Peripheral and autonomic nerve function in 259 diabetic patients with peripheral neuropathy treated with ponalrestat (an aldose reductase inhibitor) or placebo for 18 months. United Kingdom/Scandinavian Ponalrestat Trial.
The potential of the aldose reductase inhibitor ponalrestat (600 mg daily) to ameliorate diabetic neuropathy was evaluated in 259 diabetes mellitus patients with peripheral neuropathy (defined by abnormal vibration perception threshold and abnormal peroneal motor conduction velocity) in a double-blind placebo-controlled clinical trial running for 18 months. Overall, no beneficial effect of ponalrestat on vibration perception thresholds, nerve conduction velocities, and nerve action potential amplitudes was detected. Because vibration perception thresholds and conduction velocities in median, peroneal, and sural nerves did not deteriorate in the placebo group, the potential of ponalrestat to prevent the expected deterioration in peripheral nerve function that occurs with an increased duration of diabetes was not tested. Patients with an abnormal heart rate reaction to standing (abnormal 30:15 ratio; n = 84) on ponalrestat did not deteriorate in this autonomic nerve function test as shown in those on placebo. In conclusion, ponalrestat did not improve peripheral nerve function in diabetes mellitus patients with signs of peripheral neuropathy, although it did ameliorate a deterioration in autonomic nerve function in diabetic patients with signs of autonomic neuropathy.
Sundkvist
G
G
Department of Medicine, Malmö General Hospital, Sweden.
Armstrong
F M
FM
Bradbury
J E
JE
Chaplin
C
C
Ellis
S H
SH
Owens
D R
DR
Rosén
I
I
Sönksen
P
P
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000502:physiology; D009431:Neural Conduction; D010465:Perception; D010525:Peripheral Nerves / Q000187:drug effects / Q000503:physiopathology*; D010793:Phthalazines / Q000627:therapeutic use*; D010919:Placebos; D014636:Valsalva Maneuver
D000449:Aldehyde Reductase; D006442:Glycated Hemoglobin; D010793:Phthalazines; D010919:Placebos; C042829:ponalrestat