Chronic Treatment With Benfotiamine Restores Endothelial Function in People With Type 2 Diabetes Mellitus
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|ClinicalTrials.gov Identifier: NCT00446810|
Recruitment Status : Unknown
Verified September 2007 by Ruhr University of Bochum.
Recruitment status was: Recruiting
First Posted : March 13, 2007
Last Update Posted : September 27, 2007
|First Submitted Date ICMJE||March 12, 2007|
|First Posted Date ICMJE||March 13, 2007|
|Last Update Posted Date||September 27, 2007|
|Study Start Date ICMJE||September 2007|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Endothelial function (flow mediated dilatation - ultrasound- and reactive hyperemia- laser doppler-) [ Time Frame: September 2007- December 2008 ]|
|Original Primary Outcome Measures ICMJE
||Endothelial function (flow mediated dilatation - ultrasound- and reactive hyperemia- laser doppler-)|
|Change History||Complete list of historical versions of study NCT00446810 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Parameters of autonomic neuropathy [ Time Frame: September 2007- December 2008 ]|
|Original Secondary Outcome Measures ICMJE
||Parameters of autonomic neuropathy|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Chronic Treatment With Benfotiamine Restores Endothelial Function in People With Type 2 Diabetes Mellitus|
|Official Title ICMJE||Effects of a Chronical Treatment With Benfotiamine in People With Type 2 Diabetes Mellitus on Pre- and Postprandial Endothelial Function, as Well as on the Function of the Autonomic Nervous System|
An AGE-rich diet can induce after 2-6 weeks persistent increases in mediators linked to vascular dysfunction (e.g. TNFα, VCAM-1) in people with type 2 diabetes mellitus (T2DM). Benfotiamine (BT), the liposoluble derivative of vitamin B1, blocks several pathways common to hyperglycaemia- and AGE-induced endothelial dysfunction. We have shown that advanced glycation end products (AGE) of a regular mixed meal can acutely induce vascular dysfunction in T2DM and that this effects can be prevented by a three days pretreatment with BT.
The hypotheses of this study are that chronical treatment with benfotiamine (900 mg/day for 6 weeks) in people with type 2 diabetes mellitus:
People with type 2 diabetes mellitus (T2DM) have a two to fivefold increase in cardiovascular mortality compared to non-diabetic controls.
Endothelial dysfunction (ED) is an early messenger of atherosclerosis and is responsible for increased vascular permeability, platelet aggregation and adhesion, leucocyte adhesion and smooth muscle cell proliferation and favours a vasoconstrictive and pro-inflammatory state.
Postprandial ED occurs not only in patients with CV disease or diabetes, but even in healthy subjects. Distinctive and cumulative effects of hyperglycemia and hypertriglyceridemia on postprandial ED have been demonstrated. Since postprandial dysmetabolism was linked to CV disease, the postprandial ED was proposed to be the mechanism connecting them. Considering that the postprandial state covers most of our daytime, interventions targeting a reduction in postprandial ED might play a decisive role in atherosclerosis prevention.
For the treatment of postprandial ED several therapeutical approaches have been suggested, such as treatment with folic acid, tetrahydrobiopterin, vitamins C and E,statins etc.
These approaches aim at reducing postprandial oxidative stress (vitamins C and E, statins and partly folic acid), postprandial hyperglycemia (insulin), postprandial hypertriglyceridemia (statins) or have a direct effect on endothelial NO production (folic acid, insulin and tetrahydrobiopterin).
Recent data suggests that advanced glycation endproducts (AGE) might also play a role in the development of ED, leading to the long-term complications of diabetes and accelerated aging. AGEs are a heterogeneous group of moieties, one of the most representative being carboxymethyllysine (CML). Diet is a major source of exogenous AGEs and the food AGE content is highly dependent on food nutrient composition, as well as on temperature, method and duration of heat application during cooking. About 10% of ingested AGEs are rapidly absorbed and partly retained into the body, where they exert different pathological effects including binding with and activation of receptors for AGE (RAGE). AGE precursors such as methylglyoxal (MG) can also activate RAGE. Endogenous MG synthesis increases in parallel with hyperglycemia in vivo. Postprandially, the absorbed and endogenously generated AGEs and MG act synergistically to decrease vascular function through direct NO scavenging or increased oxidative stress. Part of these effects can be counteracted by benfotiamine (BT), a liposoluble vitamin B1 derivative with much higher bioavailability than thiamine. BT, commonly used in the treatment of diabetic neuropathy, is a transketolase activator that directs glucose substrates to the pentose phosphate pathway. Thus, it blocks several hyperglycemia-induced pathways, one of them being endogenous AGE and dicarbonyls formation. We have recently shown that a three day pretreatment with benfotiamine can prevent postprandial ED in T2DM (Stirban et al, Diabetes Care, 2006).
This study aims at investigating the effects of a chronical treatment with benfotiamine (900 mg/day for 6 weeks) on parameters of endothelial function and autonomic neuropathy in fasting and postprandial state in people with T2DM.
We will therefore investigate 30 people with type 2 diabetes mellitus in a randomized, cross-over, double blind, placebo-controlled design. Pre- and postprandial endothelial dysfunction (flow mediated dilatation -ultrasound- and reactive hyperemia -laser-doppler-) will be investigated before and after chronical treatment with benfotiamine. Investigations will be performed in fasting state as well as 2,4 and 6 hours postprandially.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
|Condition ICMJE||Diabetes Mellitus, Type 2|
|Publications *||Stirban A, Negrean M, Stratmann B, Gawlowski T, Horstmann T, Götting C, Kleesiek K, Mueller-Roesel M, Koschinsky T, Uribarri J, Vlassara H, Tschoepe D. Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care. 2006 Sep;29(9):2064-71.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Estimated Enrollment ICMJE
|Original Enrollment ICMJE||Same as current|
|Estimated Study Completion Date||December 2008|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||35 Years to 70 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Germany|
|Removed Location Countries|
|NCT Number ICMJE||NCT00446810|
|Other Study ID Numbers ICMJE||Benfotiamine_ED_2007|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Ruhr University of Bochum|
|Collaborators ICMJE||Not Provided|
|PRS Account||Ruhr University of Bochum|
|Verification Date||September 2007|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP