- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00565318
Benfotiamine in Diabetic Nephropathy (Benfo)
A Double-Blind Clinical Trial of Benfotiamine Treatment in Diabetic Nephropathy
Study Overview
Status
Conditions
Intervention / Treatment
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
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Locations
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-
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Zwolle, Netherlands, 8000 GK
- Isala Klinieken Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: A
|
3x 300 mg film coated tablet daily (900 mg per day).
Duration: 12 weeks.
Other Names:
|
Placebo Comparator: B
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3x 1 film coated tablet daily.
Duration: 12 weeks.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in urinary excretion of: - Kidney injury molecule-1 (KIM-1) - Albumin
Time Frame: 12 weeks
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
12 weeks
|
Collaborators and Investigators
Investigators
- Study Director: G J Navis, MD, PhD, University Medical Center Groningen
- Principal Investigator: H JG Bilo, MD, PhD, Isala
Publications and helpful links
General 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. doi: 10.1038/nm834. 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. doi: 10.1007/s00125-007-0771-4. Epub 2007 Aug 4.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BENFO-1
- NL17390.075.07
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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