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
  Purpose

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).


Condition Intervention Phase
Diabetic Nephropathy
Drug: Benfotiamine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind Clinical Trial of Benfotiamine Treatment in Diabetic Nephropathy

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • Change in urinary excretion of: - Kidney injury molecule-1 (KIM-1) - Albumin [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 86
Study Start Date: December 2007
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A 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
Placebo Comparator: B Drug: Placebo
3x 1 film coated tablet daily. Duration: 12 weeks.
Other Name: Placebo, Wörwag Pharma GmbH & Co. KG

Detailed Description:

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
  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00565318

Locations
Netherlands
Isala Klinieken Hospital
Zwolle, Netherlands, 8000 GK
Sponsors and Collaborators
University Medical Centre Groningen
Isala Klinieken Hospital
Wörwag Pharma GmbH & Co. KG
Predictions Network
Investigators
Study Director: G J Navis, MD, PhD University Medical Centre Groningen
Principal Investigator: H JG Bilo, MD, PhD Isala Klinieken Hospital
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alaa Alkhalaf, M.D, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT00565318     History of Changes
Other Study ID Numbers: BENFO-1, NL17390.075.07
Study First Received: November 28, 2007
Last Updated: November 13, 2009
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Centre Groningen:
Benfotiamine
Diabetes
Nephropathy

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Urologic Diseases
Benphothiamine
Thiamine
Adjuvants, Immunologic
Chelating Agents
Growth Substances
Immunologic Factors
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Sequestering Agents
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on October 21, 2014