Clinical trial NCT01109212: The Effects of Bindarit in Diabetic Nephropathy
Official title: The Effects of the Association Bindarit + Irbesartan Versus Irbesartan Alone on Albuminuria on Patients With Diabetic Nephropathy. Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Nephropathy
Keywords: Type 2-Diabetic Nephrophaty
bindarit
albuminuria
MCP-1
Lead sponsor: Aziende Chimiche Riunite Angelini Francesco S.p.A
Sponsor class: INDUSTRY
Collaborators: name: Mario Negri Institute for Pharmacological Research
First posted: 2010-04-23
Enrollment: 100
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Urinary Albumin Excretion (µg/min) levels in the overnight urine specimen.
timeFrame: 12 weeks
Secondary outcomes:
measure: Urinary Monocyte Chemoattractant protein (MCP-1/CCL2)(pg/ml) levels in the overnight urine specimen.
timeFrame: 12 weeks
measure: Serum lipids
timeFrame: 12 weeks
measure: Safety and tolerability of bindarit in association of irbesartan.
timeFrame: 12 weeks
measure: Albuminuria remission rates
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Ranica
country: Italy
facility: The Mario Negri Institute for Pharmacological Research- Clinical Research Center for Rare Diseases
state: Bergamo
city: Treviglio
country: Italy
facility: Azienda Ospedaliera di Treviglio-Caravaggio - Unità Operativa Malattie Metaboliche e Diabetologia
state: Bergamo
city: Bergamo
country: Italy
facility: Azienda Ospedaliera OO.RR. Bergamo - Unità Operativa Diabetologia
city: Milano
country: Italy
facility: IRCCS Fondazione Centro S. Raffaele del Monte Tabor- Unità Operativa Medicina Generale
city: Sassari
country: Italy
facility: Ist. Patologia Medica e metodologia Clinica - Università di Sassari
city: Ljubljana
country: Slovenia
facility: University Medical Center Dpt Endocrinology Diabetes and Metabolic Diseases- Diabetology Unit
Study officials:
affiliation: Mario Negri Institute for Pharmacological Research
name: Giuseppe Remuzzi, PhD
role: PRINCIPAL_INVESTIGATOR
References: