Benfotiamine in Diabetic Nephropathy

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of benfotiamine supplementation in patients with diabetic nephropathy, and to determine whether it will slow down the progression to end-stage renal disease (ESRD).

Detailed Description
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There is a worldwide increase in prevalence in type 2 diabetes mellitus, which is being paralleled by an increasing number of patients reaching dialysis because of diabetic nephropathy. Much of the fivefold increase in patients receiving dialysis treatment that occurred over the past two decades is attributable to type 2 diabetes and diabetic nephropathy. Diabetes is now the leading cause of end-stage renal disease (ESRD), with more than 40% of all new cases of ESRD occurring in patients with diabetes. Benfotiamine has been shown to reduce diabetic nephropathy and retinopathy in animal experimental models. We hypothesize that benfothiamine supplementation in patients with diabetic nephropathy will ameliorate the effects of both albuminuria/proteinuria and hyperglycaemia on oxidative stress and advanced glycation end-products (AGEs) accumulation in renal tissue, and thereby decrease inflammatory responses and fibrotic responses, causing slowing down of progression to ESRD as a consequence. Intervention: The intervention duration is 12 weeks for each group. Group A: Benfotiamine (300 mg) 3x 1 film coated tablet daily (900 mg daily dose benfotiamine) Group B: Placebo 3x 1 film coated tablet daily

Official Title
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A Double-Blind Clinical Trial of Benfotiamine Treatment in Diabetic Nephropathy

Conditions
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Diabetic Nephropathy

Intervention / Treatment
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* Drug: Benfotiamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus Patients are on treatment with angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin II antagonists (AIIA) in an unchanged dose for at least 3 months Active diabetic nephropathy as indicated by presence of microalbuminuria (15-300 mg/24 h urine) in at least two samples within 2-6 weeks in advance of inclusion in the trial HbA1c < 8.5%, a higher HbA1c < 9.5% is acceptable if the treating physician and the patient have accepted that striving for lower values is an unreachable goal (patients with high HbA1c values are the ones that one would expect to be benefit most from treatment with benfotiamine) eGFR (estimated by MDRD formula) > 30 ml/min Males and postmenopausal females Written informed consent Exclusion Criteria: Renal impairment by other causes than diabetes Stage of the disease more severe than indicated in Inclusion criteria (macroalbuminuria or renal insufficiency) Severe hypoglycemia during the last 3 months, needing help from another person Severe hepatopathy (laboratory values about three times higher than normal Endocrine disorders, e.g. hyper/hypothyroidism Blood pressure > 160/90 mmHg Severe cardiac function disturbances and severe heart rhythm disturbances Neoplasm's (excluding history of treated skin cancer of the type basal cell carcinoma BCC or squamous cell carcinoma SCC) Severe general diseases or mental disorders making the participation in the study impossible Drug abuse Female patients during pregnancy and lactation period and female patients with active menses during the past year Hypersensitivity to benfotiamine HbA1c > 9.5% Use of thiamine containing supplements during the last 3 months Participation in another study within one month before joining the benfotiamine study

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: A<br> | Drug: Benfotiamine<br>* 3x 300 mg film coated tablet daily (900 mg per day). Duration: 12 weeks.<br>* Other names: A11DA05;|
| Placebo Comparator: B<br> | Drug: Placebo<br>* 3x 1 film coated tablet daily. Duration: 12 weeks.<br>* Other names: Placebo, Wörwag Pharma GmbH & Co. KG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urinary excretion of: - Kidney injury molecule-1 (KIM-1) - Albumin |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urinary excretion of: β2 microglobulin, macrophage inhibiting factor (MIF), monocyte chemo-attractant protein-1 (MCP-1), and other advanced glycation end-products (AGEs). |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Benfotiamine, Diabetes, Nephropathy