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A Single Dose Pharmaco-Diagnostic for Peripheral Nerve Continuity After Trauma

创伤后周围神经连续性的单剂量药物诊断

基本信息

批准号：
10734303
负责人：
John Elfar
金额：
$ 38.38万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10734303
关键词：
4-Aminopyridine Affect Agreement Animals Belief Classification Clinical Clinical Trials Clinical assessments Crossover Design Data Diagnosis Diagnostic Diagnostic Imaging Dose Drug usage Esthesia FDA approved Feeling Functional disorder Hospitals Hour Human Iatrogenesis Injury Institution Institutional Review Boards Intervention Kinetics Knowledge Laboratories Left Limb structure Masks Measures Medicine Modeling Monitor Motor Vehicles Movement Multiple Sclerosis Muscle Nerve Nerve Crush Nerve Tissue Operative Surgical Procedures Oral Administration Orthopedics Outcome Pain Paralysed Participant Patients Peripheral Nerves Peripheral nerve injury Pharmaceutical Preparations Placebos Play Population Potassium Channel Procedures Prognosis Property Publishing Randomized Recording of previous events Recovery Recovery of Function Renal clearance function Resort Safety Sensorimotor functions Serum Shock Solid Stimulus Surgeon Surgical Injuries Tendon Reflex Testing Time Tissues Traction Trauma Trauma patient Withdrawal clinical prognosis dosage experience healing iatrogenic injury imaging platform improved indexing limb injury member motor control nerve injury nerve repair neuronal excitability novel pharmacologic primary outcome repaired research clinical testing response standard care standard of care tissue injury tool treatment planning ultrasound usability

项目摘要

Nerve injury can affect anyone and carries consequences that last forever, and traumatic peripheral nerve injury (TPNI) can result from settings as diverse as battlefield or motor vehicle trauma, to iatrogenic injury from surgical treatments of other serious conditions. For other tissue types, the prognosis and treatment plan are straightforward. However, when nerves fail, doctors have few tools to help guide the treatment plan and patients forever remember their experiences with pain and paralysis. If nerve injuries can happen from many causes, what is the determinant that most predicts a good outcome? The answer is nerve continuity. A nerve that has been severed, say by a bullet will never heal without surgical repair and yet, that same nerve, grazed by the bullet, or caught in the shockwave of a passing bullet, is indistinguishable from the nerve cut by the bullet. Both nerves do not work, and yet the latter, unsevered nerve is best left to recover on its own without surgery. Two types of nerve injury exist, both yield nerves that are equally dysfunctional and yet we need to surgically repair one whereas surgery is detrimental to the other. No test exists to tell these nerves apart until weeks have passed after the injury. After weeks have passed, we use electrodiagnostics (EDX) to tell which nerves were severed. This is the state of the art in TPNI diagnosis. Because continuity of the nerve is itself impossible to define for weeks after injury, the current standard treatment is waiting for spontaneous recovery in most patients we guess do not have a severed nerve. In every field of medicine, there are nerve injuries monitored in this way - without tools for definitive diagnosis, based on our clinical suspicion. We recently discovered that a current, FDA-approved drug (4-aminopyridine, 4AP), has the previously unknown effect of immediately allowing diagnosis of traumatically paralyzed nerves. Small doses can distinguish the severed nerve, which requires immediate surgery, from the non-severed nerve, which can be safely monitored. This novel property of 4AP, a drug already used in humans may be explored while we wait for function to spontaneously return. Based on our preliminary data, we intend to repurpose 4AP to diagnose nerve discontinuity instead of just guessing if the nerve is severed and hoping for recovery. We want to try 4AP in patients who have nerve injury where we cannot tell if the nerve was severed or not. We obtained FDA approval for a trial of 4AP in humans to investigate nerve continuity and have modified our institutional IRB approval to proceed. We want to test 4AP in humans with TPNI in a novel way: As a pharmacologic diagnostic, where the results of a challenge with the drug reveal something about the underlying nerve continuity. With the knowledge gained from this trial, we hope to provide solid information that can confirm or refute clinical guesswork on the critical issue of nerve continuity.

神经损伤可以影响任何人，并带来永久的后果，以及创伤性外周