Ignite Creation Date:
2025-12-25 @ 12:31 AM
Ignite Modification Date:
2025-12-28 @ 10:34 PM
Study NCT ID:
NCT00490867
Status:
COMPLETED
Last Update Posted:
2018-03-20
First Post:
2007-06-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effect of Long Term α-Lipoic Acid Treatment on Endothelial Function in Patients With Type 2 Diabetes
Sponsor:
Medical University of Vienna
Organization:
Study Overview
Official Title:
Effect of Long Term α-Lipoic Acid Treatment on Endothelial Function in Patients With Type 2 Diabetes
Status:
COMPLETED
Status Verified Date:
2007-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In the present study, endothelium dependent vasodilation will be induced by administration of acetylcholine (ACh). To ascertain whether the vascular effects, if any, of α-lipoic acid are limited to the endothelium, endothelium independent vasodilation will also be assessed by administration of glyceroltrinitrate (GTN).
Study objectives To investigate the effect of α-lipoic acid therapy on endothelium dependent and independent vasodilation, assessed by forearm blood flow (FBF), in patients with type 2 diabetes mellitus
Study design
Randomized, double-blinded, parallel group study for 23 days:
Day 1: FBF responses to acetylcholine and glyceroltrinitrate Day 2-22: intravenous infusion of 600 mg α-lipoic acid or placebo Day 23: FBF responses to acetylcholine and glyceroltrinitrate
Study population 30 subjects with type 2 diabetes
Study medication Acetylcholine (ACh) - intraarterial infusion, 25, 50, 100 nmol/min, infusion period 3 minutes/dose level Glyceroltrinitrate (GTN) - intraarterial infusion, 4, 8, 16 nmol/min, infusion period 3 minutes/dose level α-lipoic acid - intravenous infusion of 600 mg in 250 ml saline solution over 30 minutes
Main outcome variables Forearm blood flow (Ratio between intervention and control arm) Additional outcome variables Arterial blood pressure, pulse rate, markers of inflammation and oxidative stress, Insulin plasma levels, Glucose plasma levels
Risk/benefit assessment The insertion of intravenous cannula may cause mild and transient pain. A minor hematoma may occur at the site of cannula insertion. The insertion of the intraarterial cannula is performed under local anaesthesia and causes mild pain. The meassurement of forearm bloodflow, espacialy the wrist cuff (\>200 mmHG) may be uncomfortably. Local administration of drugs through a needle in the brachial artery allows the study of direct vascular effects of the drugs. Drug doses are 100 to 1000 times lower than a systemic effective dose, therefore no systemic adverse events are expected. There is experience in brachial artery infusions at our institution, and it is considered a safe technique. α-lipoic acid was well tolerated in healthy volunteers and subjects with diabetes at doses up to 600 mg intravenously and 1800 mg orally with side effects comparable with placebo. Altogether 50 ml blood will be collected throughout the study.
Study objectives To investigate the effect of α-lipoic acid therapy on endothelium dependent and independent vasodilation, assessed by forearm blood flow (FBF), in patients with type 2 diabetes mellitus
Study design
Randomized, double-blinded, parallel group study for 23 days:
Day 1: FBF responses to acetylcholine and glyceroltrinitrate Day 2-22: intravenous infusion of 600 mg α-lipoic acid or placebo Day 23: FBF responses to acetylcholine and glyceroltrinitrate
Study population 30 subjects with type 2 diabetes
Study medication Acetylcholine (ACh) - intraarterial infusion, 25, 50, 100 nmol/min, infusion period 3 minutes/dose level Glyceroltrinitrate (GTN) - intraarterial infusion, 4, 8, 16 nmol/min, infusion period 3 minutes/dose level α-lipoic acid - intravenous infusion of 600 mg in 250 ml saline solution over 30 minutes
Main outcome variables Forearm blood flow (Ratio between intervention and control arm) Additional outcome variables Arterial blood pressure, pulse rate, markers of inflammation and oxidative stress, Insulin plasma levels, Glucose plasma levels
Risk/benefit assessment The insertion of intravenous cannula may cause mild and transient pain. A minor hematoma may occur at the site of cannula insertion. The insertion of the intraarterial cannula is performed under local anaesthesia and causes mild pain. The meassurement of forearm bloodflow, espacialy the wrist cuff (\>200 mmHG) may be uncomfortably. Local administration of drugs through a needle in the brachial artery allows the study of direct vascular effects of the drugs. Drug doses are 100 to 1000 times lower than a systemic effective dose, therefore no systemic adverse events are expected. There is experience in brachial artery infusions at our institution, and it is considered a safe technique. α-lipoic acid was well tolerated in healthy volunteers and subjects with diabetes at doses up to 600 mg intravenously and 1800 mg orally with side effects comparable with placebo. Altogether 50 ml blood will be collected throughout the study.
Detailed Description:
Background
Type 2 (non-insulin-dependent) diabetes is associated with a marked increase in the risk of cardiovascular disease. Before overt cardiovascular disease occurs, impairment of vascular endothelial function is detectable. Endothelium-dependent vasodilation is impaired in patients with type 2 diabetes, indicating that diabetes is associated with endothelial dysfunction. Recently, formation of reactive oxygen species (ROS) has been linked to diabetes. These heterogeneous group of highly reactive compounds interact with NO and thereby inhibit vasodilation caused by NO. Formation of ROS is therefore thought to be an important mechanism by which type 2 diabetes induces endothelial dysfunction. α-Lipoic acid, which has been used for the treatment of diabetic neuropathy, was shown to have antioxidant capacities in vitro and animal experiments. Short term treatment with intraarterial α-lipoic acid was shown to improve endothelium dependent vasodilation in type 2 diabetics. However, to date, no data exists about the long term effcts of α-lipoic acid on vascular function in type 2 diabetics. In the present study, endothelium dependent vasodilation will be induced by administration of acetylcholine (ACh). To ascertain whether the vascular effects, if any, of α-lipoic acid are limited to the endothelium, endothelium independent vasodilation will also be assessed by administration of glyceroltrinitrate (GTN).
Study objectives To investigate the effect of α-lipoic acid therapy on endothelium dependent and independent vasodilation, assessed by forearm blood flow (FBF), in patients with type 2 diabetes mellitus
Study design
Randomized, double-blinded, parallel group study for 23 days:
Day 1: FBF responses to acetylcholine and glyceroltrinitrate Day 2-22: intravenous infusion of 600 mg α-lipoic acid or placebo Day 23: FBF responses to acetylcholine and glyceroltrinitrate
Study population 30 subjects with type 2 diabetes
Study medication Acetylcholine (ACh) - intraarterial infusion, 25, 50, 100 nmol/min, infusion period 3 minutes/dose level Glyceroltrinitrate (GTN) - intraarterial infusion, 4, 8, 16 nmol/min, infusion period 3 minutes/dose level α-lipoic acid - intravenous infusion of 600 mg in 250 ml saline solution over 30 minutes
Main outcome variables Forearm blood flow (Ratio between intervention and control arm) Additional outcome variables Arterial blood pressure, pulse rate, markers of inflammation and oxidative stress, Insulin plasma levels, Glucose plasma levels
Risk/benefit assessment The insertion of intravenous cannula may cause mild and transient pain. A minor hematoma may occur at the site of cannula insertion. The insertion of the intraarterial cannula is performed under local anaesthesia and causes mild pain. The meassurement of forearm bloodflow, espacialy the wrist cuff (\>200 mmHG) may be uncomfortably. Local administration of drugs through a needle in the brachial artery allows the study of direct vascular effects of the drugs. Drug doses are 100 to 1000 times lower than a systemic effective dose, therefore no systemic adverse events are expected. There is experience in brachial artery infusions at our institution, and it is considered a safe technique. α-lipoic acid was well tolerated in healthy volunteers and subjects with diabetes at doses up to 600 mg intravenously and 1800 mg orally with side effects comparable with placebo. Altogether 50 ml blood will be collected throughout the study.
Type 2 (non-insulin-dependent) diabetes is associated with a marked increase in the risk of cardiovascular disease. Before overt cardiovascular disease occurs, impairment of vascular endothelial function is detectable. Endothelium-dependent vasodilation is impaired in patients with type 2 diabetes, indicating that diabetes is associated with endothelial dysfunction. Recently, formation of reactive oxygen species (ROS) has been linked to diabetes. These heterogeneous group of highly reactive compounds interact with NO and thereby inhibit vasodilation caused by NO. Formation of ROS is therefore thought to be an important mechanism by which type 2 diabetes induces endothelial dysfunction. α-Lipoic acid, which has been used for the treatment of diabetic neuropathy, was shown to have antioxidant capacities in vitro and animal experiments. Short term treatment with intraarterial α-lipoic acid was shown to improve endothelium dependent vasodilation in type 2 diabetics. However, to date, no data exists about the long term effcts of α-lipoic acid on vascular function in type 2 diabetics. In the present study, endothelium dependent vasodilation will be induced by administration of acetylcholine (ACh). To ascertain whether the vascular effects, if any, of α-lipoic acid are limited to the endothelium, endothelium independent vasodilation will also be assessed by administration of glyceroltrinitrate (GTN).
Study objectives To investigate the effect of α-lipoic acid therapy on endothelium dependent and independent vasodilation, assessed by forearm blood flow (FBF), in patients with type 2 diabetes mellitus
Study design
Randomized, double-blinded, parallel group study for 23 days:
Day 1: FBF responses to acetylcholine and glyceroltrinitrate Day 2-22: intravenous infusion of 600 mg α-lipoic acid or placebo Day 23: FBF responses to acetylcholine and glyceroltrinitrate
Study population 30 subjects with type 2 diabetes
Study medication Acetylcholine (ACh) - intraarterial infusion, 25, 50, 100 nmol/min, infusion period 3 minutes/dose level Glyceroltrinitrate (GTN) - intraarterial infusion, 4, 8, 16 nmol/min, infusion period 3 minutes/dose level α-lipoic acid - intravenous infusion of 600 mg in 250 ml saline solution over 30 minutes
Main outcome variables Forearm blood flow (Ratio between intervention and control arm) Additional outcome variables Arterial blood pressure, pulse rate, markers of inflammation and oxidative stress, Insulin plasma levels, Glucose plasma levels
Risk/benefit assessment The insertion of intravenous cannula may cause mild and transient pain. A minor hematoma may occur at the site of cannula insertion. The insertion of the intraarterial cannula is performed under local anaesthesia and causes mild pain. The meassurement of forearm bloodflow, espacialy the wrist cuff (\>200 mmHG) may be uncomfortably. Local administration of drugs through a needle in the brachial artery allows the study of direct vascular effects of the drugs. Drug doses are 100 to 1000 times lower than a systemic effective dose, therefore no systemic adverse events are expected. There is experience in brachial artery infusions at our institution, and it is considered a safe technique. α-lipoic acid was well tolerated in healthy volunteers and subjects with diabetes at doses up to 600 mg intravenously and 1800 mg orally with side effects comparable with placebo. Altogether 50 ml blood will be collected throughout the study.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: