Ignite Creation Date:
2024-05-05 @ 5:24 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00446810
Status:
UNKNOWN
Last Update Posted:
2007-09-27
First Post:
2007-03-12
Brief Title:
Chronic Treatment With Benfotiamine Restores Endothelial Function in People With Type 2 Diabetes Mellitus
Sponsor:
Ruhr University of Bochum
Organization:
Ruhr University of Bochum
Study Overview
Official Title:
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
Status:
UNKNOWN
Status Verified Date:
2007-09
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
An AGE-rich diet can induce after 2-6 weeks persistent increases in mediators linked to vascular dysfunction eg 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 mgday for 6 weeks in people with type 2 diabetes mellitus
1 prevents postprandial impairment of endothelial function after a high-AGE meal
2 Improves fasting endothelial function
3 Improves parameters of autonomic function in fasting and postprandial state
4 Improves insulin sensitivity and prevents postprandial increase in insulin resistance
The hypotheses of this study are that chronical treatment with benfotiamine 900 mgday for 6 weeks in people with type 2 diabetes mellitus
1 prevents postprandial impairment of endothelial function after a high-AGE meal
2 Improves fasting endothelial function
3 Improves parameters of autonomic function in fasting and postprandial state
4 Improves insulin sensitivity and prevents postprandial increase in insulin resistance
Detailed Description:
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 Estatins 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 mgday 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 24 and 6 hours postprandially
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 Estatins 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 mgday 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 24 and 6 hours postprandially
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None