Overt Diabetic Nephropathy, Type 2 Diabetes
Conditions
Keywords
type 2 diabetes,, glomerular filtration rate,, renal plasma flow,, endothelial dysfunction,, proteinuria,, diabetic nephropathy
Brief summary
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.
Interventions
DRUGRosiglitazone
4 mg tablets, bid, 12 months
DRUGPlacebo
2 tablets per day
Sponsors
Technische Universität Dresden
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proteinuria | at baseline and after 6 and 12 mo of treatment |
Secondary
| Measure | 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 |
Countries
Germany
Participant flow
Recruitment details
recruitment at medical clinic and outpatient department
Pre-assignment details
2 enrolled patients were excluded: one withdrew infromed consent, one developed anaphylactic reaction to sinistrin (used for renal function test)
Participants by arm
| Arm | Count |
|---|---|
| Rosiglitazone | 14 |
| Placebo | 14 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Rosiglitazone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 8 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 11 Participants |
| Age Continuous | 66.5 years STANDARD_DEVIATION 8.5 | 65.4 years STANDARD_DEVIATION 9.6 | 66.1 years STANDARD_DEVIATION 9.1 |
| Region of Enrollment Germany | 14 participants | 14 participants | 28 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 14 | 9 / 14 |
| serious Total, serious adverse events | 1 / 14 | 2 / 14 |
Outcome results
Primary
Proteinuria
Time frame: at baseline and after 6 and 12 mo of treatment
Population: per protocol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rosiglitazone | Proteinuria | baseline | 2.4 g/24hr | Standard Error 1.1 |
| Rosiglitazone | Proteinuria | 6 mo | 1.2 g/24hr | Standard Error 0.6 |
| Rosiglitazone | Proteinuria | 12 mo | 1.5 g/24hr | Standard Error 0.7 |
| Placebo | Proteinuria | baseline | 1.6 g/24hr | Standard Error 0.6 |
| Placebo | Proteinuria | 6 mo | 1.6 g/24hr | Standard Error 0.8 |
| Placebo | Proteinuria | 12 mo | 1.7 g/24hr | Standard Error 0.8 |
Secondary
Adverse Event
Time frame: every month or at occurence
Secondary
HbA1c
Time frame: at baseline and after 6 and 12 mo
Secondary
Renal Function
Time frame: at abseline and after 6 and 12 mo
Secondary
Renal Hemodynamic
Time frame: at baseline and after 6 and 12 mo of tretament