Benfotiamine in Diabetic Nephropathy

Diabetic Nephropathy Clinical Trial

— Benfo  

Official title:

A Double-Blind Clinical Trial of Benfotiamine Treatment in Diabetic Nephropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00565318
• Other study ID #: BENFO-1
• Secondary ID: NL17390.075.07
• Status: Completed
• Phase: Phase 4
• First received: November 28, 2007
• Last updated: November 13, 2009
• Start date: December 2007
• Est. completion date: June 2009

Study information

• Verified date: November 2009
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases

Intervention

Drug:
• Benfotiamine
3x 300 mg film coated tablet daily (900 mg per day). Duration: 12 weeks.
• Placebo
3x 1 film coated tablet daily. Duration: 12 weeks.

Locations

Country	Name	City	State
Netherlands	Isala Klinieken Hospital	Zwolle

Sponsors (4)

Lead Sponsor	Collaborator
University Medical Center Groningen	Isala, Predictions Network, Wörwag Pharma GmbH & Co. KG

Country where clinical trial is conducted

Netherlands, 

References & Publications (3)

Bakker SJ, Heine RJ, Gans RO. Thiamine may indirectly act as an antioxidant. Diabetologia. 1997 Jun;40(6):741-2. — View 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. Epub 2003 Feb 18. — View 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. Epub 2007 Aug 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in urinary excretion of: - Kidney injury molecule-1 (KIM-1) - Albumin		12 weeks	No
Secondary	Change in urinary excretion of: ß2 microglobulin, macrophage inhibiting factor (MIF), monocyte chemo-attractant protein-1 (MCP-1), and other advanced glycation end-products (AGEs).		12 weeks	No