This is a single-center study that will be conducted at the University of Arizona College of Medicine, Tuscon. It is a double-blind, randomized, crossover trial design. Group A will receive the study drug followed by the placebo on the main trial day, and Group B will receive placebo first followed by the study drug. These groups will exist for both aims (both types of included patients).
Patients are randomized for the order (drug and placebo vs placebo and drug) of treatment they receive. Eligible, consented patients will present for testing from one of three locations (emergency department, inpatient ward, or home). Patients will undergo testing under the direction of trial personnel. Testing will be initiated by patients undergoing a high-resolution ultrasound for anatomic nerve assessment. Patients will then undergo a thorough sensory and motor evaluation and establish an intravenous line for blood sampling. A baseline blood sample and EDX study (prior to drug and placebo) and sensorimotor examination will be performed. These tests comprise part of a standardized array of tests performed hourly. This array of tests (serum 4AP level, EDX study, and sensorimotor examination) will be repeated every hour after treatment for three hours (Figure 1) during which the drug will have decreased to a level low enough to have no expected effect. The final hourly test is the return to baseline test. It is likely going to occur at the third hourly posttest, but is depicted separately for clarity. Only three tests after dosing will be necessary, based on our expectations from known pharmacokinetic data. Patients will then repeat this with the crossover arm (drug vs placebo).
Finally, testing is concluded at the end of this period. Research subjects will be provided a diary and asked to record symptoms as instructed. The subjects will be asked to maintain the diary for 20 weeks and the diaries will be reviewed at each follow up visit and collected at or after the final 20 week visit.
Following the initial testing, subjects will be seen for a period of 20 weeks after injury to monitor recovery and progress. Subjects will return for follow-up visits at 2, 6, 12, 18, and 20 weeks post injury. Subjects will receive a physical exam at all follow-up visit. EDX testing will be completed at 6, 12, and 18 week visits only. Subjects will complete a telephone interview at 9 and 15 weeks post injury at which time subjective motor and sensory function will be assessed by asking 1) Can you move your (affected extremity)? Yes or No 2) Can you feel your (affected extremity)? Yes or No. Review of the subject diary will also be completed. The 9, 15, and 20 week visits are not part of standard of care and are being done for research purposes only. Each visit or phone interview will last approximately 30 minutes. Subjects will be instructed to bring the research diary to their follow-up appointments and will be reviewed and evaluated by study personnel. At the final 20 week visit the diary will be collected. Additional follow up might be considered beyond standard of care for diary completion if required.