Reactive Oxygen Species in the Pathogenesis of Diabetic Complications
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
benfotiamine, α-lipoic acid
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring hyperglycemia, diabetic complications, advanced glycation endproducts, hexosamine pathway, prostacyclin synthase, reactive oxygen species
Eligibility 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
Sites / Locations
- GCRC, Albert Einstein College of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
I
II
Arm Description
Patients with Type 1 diabetes
Age-matched male subjects without Type 1 diabetes
Outcomes
Primary Outcome Measures
intracellular advanced glycation endproducts
hexosamine pathway
prostacyclin synthase activity
Secondary Outcome Measures
Full Information
NCT ID
NCT00703989
First Posted
June 23, 2008
Last Updated
November 8, 2019
Sponsor
Albert Einstein College of Medicine
Collaborators
Juvenile Diabetes Research Foundation, National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT00703989
Brief Title
Reactive Oxygen Species in the Pathogenesis of Diabetic Complications
Official Title
The Role of the Glucosamine Pathway and Reactive Oxygen Species in the Pathogenesis of Diabetic Complications
Study Type
Interventional
2. Study Status
Record Verification Date
June 2008
Overall Recruitment Status
Completed
Study Start Date
February 2005 (undefined)
Primary Completion Date
October 2006 (Actual)
Study Completion Date
February 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Albert Einstein College of Medicine
Collaborators
Juvenile Diabetes Research Foundation, National Institutes of Health (NIH)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
hyperglycemia, diabetic complications, advanced glycation endproducts, hexosamine pathway, prostacyclin synthase, reactive oxygen species
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
I
Arm Type
Experimental
Arm Description
Patients with Type 1 diabetes
Arm Title
II
Arm Type
No Intervention
Arm Description
Age-matched male subjects without Type 1 diabetes
Intervention Type
Dietary Supplement
Intervention Name(s)
benfotiamine, α-lipoic acid
Other Intervention Name(s)
benfotiamine 300 mg .slow-release, α-lipoic acid (600 mg twice a day)
Intervention Description
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
Primary Outcome Measure Information:
Title
intracellular advanced glycation endproducts
Time Frame
four weeks
Title
hexosamine pathway
Time Frame
four weeks
Title
prostacyclin synthase activity
Time Frame
four weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Brownlee, M.D.
Organizational Affiliation
Albert Einstein College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
GCRC, Albert Einstein College of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
15919781
Citation
Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005 Jun;54(6):1615-25. doi: 10.2337/diabetes.54.6.1615. No abstract available.
Results Reference
background
PubMed Identifier
18663426
Citation
Du X, Edelstein D, Brownlee M. Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes. Diabetologia. 2008 Oct;51(10):1930-2. doi: 10.1007/s00125-008-1100-2. Epub 2008 Jul 29.
Results Reference
derived
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Reactive Oxygen Species in the Pathogenesis of Diabetic Complications
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