Chronic Treatment With Benfotiamine Restores Endothelial Function in People With Type 2 Diabetes Mellitus

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2007 by Ruhr University of Bochum.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Ruhr University of Bochum
ClinicalTrials.gov Identifier:
NCT00446810
First received: March 12, 2007
Last updated: September 25, 2007
Last verified: September 2007
  Purpose

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:

  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.

Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Benfotiamine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Ruhr University of Bochum:

Primary Outcome Measures:
  • Endothelial function (flow mediated dilatation - ultrasound- and reactive hyperemia- laser doppler-) [ Time Frame: September 2007- December 2008 ]

Secondary Outcome Measures:
  • Parameters of autonomic neuropathy [ Time Frame: September 2007- December 2008 ]

Estimated Enrollment: 30
Study Start Date: September 2007
Estimated Study Completion Date: December 2008
Arms Assigned Interventions
Active Comparator: A1
Benfotiamine
Drug: Benfotiamine
Active Comparator: A2 Drug: Placebo

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 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.

  Eligibility

Ages Eligible for Study:   35 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • People with type 2 diabetes mellitus
  • Age: 30-70 years

Exclusion Criteria:

  • History of myocardial infarction, stroke within the previous 6 months
  • Heart failure NYHA III or more
  • Malignant disease
  • Severe diabetes complications
  • Severe hypo- or hypertension
  • Chronic alcohol abuse
  • Renal failure (creatinine >2mg/dl)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00446810

Contacts
Contact: Alin O Stirban, PhD 0049573197 ext 3724 astirban@hdz-nrw.de
Contact: Diethelm Tschoepe, Prof. PhD 0049573197 ext 2292 dtschoepe@hdz-nrw.de

Locations
Germany
Herz- und Diabeteszentrum NRW, Georgstr. 11 Recruiting
Bad Oeynhausen, North Rhine-Westphalia, Germany, 32545
Principal Investigator: Alin O Stirban, Dr. med.         
Sponsors and Collaborators
Ruhr University of Bochum
Investigators
Study Director: Diethelm Tschoepe, Prof.PhD. Herz- und Diabeteszentrum NRW
Principal Investigator: Alin O Stirban, PhD Herz- und Diabeteszentrum NRW
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00446810     History of Changes
Other Study ID Numbers: Benfotiamine_ED_2007
Study First Received: March 12, 2007
Last Updated: September 25, 2007
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Ruhr University of Bochum:
diabetes
endothelial dysfunction
benfotiamine
postprandial
autonomic neuropathy
advanced glycation end products

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Benphothiamine
Thiamine
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on August 19, 2014