Effect of Long Term α-Lipoic Acid Treatment on Endothelial Function in Patients With Type 2 Diabetes
Status:
Completed
Trial end date:
2007-08-01
Target enrollment:
Participant gender:
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.