Effects of Rosiglitazone on Renal Hemodynamics and Proteinuria of Type 2 Diabetic Patients With Renal Insufficiency Due to Overt Diabetic Nephropathy

Study Overview
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Brief Summary
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Objective: To evaluate how rosiglitazone does influence the renal plasma flow, the glomerular filtration rate and the degree of proteinuria in type 2 diabetic patients with renal insufficiency due to overt diabetic nephropathy. Background: Diabetic nephropathy is a world wide public health concern of increasing proportions. It has become the most common single cause of end-stage renal disease in the United States and in Europe. Previous studies have already found agents modifying the renin-angiotensin-system (ACE inhibitors and angiotensin receptor blocker) to retard diabetic nephropathy. These agents are likely to exert multiple effects in the kidney. One of them appear to be their known ability to improve endothelial function and to change renal glomerular hemodynamics. In a previous study we demonstrated an improvement of renal endothelial dysfunction in type 2 diabetic patients without end organ damage after treatment with rosiglitazone. In that study, rosiglitazone significantly reduced glomerular hyperfiltration. This was associated with a reduction of urinary albumin excretion. The observed effects are potentially important in the context of renal protection, provided that a similar beneficial effect of rosiglitazone is demonstrable in overt diabetic nephropathy (renal insufficiency, hypertension, proteinuria). Hypothesis Rosiglitazone decreases proteinuria and improves renal hemodynamic function in patients with chronic renal insufficiency due to overt diabetic nephropathy.

Official Title
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Effects of Rosiglitazone on Renal Hemodynamics and Proteinuria of Type 2 Diabetic Patients With Renal Insufficiency Due to Overt Diabetic Nephropathy

Conditions
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Type 2 Diabetes, Overt Diabetic Nephropathy

Intervention / Treatment
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* Drug: Rosiglitazone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type 2 diabetes mellitus -age between 40 and 75 years -well controlled HbA1c (< 7.5%) -chronic renal failure (creatinin clearance between 70 and 30 mL/(min x 1.73 m²) according to the Cockroft equation) -proteinuria > 300 mg / 24 hours Exclusion Criteria: type 1 diabetes -poorly controlled type 2 diabetes (HbA1c > 7.5%) or unstable blood glucose during the day (capillary blood glucose self monitoring) -elevation of ALT, AST or GGT more than 2.5 fold the upper normal value -CHF (more than grade 1 of NYHA) -uncontrolled hypertension -malignant tumorous disorder -hyper- or hypothyroidism -pregnant women -nursing women

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rosiglitazone<br> | Drug: Rosiglitazone<br>* 4 mg tablets, bid, 12 months<br>|
| Placebo Comparator: placebo<br> | Drug: Placebo<br>* 2 tablets per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proteinuria |  | at baseline and after 6 and 12 mo of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Hemodynamic |  | at baseline and after 6 and 12 mo of tretament | 
| Renal Function |  | at abseline and after 6 and 12 mo | 
| Adverse Event |  | every month or at occurence | 
| HbA1c |  | at baseline and after 6 and 12 mo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes,, glomerular filtration rate,, renal plasma flow,, endothelial dysfunction,, proteinuria,, diabetic nephropathy