Recruiting
Phase 2

4-AP

Sponsor:

University of Arizona

Code:

NCT06003166

Conditions

Peripheral Nerve Injury

Crush Injury

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

4-Aminopyridine

Placebo

Study Details

Brief 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.

Conditions

Peripheral Nerve Injury

Crush Injury

Study ID

NCT06003166

Start date

Apr 21, 2025

Status verified date

Aug, 2025

Completion date

Jul 31, 2028

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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.
  • 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.
  • Availability for all testing days and main trial day.

Exclusion Criteria:

  • 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.

Study Design

Enrollment

68 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Diagnostic

Interventions and Outcome Measures

Arms

experimental: 4AP then placebo (Group A)

Subjects randomized to this group will receive the study drug (4AP) followed by the placebo.

experimental: Placebo then 4AP (Group B)

Subjects randomized to this group will receive the placebo first followed by the study drug (4AP)

Interventions

4-Aminopyridine

Study drug will be a one time, 10mg dose of 4-aminopyridine

Placebo

Matched placebo

Primary outcome measure

  • Subjective return of sensation [ Time Frame: During dosing of drug intervention and 2, 6, 9, 12, 15, 20 weeks post injury ]

Central Contacts and Locations

Central contacts

Andrea Horne

520-626-6456ahh@arizona.edu

Locations

Banner University Medical Center

Recruiting

Tucson, Arizona, United States, 85724

Contacts

Andrea Horne

520-626-6456ahh@arizona.edu

John Elfar, MD

5206266456elfar@arizona.edu

More Information

Sponsor

University of Arizona

Last update posted

Aug 5, 2025

Last verified

Aug, 2025

Keywords

  • 4 aminopyridine
  • peripheral nerve
  • crush injury

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Arizona on 2025-08-05.