Reactive Oxygen Species in the Pathogenesis of Diabetic Complications

This study has been completed.
Sponsor:
Collaborators:
Juvenile Diabetes Research Foundation
Information provided by:
Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier:
NCT00703989
First received: June 23, 2008
Last updated: NA
Last verified: June 2008
History: No changes posted

June 23, 2008
June 23, 2008
February 2005
October 2006   (final data collection date for primary outcome measure)
  • intracellular advanced glycation endproducts [ Time Frame: four weeks ] [ Designated as safety issue: No ]
  • hexosamine pathway [ Time Frame: four weeks ] [ Designated as safety issue: No ]
  • prostacyclin synthase activity [ Time Frame: four weeks ] [ Designated as safety issue: No ]
Same as current
No Changes Posted
Not Provided
Not Provided
Not Provided
Not Provided
 
Reactive Oxygen Species in the Pathogenesis of Diabetic Complications
The Role of the Glucosamine Pathway and Reactive Oxygen Species in the Pathogenesis of Diabetic Complications

Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy and incipient nephropathy in these models. In cultured vascular cells, it also reduces aldose reductase gene expression, activity, and sorbitol levels. It does so by activating the enzyme transketolase. α-lipoic acid, a potent antioxidant, has also been reported to reduce both diabetic microvascular and macrovascular complications in animal models. To determine whether benfotiamine in combination with α-lipoic acid would normalize markers of ROS-induced pathways of complications in humans, we performed a pilot study in subjects with Type 1 diabetes using one daily dose of benfotiamine in combination with α-lipoic acid.

The glycemic status of study patients was assessed by measuring baseline values of HbA1c, fructosamine, and fasting plasma glucose. Mean HbA1c was 8.7+ 0.7%, mean fructosamine was 421+29 mg/dl (normal range 174-286 mg/dl), and mean fasting blood glucose was 198+44 mg/dl.

At day 0, subjects levels of markers of two benfotiamine-sensitive pathways were determined: intracellular advanced glycation endproduct (AGE) formation, as reflected by a marker of increased intracellular methylglyoxal adducts in endothelial cells, angiopoietin 2 and hexosamine pathway activity, measured by determination of N-acetylglucosamine-modified protein in circulating monocytes. PKC activity in circulating monocytes could not be measured because the amount of blood required exceeded that approved by the Committee on Clinical Investigations. Serum levels of 6-keto-PGF-1 , a stable product produced by the nonenzymatic hydration of the antiatherogenic mediator prostacyclin were also determined. Subjects then took benfotiamine 300 mg twice a day, (Advanced Orthomolecular Research, Calgary, AB,CANADA) and slow-release α-lipoic acid (600 mg twice a day) (MRI, San Francisco, CA) for 28 days. Blood was obtained at day 0, day 15, and day 28.

Data were analyzed using 1-factor analysis of variance to compare the means of all the groups. The Tukey−Kramer multiple comparisons procedure was used to determine which pairs of means were different.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Type 1 Diabetes
Dietary Supplement: benfotiamine, α-lipoic acid
benfotiamine 300 mg twice a day, (Advanced Orthomolecular Research, Calgary, AB,CANADA) and slow-release α-lipoic acid (600 mg twice a day) (MRI, San Francisco, CA) for a total duration of four weeks
Other Names:
  • benfotiamine 300 mg .slow-release
  • α-lipoic acid (600 mg twice a day)
  • Experimental: I
    Patients with Type 1 diabetes
    Intervention: Dietary Supplement: benfotiamine, α-lipoic acid
  • No Intervention: II
    Age-matched male subjects without Type 1 diabetes

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
February 2008
October 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male
  • Type 1 diabetes duration between zero and fifteen years
  • current insulin therapy

Exclusion Criteria:

  • Female
  • proliferative retinopathy
  • microalbuminuria
  • symptomatic diabetic neuropathy
  • cardiovascular disease
  • taking medications
  • smoking
Male
18 Years to 45 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00703989
CCI#: 2004-582, JDRF grant #8-2003-784, GCRC grant # MO1-RR12248
No
Michael Brownlee, M.D., Albert Einstein College of Medicien
Albert Einstein College of Medicine of Yeshiva University
  • Juvenile Diabetes Research Foundation
  • National Institutes of Health (NIH)
Principal Investigator: Michael Brownlee, M.D. Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University
June 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP