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Benfotiamine in Diabetic Nephropathy (Benfo)

Primary Purpose

Diabetic Nephropathy

Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Benfotiamine
Placebo
Sponsored by
University Medical Center Groningen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Nephropathy focused on measuring Benfotiamine, Diabetes, Nephropathy

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Isala Klinieken Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

A

B

Arm Description

Outcomes

Primary Outcome Measures

Change in urinary excretion of: - Kidney injury molecule-1 (KIM-1) - Albumin

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).

Full Information

First Posted
November 28, 2007
Last Updated
November 13, 2009
Sponsor
University Medical Center Groningen
Collaborators
Isala, Wörwag Pharma GmbH & Co. KG, Predictions Network
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1. Study Identification

Unique Protocol Identification Number
NCT00565318
Brief Title
Benfotiamine in Diabetic Nephropathy
Acronym
Benfo
Official Title
A Double-Blind Clinical Trial of Benfotiamine Treatment in Diabetic Nephropathy
Study Type
Interventional

2. Study Status

Record Verification Date
November 2009
Overall Recruitment Status
Completed
Study Start Date
December 2007 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
June 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University Medical Center Groningen
Collaborators
Isala, Wörwag Pharma GmbH & Co. KG, Predictions Network

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Nephropathy
Keywords
Benfotiamine, Diabetes, Nephropathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
86 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Active Comparator
Arm Title
B
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Benfotiamine
Other Intervention Name(s)
Milgamma® mono 300, Wörwag Pharma GmbH & Co. KG, A11DA05
Intervention Description
3x 300 mg film coated tablet daily (900 mg per day). Duration: 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo, Wörwag Pharma GmbH & Co. KG
Intervention Description
3x 1 film coated tablet daily. Duration: 12 weeks.
Primary Outcome Measure Information:
Title
Change in urinary excretion of: - Kidney injury molecule-1 (KIM-1) - Albumin
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
G J Navis, MD, PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
H JG Bilo, MD, PhD
Organizational Affiliation
Isala
Official's Role
Principal Investigator
Facility Information:
Facility Name
Isala Klinieken Hospital
City
Zwolle
ZIP/Postal Code
8000 GK
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
12592403
Citation
Hammes HP, Du X, Edelstein D, Taguchi T, Matsumura T, Ju Q, Lin J, Bierhaus A, Nawroth P, Hannak D, Neumaier M, Bergfeld R, Giardino I, Brownlee M. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med. 2003 Mar;9(3):294-9. doi: 10.1038/nm834. Epub 2003 Feb 18.
Results Reference
background
PubMed Identifier
9222658
Citation
Bakker SJ, Heine RJ, Gans RO. Thiamine may indirectly act as an antioxidant. Diabetologia. 1997 Jun;40(6):741-2. No abstract available.
Results Reference
background
PubMed Identifier
17676306
Citation
Thornalley PJ, Babaei-Jadidi R, Al Ali H, Rabbani N, Antonysunil A, Larkin J, Ahmed A, Rayman G, Bodmer CW. High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease. Diabetologia. 2007 Oct;50(10):2164-70. doi: 10.1007/s00125-007-0771-4. Epub 2007 Aug 4.
Results Reference
background
PubMed Identifier
22792314
Citation
Alkhalaf A, Kleefstra N, Groenier KH, Bilo HJ, Gans RO, Heeringa P, Scheijen JL, Schalkwijk CG, Navis GJ, Bakker SJ. Effect of benfotiamine on advanced glycation endproducts and markers of endothelial dysfunction and inflammation in diabetic nephropathy. PLoS One. 2012;7(7):e40427. doi: 10.1371/journal.pone.0040427. Epub 2012 Jul 6.
Results Reference
derived
PubMed Identifier
20413516
Citation
Alkhalaf A, Klooster A, van Oeveren W, Achenbach U, Kleefstra N, Slingerland RJ, Mijnhout GS, Bilo HJ, Gans RO, Navis GJ, Bakker SJ. A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy. Diabetes Care. 2010 Jul;33(7):1598-601. doi: 10.2337/dc09-2241. Epub 2010 Apr 22.
Results Reference
derived

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Benfotiamine in Diabetic Nephropathy

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