Benfotiamine in Diabetic Nephropathy

This study has been completed.
Sponsor:
Collaborators:
Isala Klinieken Hospital
Wörwag Pharma GmbH & Co. KG
Predictions Network
Information provided by:
University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT00565318
First received: November 28, 2007
Last updated: November 13, 2009
Last verified: November 2009

November 28, 2007
November 13, 2009
December 2007
June 2009   (final data collection date for primary outcome measure)
Change in urinary excretion of: - Kidney injury molecule-1 (KIM-1) - Albumin [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Change in urinary excretion of: -β2 microglobulin -Albumin [ Time Frame: 12 weeks ]
Complete list of historical versions of study NCT00565318 on ClinicalTrials.gov Archive Site
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). [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Change in urinary excretion of: kidney injury molecule-1 (KIM-1), macrophage inhibiting factor (MIF), monocyte chemo-attractant protein-1 (MCP-1), and other advanced glycation end-products (AGEs). [ Time Frame: 12 weeks ]
Not Provided
Not Provided
 
Benfotiamine in Diabetic Nephropathy
A Double-Blind Clinical Trial of Benfotiamine Treatment in Diabetic Nephropathy

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).

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
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Diabetic Nephropathy
  • Drug: Benfotiamine
    3x 300 mg film coated tablet daily (900 mg per day). Duration: 12 weeks.
    Other Names:
    • Milgamma® mono 300, Wörwag Pharma GmbH & Co. KG
    • A11DA05
  • Drug: Placebo
    3x 1 film coated tablet daily. Duration: 12 weeks.
    Other Name: Placebo, Wörwag Pharma GmbH & Co. KG
  • Active Comparator: A
    Intervention: Drug: Benfotiamine
  • Placebo Comparator: B
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
86
June 2009
June 2009   (final data collection date for primary outcome measure)

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
Both
40 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00565318
BENFO-1, NL17390.075.07
No
Alaa Alkhalaf, M.D, University Medical Center Groningen
University Medical Centre Groningen
  • Isala Klinieken Hospital
  • Wörwag Pharma GmbH & Co. KG
  • Predictions Network
Study Director: G J Navis, MD, PhD University Medical Centre Groningen
Principal Investigator: H JG Bilo, MD, PhD Isala Klinieken Hospital
University Medical Centre Groningen
November 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP