Reactive Oxygen Species in the Pathogenesis of Diabetic Complications

Not Applicable

Completed

• Conditions: Type 1 Diabetes
• Interventions: Dietary Supplement: benfotiamine, α-lipoic acid

• Registration Number: NCT00703989
• Lead Sponsor: Albert Einstein College of Medicine

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.

Study Timeline

• Study Start: 2005-02
• Primary Completion: 2006-10
• Study Completion: 2008-02
• Status Verified: 2008-06
• Study First Submitted: 2008-06-23
• Study First Submitted QC: 2008-06-23
• Study First Posted: 2008-06-24
• Last Update Submitted: 2019-11-08
• Last Update Posted: 2019-11-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 21

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
I	benfotiamine, α-lipoic acid	Patients with Type 1 diabetes

Primary Outcome Measures

Name	Time	Method
hexosamine pathway	four weeks
prostacyclin synthase activity	four weeks
intracellular advanced glycation endproducts	four weeks

Trial Locations

Locations (1)

GCRC, Albert Einstein College of Medicine; 🇺🇸 Bronx, New York, United States