Reactive Oxygen Species in the Pathogenesis of Diabetic Complications

November 8, 2019 updated by: Albert Einstein College of Medicine

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Bronx, New York, United States, 10461
        • GCRC, Albert Einstein College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
intracellular advanced glycation endproducts
Time Frame: four weeks
four weeks
hexosamine pathway
Time Frame: four weeks
four weeks
prostacyclin synthase activity
Time Frame: four weeks
four weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Albert Einstein College of Medicine

Collaborators

Juvenile Diabetes Research Foundation
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Michael Brownlee, M.D., Albert Einstein College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2005

Primary Completion (Actual)

October 1, 2006

Study Completion (Actual)

February 1, 2008

Study Registration Dates

First Submitted

June 23, 2008

First Submitted That Met QC Criteria

June 23, 2008

First Posted (Estimate)

June 24, 2008

Study Record Updates

Last Update Posted (Actual)

November 12, 2019

Last Update Submitted That Met QC Criteria

November 8, 2019

Last Verified

June 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2004-582
  • JDRF grant #8-2003-784
  • GCRC grant # MO1-RR12248

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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