6 (IL-6), have been shown to be independent predictors of both diabetes and cardiovascular risk. More recently, the visceral adipocyte has been recognized to produce a number of metabolically and hormonally active substances, collectively called adipokines. The adipokine adiponectin may have antiatherogenic and anti-inflammatory properties. High levels of adiponectin seem to be associated with protection against type 2 diabetes and atherosclerosis via anti-inflammatory pathways. Unlike adiponectin, leptin and resistin are examples of adipokines that seem to be associated with the development of both atherosclerosis and insulin resistance.
Rosiglitazone is a thiazolidinedione drug that is approved for the treatment of type 2 diabetes. As a nuclear peroxisome proliferator-activated receptor-γ agonist, rosiglitazone reduces insulin resistance, thereby sensitizing the liver, muscle, and adipose tissue to the actions of circulating insulin. Treatment with rosiglitazone has been demonstrated to favourably modify levels of inflammatory biomarkers and adipokines, to attenuate endothelial dysfunction, and to reduce coronary events following percutaneous coronary intervention.
Diabetes and hypertension co-exist in approximately 75% of patients and this combination synergistically augments cardiovascular risk. In fact, blood pressure control seems to be of greater importance in the prevention of macrovascular disease than is glycemic control. Therefore, in patients with diabetes, dual targeting of insulin resistance and blood pressure is essential to reduce overall atherosclerotic risk. Recent evidence suggests that angiotensin receptor blockers (ARB) in addition to their antihypertensive efficacy may directly improve insulin sensitivity. These unique attributes of ARB's may prove particularly beneficial when combined with an insulin sensitizer, such as rosiglitazone, in the treatment of diabetic patients.
The rationale therefore of the ROSITEL study is to compare the effects of rosiglitazone to usual therapy on adipokine levels, inflammatory markers, and insulin sensitivity in ARB-treated diabetic patients with suboptimal glycemic control.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- rosiglitazone, metformin or sulfonylurea
- Keywords
- Type 2 Diabetes Mellitus, Thiazolidinediones, Rosiglitazone, Adipokine, Inflammation, Cardiometabolic risk, Angiotensin receptor blocker
- Medical subject headings
- Diabetes Mellitus, Type 2, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rosiglitazoneDrug
Also called Avandia
metformin or sulfonylureaDrug
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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%). Receives: Drug: metformin or sulfonylurea |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in adiponectin level in the rosiglitazone vs. metformin/sulfonylurea arms
Measured: 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
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2007 (estimated)
- Study startApr 2006
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Milan Gupta
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor-investigator, Dr. Milan Gupta, Canadian Collaborative Research Network
- Investigators
- Milan K Gupta, MD, Principal investigator, Partners Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00486187
- Sponsor's protocol ID
- AVD105195
- Status last verified
- Jan 2016
- First submitted
- 12 Jun 2007
- Last updated
- 28 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23592934
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of ROSIglitazone on Inflammatory Markers and Adipokines in Diabetic Patients Using an Angiotensin Receptor Blocker (TELmisartan) - The ROSITEL Study
- ClinicalTrials.gov ID
- NCT00486187
- Acronym / sponsor ID
- AVD105195
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Type 2 Diabetes Mellitus, Thiazolidinediones, Rosiglitazone, Adipokine, Inflammation, Cardiometabolic risk, Angiotensin receptor blocker
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Dr. Milan GuptaUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Apr 2006
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 14 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Type 2 diabetes is a chronic and progressive disease that is strongly associated with all-cause and cardiovascular mortality. The United Kingdom Prospective Diabetes Study (UKPDS) demonstrated that glycemic control alone only modestly reduces the risk of macrovascular disease among type 2 diabetic patients . Insulin resistance, which has been identified as an important underlying or associated factor in the pathogenesis of type 2 diabetes, is the main proposed mechanism responsible for the accelerated atherosclerosis noted in this population.
Evidence continues to accumulate supporting the role of chronic subclinical vascular inflammation as a central component in the development of atherosclerosis, insulin resistance and type 2 diabetes. Markers of subclinical inflammation, in particular C-reactive protein (CRP) and interleukin-6 (IL-6), have been shown to be independent predictors of both diabetes and cardiovascular risk. More recently, the visceral adipocyte has been recognized to produce a number of metabolically and hormonally active substances, collectively called adipokines. The adipokine adiponectin may have antiatherogenic and anti-inflammatory properties. High levels of adiponectin seem to be associated with protection against type 2 diabetes and atherosclerosis via anti-inflammatory pathways. Unlike adiponectin, leptin and resistin are examples of adipokines that seem to be associated with the development of both atherosclerosis and insulin resistance.
Rosiglitazone is a thiazolidinedione drug that is approved for the treatment of type 2 diabetes. As a nuclear peroxisome proliferator-activated receptor-γ agonist, rosiglitazone reduces insulin resistance, thereby sensitizing the liver, muscle, and adipose tissue to the actions of circulating insulin. Treatment with rosiglitazone has been demonstrated to favourably modify levels of inflammatory biomarkers and adipokines, to attenuate endothelial dysfunction, and to reduce coronary events following percutaneous coronary intervention.
Diabetes and hypertension co-exist in approximately 75% of patients and this combination synergistically augments cardiovascular risk. In fact, blood pressure control seems to be of greater importance in the prevention of macrovascular disease than is glycemic control. Therefore, in patients with diabetes, dual targeting of insulin resistance and blood pressure is essential to reduce overall atherosclerotic risk. Recent evidence suggests that angiotensin receptor blockers (ARB) in addition to their antihypertensive efficacy may directly improve insulin sensitivity. These unique attributes of ARB's may prove particularly beneficial when combined with an insulin sensitizer, such as rosiglitazone, in the treatment of diabetic patients.
The rationale therefore of the ROSITEL study is to compare the effects of rosiglitazone to usual therapy on adipokine levels, inflammatory markers, and insulin sensitivity in ARB-treated diabetic patients with suboptimal glycemic control.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: rosiglitazoneTreatment-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). |
| 2 | Active comparator | Drug: metformin or sulfonylureaTreatment-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%). |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
Key exclusion criteria (17 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rosiglitazoneAlso: Avandia | Drug | 1 |
| metformin or sulfonylurea | Drug | 2 |
Primary outcome
Change in adiponectin level in the rosiglitazone vs. metformin/sulfonylurea arms
Time frame: 12 weeks
1 secondary outcome
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
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2016.
- Background: PubMed 23592934Gupta 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Milan K Gupta, MD principal investigator
Partners Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rosiglitazone and metformin or sulfonylurea in people with Type 2 Diabetes Mellitus, run by Dr. Milan Gupta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in adiponectin level in the rosiglitazone vs. metformin/sulfonylurea arms (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00486187, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2016.