4-AP Peripheral Nerve Crossover Trial

• Status: Not yet recruiting
• Trial end date: 2028-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the role of single dose 4-aminopyridine (4-AP) on the diagnosis of severing vs non-severing nerve injury after peripheral nerve traction and/or crush injury. The investigational treatment will be used to test the hypothesis that 4-aminopyridine can speed the determination of nerve continuity after peripheral nerve traction and/or crush injuries allowing the identification of incomplete injuries earlier than standard electrodiagnostic (EDX) and clinical assessment.

Participants will be randomized to one of two groups to determine the order of treatment they receive (drug and placebo vs placebo and drug). Participants will undergo baseline testing for nerve assessment, receive either drug or placebo based on randomization and undergo hourly sensory and motor evaluation, EDX testing and serum 4AP levels for three hours after dosing. Participants will then repeat this with the crossover arm.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Arizona
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Treatments: 4-Aminopyridine

Criteria

Inclusion Criteria:

• Patients with trauma involving two or less limbs where the continuity of a given peripheral nerve or nerves is unclear on presenting physical examination.

• Closed soft tissue envelope obscuring direct observation of the continuity of the affected nerve.

• Cognitive ability to report sensory and motor deficit during examination.

• Able to complete single day dosing within seven days (168 hours) of nerve injury diagnosis.

• Eligible for standard of care plan of monitoring vs surgical exploration of the nerve.

• Adults subject aged 18-90

• Known limb trauma which resulted in nerve injury (aim 1) or post-operative/post intervention nerve injury (aim 2).

• Ability to give written informed consent.

• Capable of safely undergoing electrodiagnostic testing (EDX).

• Availability for all testing days and main trial day.

Exclusion Criteria:

• Not able to complete dosing within seven days (168 hours) of nerve injury diagnosis

• Distracting injury which prevents adequate examination.

• Plan for surgical exploration of the nerve during the ensuing 48 hours.

• Plan for surgical exploration of the nerve as part of another surgical procedure within 48 hours of evaluation.

• Intoxication during examination or evidence of cognitive deficit that emerges during examination.

• History of multiple sclerosis, stroke or any other diagnosed neurological disorder

• History of hypersensitivity to AMPYRA® or 4-aminopyridine

• Current use of aminopyridine medications, including other compounded 4-AP

• Renal impairment based on calculated GFR (GFR<80 mL/min). This laboratory value is measured in all inpatient trauma patients as part of the standard of care.

• History of difficult compliance with timely follow up or plan to seek care at another institution closer to home.

• Patients outside the age range or unable to consent.

• Patients with a known history of a seizure disorder (4AP overdose can, in selected cases, result in limited seizure activity).

• Patients with a concomitant traumatic brain injury.

• Patients unable to communicate return or loss of sensation.

• Patients unable to exhibit motor control on the affected limb at baseline.

• Patients unwilling to complete the study requirements.

• Patients with injuries too extensive to isolate a single nerve(s) for testing.

• Patients currently taking organic cat-ion transporter 2 (OCT2) inhibitors, e.g. Cimetidine.

• Pregnancy, breastfeeding or incarcerated individuals.