E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic nephropathy is a serious complication of diabetes mellitus, which is the leading cause of end-stage renal disease (ESRD). Benfotiamine has been shown to reduce diabetic nephropathy and retinopathy in animal experimental models. We investigate the effect of benfotiamine supplementation in patients with diabetic nephropathy, and hypothesize that it will slow down the progression to ESRD. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate whether short-term treatment (3 months) with benfotiamine leads to a reduction in urinary excretion of β2-microglobulin and albumin. |
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E.2.2 | Secondary objectives of the trial |
To investigate whether short-term treatment (3 months) with benfotiamine leads to reduction in urinary excretion of markers of renal tubulointerstitial damage and inflammation (Kidney Injury Molecule-1, Monocyte Chemo-attractant Protein-1, Macrophage Inhibiting Factor, Complement factor C3d) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Diabetes mellitus, with onset of disease after the age of 40 years • Age: 50-70 years • 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 (30-300 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 |
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E.4 | Principal 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 (liver function enzymes 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 • 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 or other constituents of the study medication • HbA1c >9.5% • Use of vitamin B containing supplements during the last 3 months • Use of NSAIDs more than 3x per week (including self-medication) • Participation in another study within one month before joining the benfotiamine study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in urinary excretion of (measured in 24-hour urine): • β2-microglobulin • Albumin |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |