Peripheral Nerve InjuryPhase 2NCT06003166
4-AP Peripheral Nerve Crossover Trial
A Phase 2 study testing 4-Aminopyridine in people with Peripheral Nerve Injury and Crush Injury, run by University of Arizona at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Peripheral Nerve Injury, Crush Injury
- What is being tested?
- 4-Aminopyridine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2025to 31 Jul 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 18Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Banner University Medical Center
Tucson, Arizona, 85724
Andrea Horne, 520-626-6456, ahh@arizona.edu
John Elfar, MD, 5206266456, elfar@arizona.edu
About this study
Official title: Pharmaco-Diagnostic Crossover Trial for Peripheral Nerve Continuity After Trauma
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.
Read the detailed description
This is a single-center study that will be conducted at the University of Arizona College of Medicine, Tucson. It is a double-blind, randomized, crossover trial design. Group A will receive the study drug followed by the placebo on the main trial day, and Group B will receive placebo first followed by the study drug. These groups will exist for both aims (both types of included patients).
Patients are randomized for the order (drug and placebo vs placebo and drug) of treatment they receive. Eligible, consented patients will present for testing from one of three locations (emergency department, inpatient ward, or home). Patients will undergo testing under the direction of trial personnel. Patients will undergo a thorough baseline sensory and motor evaluation and establish an intravenous line for blood sampling. A baseline blood sample (prior to drug and placebo) will be performed. These tests comprise part of a standardized array of tests performed hourly. This array of tests (serum 4AP level and sensorimotor examination) will be repeated every hour after treatment for three hours during which the drug will have decreased to a level low enough to have no expected effect. The final hourly test is the return to baseline test. It is likely going to occur at the third hourly post-test, but is depicted separately for clarity. Only three tests after dosing will be necessary, based on our expectations from known pharmacokinetic data. Patients will then repeat this with the crossover arm (drug vs placebo). Testing is concluded at the end of this period.
Following the initial testing, subjects will be seen for a period of 20 weeks after injury to monitor recovery and progress. Subjects will return for follow-up visits at 2, 6, 12, 18, and 20 weeks post injury. Subjects will receive a physical exam at all follow-up visit. Subjects will complete a telephone interview at 9 and 15 weeks post injury at which time subjective motor and sensory function will be assessed by asking 1) Can you move your (affected extremity)? Yes or No 2) Can you feel your (affected extremity)? Yes or No. Review of the subject diary will also be completed. The 9, 15, and 20 week visits are not part of standard of care and are being done for research purposes only. Each visit or phone interview will last approximately 30 minutes.
- Conditions
- Peripheral Nerve Injury, Crush Injury
- Being tested
- 4-Aminopyridine, Placebo
- Keywords
- 4 aminopyridine, peripheral nerve, crush injury
- Medical subject headings
- Peripheral Nerve Injuries, Crush Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4-AminopyridineDrug
Also called 4AP
Study drug will be a one time, 10mg dose of 4-aminopyridine
PlaceboOther
Matched placebo
| Study group | Role | What they receive |
|---|---|---|
| 4AP then placebo (Group A) | Experimental | Subjects randomized to this group will receive the study drug (4AP) followed by the placebo. Receives: 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) Receives: Drug: 4-Aminopyridine; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During dosing of drug intervention and 2, 6, 9, 12, 15, 20 weeks post injury
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2023
- Study start21 Apr 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (38)Papers the sponsor has linked to this study.
- Other trials for Peripheral Nerve InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, John Elfar, University of Arizona
- Investigators
- John Elfar, MD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06003166
- Sponsor's protocol ID
- 00002665
- Other IDs
- R01NS111293
- Status last verified
- Aug 2025
- First submitted
- 9 Aug 2023
- Last updated
- 5 Aug 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Robinson LR. Role of neurophysiologic evaluation in diagnosis. J Am Acad Orthop Surg. 2000 May-Jun;8(3):190-9. doi: 10.5435/00124635-200005000-00006.
PubMed 10874226Robinson LR. Traumatic injury to peripheral nerves. Muscle Nerve. 2000 Jun;23(6):863-73. doi: 10.1002/(sici)1097-4598(200006)23:63.0.co;2-0.
PubMed 10842261Lerner A, Soudry M. Armed Conflict Injuries to the Extremities: A Treatment Manual. Springer Science & Business Media; 2011.
Lundborg G. Nerve Injury and Repair: Regeneration, Reconstruction, and Cortical Remodeling. Elsevier/Churchill Livingstone; 2005.
Brushart TM. Nerve Repair. Oxford University Press; 2011.
Mackinnon SE, Dellon AL. Surgery of the Peripheral Nerve. Thieme Medical Publishers; 1988.
Birch R. Surgical Disorders of the Peripheral Nerves. Springer London; 2011.
Wilbourn AJ. The electrodiagnostic examination with peripheral nerve injuries. Clin Plast Surg. 2003 Apr;30(2):139-54. doi: 10.1016/s0094-1298(02)00099-8.
PubMed 12737349Seddon HJ, Medawar PB, Smith H. Rate of regeneration of peripheral nerves in man. J Physiol. 1943 Sep 30;102(2):191-215. doi: 10.1113/jphysiol.1943.sp004027. No abstract available.
PubMed 16991601SEDDON HJ. Nerve grafting. Ann R Coll Surg Engl. 1963 May;32(5):269-80. No abstract available.
PubMed 13987582SUNDERLAND S, BRADLEY KC. Denervation atrophy of the distal stump of a severed nerve. J Comp Neurol. 1950 Dec;93(3):401-9. doi: 10.1002/cne.900930304. No abstract available.
PubMed 14803568SUNDERLAND S. A classification of peripheral nerve injuries producing loss of function. Brain. 1951 Dec;74(4):491-516. doi: 10.1093/brain/74.4.491. No abstract available.
PubMed 14895767Sir SS. Nerves And Nerve Injuries. Churchill Livingstone; 1978
Grass G, Kabir K, Ohse J, Rangger C, Besch L, Mathiak G. Primary Exploration of Radial Nerve is Not Required for Radial Nerve Palsy while Treating Humerus Shaft Fractures with Unreamed Humerus Nails (UHN). Open Orthop J. 2011;5:319-23. doi: 10.2174/1874325001105010319. Epub 2011 Aug 26.
PubMed 21915231Korompilias AV, Lykissas MG, Kostas-Agnantis IP, Vekris MD, Soucacos PN, Beris AE. Approach to radial nerve palsy caused by humerus shaft fracture: is primary exploration necessary? Injury. 2013 Mar;44(3):323-6. doi: 10.1016/j.injury.2013.01.004. Epub 2013 Jan 23.
PubMed 23352153
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmaco-Diagnostic Crossover Trial for Peripheral Nerve Continuity After Trauma
- ClinicalTrials.gov ID
- NCT06003166
- Acronym / sponsor ID
- 00002665
- Conditions
- Peripheral Nerve Injury, Crush Injury
- Keywords
- 4 aminopyridine, peripheral nerve, crush injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 21 Apr 2025 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Jul 2028 (estimated)
- First posted
- 21 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a single-center study that will be conducted at the University of Arizona College of Medicine, Tucson. It is a double-blind, randomized, crossover trial design. Group A will receive the study drug followed by the placebo on the main trial day, and Group B will receive placebo first followed by the study drug. These groups will exist for both aims (both types of included patients).
Patients are randomized for the order (drug and placebo vs placebo and drug) of treatment they receive. Eligible, consented patients will present for testing from one of three locations (emergency department, inpatient ward, or home). Patients will undergo testing under the direction of trial personnel. Patients will undergo a thorough baseline sensory and motor evaluation and establish an intravenous line for blood sampling. A baseline blood sample (prior to drug and placebo) will be performed. These tests comprise part of a standardized array of tests performed hourly. This array of tests (serum 4AP level and sensorimotor examination) will be repeated every hour after treatment for three hours during which the drug will have decreased to a level low enough to have no expected effect. The final hourly test is the return to baseline test. It is likely going to occur at the third hourly post-test, but is depicted separately for clarity. Only three tests after dosing will be necessary, based on our expectations from known pharmacokinetic data. Patients will then repeat this with the crossover arm (drug vs placebo). Testing is concluded at the end of this period.
Following the initial testing, subjects will be seen for a period of 20 weeks after injury to monitor recovery and progress. Subjects will return for follow-up visits at 2, 6, 12, 18, and 20 weeks post injury. Subjects will receive a physical exam at all follow-up visit. Subjects will complete a telephone interview at 9 and 15 weeks post injury at which time subjective motor and sensory function will be assessed by asking 1) Can you move your (affected extremity)? Yes or No 2) Can you feel your (affected extremity)? Yes or No. Review of the subject diary will also be completed. The 9, 15, and 20 week visits are not part of standard of care and are being done for research purposes only. Each visit or phone interview will last approximately 30 minutes.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 4AP then placebo (Group A) | Experimental | Drug: 4-Aminopyridine, Other: PlaceboSubjects randomized to this group will receive the study drug (4AP) followed by the placebo. |
| Placebo then 4AP (Group B) | Experimental | Drug: 4-Aminopyridine, Other: PlaceboSubjects randomized to this group will receive the placebo first followed by the study drug (4AP) |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4-AminopyridineAlso: 4APStudy drug will be a one time, 10mg dose of 4-aminopyridine | Drug | 4AP then placebo (Group A), Placebo then 4AP (Group B) |
| PlaceboMatched placebo | Other | 4AP then placebo (Group A), Placebo then 4AP (Group B) |
Primary outcome
Subjective return of sensation
Time frame: During dosing of drug intervention and 2, 6, 9, 12, 15, 20 weeks post injury
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2025.
- Background: PubMed 10874226Robinson LR. Role of neurophysiologic evaluation in diagnosis. J Am Acad Orthop Surg. 2000 May-Jun;8(3):190-9. doi: 10.5435/00124635-200005000-00006.
- Background: PubMed 10842261Robinson LR. Traumatic injury to peripheral nerves. Muscle Nerve. 2000 Jun;23(6):863-73. doi: 10.1002/(sici)1097-4598(200006)23:63.0.co;2-0.
- BackgroundLerner A, Soudry M. Armed Conflict Injuries to the Extremities: A Treatment Manual. Springer Science & Business Media; 2011.
- BackgroundLundborg G. Nerve Injury and Repair: Regeneration, Reconstruction, and Cortical Remodeling. Elsevier/Churchill Livingstone; 2005.
- BackgroundBrushart TM. Nerve Repair. Oxford University Press; 2011.
- BackgroundMackinnon SE, Dellon AL. Surgery of the Peripheral Nerve. Thieme Medical Publishers; 1988.
- BackgroundBirch R. Surgical Disorders of the Peripheral Nerves. Springer London; 2011.
- Background: PubMed 12737349Wilbourn AJ. The electrodiagnostic examination with peripheral nerve injuries. Clin Plast Surg. 2003 Apr;30(2):139-54. doi: 10.1016/s0094-1298(02)00099-8.
- Background: PubMed 16991601Seddon HJ, Medawar PB, Smith H. Rate of regeneration of peripheral nerves in man. J Physiol. 1943 Sep 30;102(2):191-215. doi: 10.1113/jphysiol.1943.sp004027. No abstract available.
- Background: PubMed 13987582SEDDON HJ. Nerve grafting. Ann R Coll Surg Engl. 1963 May;32(5):269-80. No abstract available.
- Background: PubMed 14803568SUNDERLAND S, BRADLEY KC. Denervation atrophy of the distal stump of a severed nerve. J Comp Neurol. 1950 Dec;93(3):401-9. doi: 10.1002/cne.900930304. No abstract available.
- Background: PubMed 14895767SUNDERLAND S. A classification of peripheral nerve injuries producing loss of function. Brain. 1951 Dec;74(4):491-516. doi: 10.1093/brain/74.4.491. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
John Elfar, MD principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 4-Aminopyridine in people with Peripheral Nerve Injury and Crush Injury, run by University of Arizona at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andrea Horne (520-626-6456, ahh@arizona.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Subjective return of sensation (time frame: During dosing of drug intervention and 2, 6, 9, 12, 15, 20 weeks post injury). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06003166, which also lists 38 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2025.