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
  Purpose

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.


Condition Intervention
Type 1 Diabetes
Dietary Supplement: benfotiamine, α-lipoic acid

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Role of the Glucosamine Pathway and Reactive Oxygen Species in the Pathogenesis of Diabetic Complications

Resource links provided by NLM:


Further study details as provided by Albert Einstein College of Medicine of Yeshiva University:

Primary Outcome Measures:
  • 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 ]

Enrollment: 21
Study Start Date: February 2005
Study Completion Date: February 2008
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I
Patients with 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)
No Intervention: II
Age-matched male subjects without Type 1 diabetes

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  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: NCT00703989

Locations
United States, New York
GCRC, Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Sponsors and Collaborators
Albert Einstein College of Medicine of Yeshiva University
Juvenile Diabetes Research Foundation
Investigators
Principal Investigator: Michael Brownlee, M.D. Albert Einstein College of Medicine of Yeshiva University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Michael Brownlee, M.D., Albert Einstein College of Medicien
ClinicalTrials.gov Identifier: NCT00703989     History of Changes
Other Study ID Numbers: CCI#: 2004-582, JDRF grant #8-2003-784, GCRC grant # MO1-RR12248
Study First Received: June 23, 2008
Last Updated: June 23, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by Albert Einstein College of Medicine of Yeshiva University:
hyperglycemia
diabetic complications
advanced glycation endproducts
hexosamine pathway
prostacyclin synthase
reactive oxygen species

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Complications
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Thioctic Acid
Thiamine
Benphothiamine
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Adjuvants, Immunologic
Immunologic Factors
Chelating Agents

ClinicalTrials.gov processed this record on July 22, 2014