Diabetic Nephropathy
Conditions
Keywords
Type 2-Diabetic Nephrophaty, bindarit, albuminuria, MCP-1
Brief summary
The purpose of this study is to determine whether bindarit is effective to reduce albuminuria, compared to placebo, in nephropathic patients treated with irbesartan, as a background therapy.
Detailed description
This is a pilot phase II, double-blind, multicentre, randomized, placebo-controlled, parallel groups study in patients with DN undergoing irbesartan therapy. According to screening urinary albumin excretion, at baseline and before randomization, all patients will be categorized into 2 strata: Stratum 1: microalbuminuria (20 to 200 μg/min, in at least 2 of 3 consecutive overnight urine samples collected at the screening) Stratum 2: macroalbuminuria (\>200 μg/min, in at least 2 of 3 consecutive overnight urine samples collected at the screening). Within each stratum, patients will be randomly allocated on a 1:1 basis to the 2 treatment arms (after one month induction period): * bindarit 600MG twice a day * placebo All patients will be treated with irbesartan 300 mg/day as background therapy. After 12 months of treatment albuminuria will be evaluated as primary endopoint.
Interventions
DRUGBindarit
dosage form:tablet dosage:2x300 mg frequency:b.i.d duration:12 weeks
DRUGPlacebo
dosage form: tablet dosage: n.a. frequency: 2xplacebo b.i.d duration:12 weeks
Sponsors
Mario Negri Institute for Pharmacological Research
Aziende Chimiche Riunite Angelini Francesco S.p.A
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* male and female patients with no limitation of race, aged 30 to 70 years; * Type 2 diabetes defined as: \> 30 years of age at diagnosis; insulin not required within 6 months of initial diagnosis; no history of diabetic ketoacidosis; currently treated with diet, oral hypoglycemics or insulin \[Brenner 2000\]; * microalbuminuria defined as urinary albumin excretion, 20 to 200 µg/min in at least 2 of 3 overnight urine samples or macroalbuminuria defined as urinary albumin excretion, \> 200 µg/min in at least 2 of 3 overnight urine samples, confirmed in the baseline collection; should baseline albuminuria data not to be available, the patient may be conditionally treated; * glycosylated haemoglobin (Hb A1c) \<12% at Screening \[Brenner 2000\]; * serum creatinine ≤ 3 mg/dL at Screening; * normotensive patients or hypertensive patients on stable antihypertensive therapy over the last 3 months and without specific contraindications to angiotensin antagonist therapy; * female patients of childbearing potential required to have a negative pregnancy test and use an approved birth control method; * patients legally able to give written informed consent to the trial (signed and dated by the patient).
Exclusion criteria
Patients cannot enter the trial under the following circumstances: * patients hypersensitive or allergic to ARBs or bindarit or its components, or with a positive history for drug allergy; * Type 1 diabetes \[Brenner 2000\]; * history of non diabetic renal disease, including renal artery stenosis \[Brenner 2000\]; * history of heart failure before enrolment \[Brenner 2000\]; * acute myocardial infarction, coronary artery bypass grafting within the past one month \[Brenner 2000\]; * cerebral vascular accident or coronary angioplasty within the past six months month \[Brenner 2000\]; * Transient Ischemic Attacks (TIA) in the past 12 months \[Brenner 2000\]; * primary aldosteronism or pheocromocytoma \[Brenner 2000\]; * severe uncontrolled hypertension (sitting diastolic blood pressure \> 115 and/or sitting systolic blood pressure\> 220 mm Hg) in the previous 6 months; * chronic use of corticosteroids, non-steroidal anti-inflammatory drugs, immunosuppressive drugs, MAO inhibitors; * patients under the influence of alcohol or narcotics; * patients treated with experimental drugs in the previous 4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Albumin Excretion (µg/min) levels in the overnight urine specimen. | 12 weeks | Relative change (per cent change) in Urinary Albumin Excretion (UAE) from the baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Monocyte Chemoattractant protein (MCP-1/CCL2)(pg/ml) levels in the overnight urine specimen. | 12 weeks | Relative change (per cent change) in Urinary MCP-1 levels from the baseline. |
| Serum lipids | 12 weeks | Relative change (per cent change) in total cholesterol, cholesterol HDL, triglycerides, apolipoprotein-A, apolipoprotein-B from the baseline. |
| Safety and tolerability of bindarit in association of irbesartan. | 12 weeks | Changes in anthropometrics, laboratory parameters and vital signs from the baseline. Number of adverse events. |
| Albuminuria remission rates | 12 weeks | Rate of remission from macro to microalbuminuria and from micro to normoalbuminuria. |
Countries
Italy, Slovenia
Outcome results
None listed