A Single Dose Pharmaco-Diagnostic for Peripheral Nerve Continuity After Trauma
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 1
- Locations
- 1
- Primary Endpoint
- Subjective Return of Sensation
Study Overview
Brief Summary
The purpose of this study is to evaluate the role of 4-aminopyridine (4-AP) on the course of recovery after peripheral nerve traction and/or crush injury. The investigational treatment will be used to test the hypothesis that 4-aminopyridine speeds the often slow and unpredictable recovery after peripheral nerve traction and/or crush injuries.
Detailed Description
This proposal contains two distinct aims to be investigated in two similar but distinct groups of patients.
Aim 1: To examine the mechanistic effect of 4AP on the return of sensorimotor function and EDX sensitivity in the setting of nerve dysfunction from orthopaedic trauma. This aim tests the hypothesis that oral one-time administration of 4AP provides transient return of function and EDX sensitivity to the traumatically denervated limb in alert patients with known limb injuries not involving the central nervous system.
Aim 2: To examine the mechanistic effect of 4AP on the return of sensorimotor function and EDX sensitivity in the setting of iatrogenic nerve injury after surgical intervention. This aim tests the identical hypothesis as in Aim 1 in a distinct group of patients, whose nerve dysfunction is the result of a clinical intervention, and whose function before that intervention was intact.
Scientific Background and Gaps
Neurological injury in the form of traction or crush to nerves that control muscles and sensory function is common. Because an understanding of these injuries is only now beginning to emerge, research on potential treatments is an important next step. Through experiments performed on animals with the Acorda Therapeutics, Inc. version of the drug (AMPYRA®), 4-aminopyridine (4-AP) has been strikingly effective in ameliorating the effect of a standardized peripheral nerve crush injury. The peripheral nerve injury used in the experiments was a standard model of peripheral nerve injury used to measure recovery in animals and is a model of peripheral nerve traction and crush injury that has been studied for over thirty years. The investigators have found that:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Diagnostic
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 dosing within four days (96 hours) of nerve injury diagnosis.
- •Able to provide informed consent
- •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 four days (96 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
- •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.
- •Pregnancy, breastfeeding or incarcerated individuals.
- •Patients currently taking organic cat-ion transporter 2 (OCT2) inhibitors, eg. Cimetidine.
Arms & Interventions
Single dose 4AP
15mm opaque capsule containing 10mg of 4-AP
Intervention: 4-Aminopyridine (Drug)
Placebo
Opaque capsule identical looking to the 4AP placebo pill
Intervention: Placebo oral tablet (Drug)
Outcomes
Primary Outcomes
Subjective Return of Sensation
Time Frame: During dosing of drug intervention (5 hours) and 2, 6, 9, 12, 15, 20 weeks post injury
Return of lost sensation after nerve injury attributable to circulating 4-AP. 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.
Secondary Outcomes
No secondary outcomes reported