Effects of long-term 4-aminopyridine therapy on glucose tolerance and glucokinetics in patients with spinal cord injury.

ABSTRACT

STUDY OBJECTIVE: To assess the effects of the potassium channel blocker, 4-aminopyridine, on glucose tolerance and glucokinetics in patients with spinal cord injury. DESIGN: Prospective, dose level-blinded study. SETTING: University-affiliated, tertiary-level care, Veterans Affairs medical center, and a university-affiliated research center. PATIENTS Thirty-one patients with spinal cord injury of more than 1 year's duration. INTERVENTION In a fasting state, patients ingested 75 g of glucose and completed a 5-hour oral glucose tolerance test before and after 6 months of treatment with an oral, immediate-release formulation of 4-aminopyridine. MEASUREMENTS AND MAIN RESULTS: The time course of glucose plasma concentrations during the oral glucose tolerance tests was profiled for each patient, and glucokinetic parameters were estimated. Results were compared at baseline and after 6 months of treatment with 4-aminopyridine. Of the 31 patients, 29 (94%) had impaired glucose tolerance at baseline. After 6 months of treatment with 4-aminopyridine, 12 (41%) of the 29 patients had a 2-hour postprandial glucose level that no longer supported a diagnosis of impaired glucose tolerance. No significant changes or clinically important trends were seen in fasting blood glucose concentrations or in other glucokinetic parameters in these patients. CONCLUSIONS: The long-term administration of an oral, immediate-release formulation of 4-aminopyridine to patients with longstanding spinal cord injury was associated with readily discernible, potentially clinically significant improvements in glucose tolerance. Because impaired glucose tolerance is a common finding in patients with spinal cord injury, more research, including randomized controlled trials with large study populations, is warranted on this potential treatment.