-To investigate whether a short-term treatment (3 months) with benfotiamine in diabetic nephropathy patients leads to a reduction in urinary excretion of β2-microglobulin and albumin.-To investigate whether short-term treatment (3 months)…
ID
Source
Brief title
Condition
- Diabetic complications
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in urinary excretion of: (measured in 24-hour urine)
• β2-microglobulin
• Albumin
Secondary outcome
Change in urinary excretion of: (measured in 24-hour urine)
• KIM-1 (kidney injury molecule-1)
• MIF (macrophage inhibiting factor)
• MCP-1 (monocyte chemo-attractant protein-1)
• C3d
• Urinary peptidomics
• Reactive oxygen species, advanced glycation end-products (AGEs), and
carbonylated albumin
Background summary
Diabetic nephropathy is a serious complication of diabetes mellitus, which is
the leading cause of end-stage renal disease (ESRD) in the Western World.
Benfotiamine has been shown to reduce diabetic nephropathy and retinopathy in
animal experimental models. We will investigate the effect of benfotiamine
supplementation in patients with diabetic nephropathy, and hypothesize that it
will slow down the progression to ESRD if it leads to reduction of
tubulointerstitial damage and inflammation.
Study objective
-To investigate whether a short-term treatment (3 months) with benfotiamine in
diabetic nephropathy patients leads to a reduction in urinary excretion of β2-
microglobulin and albumin.
-To investigate whether short-term treatment (3 months) with benfotiamine in
diabetic nephropathy patient leads to a reduction in urinary excretion of
markers of renal tubulointerstitial damage (Kidney Injury Molecule 1, Monocyte
Chemoattractant Protein 1, Macrophage Inhibiting Factor, Complement factor C3d)
Study design
Mono-center, randomized, controlled, double-blind, parallel clinical trial
studying the effect of high dose benfotiamine compared to placebo in 66
patients with diabetic nephropathy. The study consists of two phases:
1- Run-in phase (6 weeks): In this phase patients will be instructed on
collection of 24h urine samples, it will be checked whether they have urinary
albumin excretion consistently in the microalbuminuric range, and they will be
instructed on maintenance of stable diet and activity levels prior to the study
visits to the outpatient clinic.
2- Treatment phase 1 (12 weeks): In random order, benfotiamine is given to one
half of the patients and placebo is given to the other half.
Intervention
-Treatment phase 1 (12 weeks):
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 burden and risks
-The patients are asked to attend the outpatient clinic for the study 6 times
in total. Before each visit the patients are asked to collect a 24h urine
sample. They will be asked to refrain from food from the previous evening to
take fasting blood samples (5 vials of 7 ml). In addition, a second-morning
urine sample will be collected.
-No other physical or physiological discomfort in association with
participation is anticipated than the discomfort associated with the collection
of the 24h urine samples and the blood sampling. There are no known risks
associated with the investigational product other than the rare occurrence of
urticaria and pruritus.
-Benfotiamine will be investigated to assess its effect on markers of
tubulointerstitial damage and inflammation associated with diabetic
nephropathy. If it will be demonstrated that benfotiamine causes an improvement
in these markers, the drug may become eligible for further large studies on its
efficacy in prevention of the development of end-stage renal disease in
susceptible diabetic patients. Participation of diabetic nephropathy patients
in this study is of great importance, and answering the questions of this
clinical trial is not possible without observing and analyzing the parameters
at the end of the study.
Postbus 10400
8000 GK Zwolle
NL
Postbus 10400
8000 GK Zwolle
NL
Listed location countries
Age
Inclusion criteria
• Diabetes mellitus, with onset of disease after the age of 40 years
• Age: 50-70 years
• Patients are on treatment with angiotensin converting enzyme inhibitors (ACEi) and/or angiotension II antagonists (AIIA) in an unchanged dose for at least 3 months
• Active diabetic nephropathy as indicated by presence of microalbuminuria (30-300 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 phycisian 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
• Neoplasms
• 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 or other constituents of the study medication
• HbA1c >9.5%
• Use of vitamin B containing supplements during the last 3 months
• Use of NSAIDs more than 3 times per week (including self-medication)
• Participation in another study within one month before entering the benfotiamine
study
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-001755-19-NL |
| CCMO | NL17390.075.07 |