Benfotiamine in Diabetic Nephropathy - Full Text View

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:

MedlinePlus related topics: Diabetic Kidney Problems

U.S. FDA Resources

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

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:

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. Epub 2003 Feb 18.

Bakker SJ, Heine RJ, Gans RO. Thiamine may indirectly act as an antioxidant. Diabetologia. 1997 Jun;40(6):741-2. No abstract available.

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. Epub 2007 Aug 4.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2012 Jul 6.

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. Epub 2010 Apr 22.

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
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Benphothiamine
Thiamine
Adjuvants, Immunologic

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on May 22, 2013