4-AP Peripheral Nerve Crossover Trial

NCT06003166 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 00002665R01NS111293
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

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

Keywords

4 aminopyridine; peripheral nerve; crush injury

Outcome Measures

Primary Outcomes (1)

• Subjective return of sensation

  Return of lost sensation after nerve injury attributable to circulating 4AP. Subjective return of sensation in the injured limb or portion of the limb. Patients for this trial are not able to sense in portions of their limbs. The measure will be sensation, measured on the binary scale of yes or no (able to feel the extremity versus unable to feel). This is assessed through clinical examination of the injured limb.

  During dosing of drug intervention and 2, 6, 9, 12, 15, 20 weeks post injury

Study Arms (2)

4AP then placebo (Group A)

EXPERIMENTAL

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

Drug: 4-Aminopyridine; Other: Placebo

Placebo then 4AP (Group B)

EXPERIMENTAL

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

Drug: 4-Aminopyridine; Other: Placebo

Interventions

4-Aminopyridine DRUG

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

Also known as: 4AP

4AP then placebo (Group A); Placebo then 4AP (Group B)

Placebo OTHER

Matched placebo

4AP then placebo (Group A); Placebo then 4AP (Group B)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Arizona: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Banner University Medical Center

Tucson, Arizona, 85724, United States

RECRUITING

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MeSH Terms

Conditions

Peripheral Nerve Injuries; Crush Injuries

Interventions

4-Aminopyridine

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• John Elfar, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Horne

CONTACT

520-626-6456; ahh@arizona.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Tenured Professor, Chairman, Department of Orthopaedic Surgery

Study Record Dates

• First Submitted: August 9, 2023
• First Posted: August 21, 2023
• Study Start: April 21, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): July 31, 2028
• Last Updated: August 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)