4-Aminopyridine for Nerve Injury

Recruiting at 2 trial locations

Overseen By Andrea Horne

Age: 18+

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: John Elfar

Must not be taking: Aminopyridines

Disqualifiers: Seizures, Multiple sclerosis, Stroke, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

70 Participants Needed

Trial Summary

What is the purpose of this trial?

To evaluate the role of 4-aminopyridine (4-AP) on the course of recovery after peripheral nerve traction and/or crush injury. This study aims to test the hypothesis that 4-aminopyridine speeds the often slow and unpredictable recovery after peripheral nerve traction and/or crush injuries.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot use any other aminopyridine medications.

What evidence supports the effectiveness of the drug 4-Aminopyridine for nerve injury?

Research shows that 4-Aminopyridine can improve nerve function and recovery after nerve injuries in mice by enhancing myelination (the protective covering of nerves), increasing muscle strength, and reducing nerve damage. It has also been used to help with symptoms in multiple sclerosis, suggesting its potential in improving nerve-related conditions. ^{1 2 3 4 5}

Is 4-Aminopyridine generally safe for humans?

4-Aminopyridine is used in humans for conditions like multiple sclerosis and has been shown to improve nerve function. However, it can cause side effects such as tremors, excitability, and convulsions due to its effects on the central nervous system. ^{1 2 3 4 5}

How does the drug 4-Aminopyridine differ from other treatments for nerve injury?

4-Aminopyridine (4-AP) is unique because it can be used both as a treatment and a diagnostic tool for nerve injuries, helping to differentiate between types of nerve damage. Unlike other treatments, 4-AP enhances nerve function by improving myelination (the protective covering of nerves) and nerve conduction, and it can be administered orally, transdermally (through the skin), or by injection. ^{1 2 3 4 6}

Research Team

John Elfar, MD

Principal Investigator

University of Arizona

Benjamin Lee, MD

Principal Investigator

University of Arizona

Eligibility Criteria

Men aged 45-75 with early-stage, non-metastatic prostate cancer scheduled for nerve-sparing prostate surgery. They must have a PSA level under 15 ng/ml, no history of recurrent or advanced prostate cancer, and not need postoperative therapy. Participants should be sexually active with an erectile function score of at least 17 and cannot use other treatments for erectile dysfunction until three months after surgery.

Inclusion Criteria

I have been sexually active regularly for the last 6 months and in the 12 weeks before my prostate biopsy or surgery.

I am willing and able to give my consent to participate.

I am a man with early-stage prostate cancer planning to have a specific prostate surgery.

Exclusion Criteria

I am scheduled for additional treatment after surgery for prostate cancer due to its advanced stage or spread.

My prostate cancer has spread beyond the prostate.

I am not taking any aminopyridine medications for any condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 4-aminopyridine or placebo daily for 2 months post-surgery

8 weeks

Daily self-administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Weekly assessments

Long-term follow-up

Participants continue to be monitored for long-term outcomes

1 year

Treatment Details

Interventions

• 4-Aminopyridine

Trial Overview The trial is testing if the drug 4-aminopyridine can speed up recovery from nerve damage caused by traction or crush injuries during prostate surgery. Patients will either receive the actual drug or a placebo to compare outcomes.

Participant Groups

Group I: Group A: Investigational Treatment Experimental Treatment 1 Intervention

* FDA-approved 10mg dalfampridine (generic Ampyra) * Subjects will not take more than 2 tablets in a 24-hour period * Subjects will take the tablets whole. They will not break, crush, chew, or dissolve tablets before swallowing. * The subjects will be told that the medication is released slowly over time and if the tablet is broken, the medicine may be released too fast which can raise the chance of having a seizure. * Study drug can be taken with or without food. * If a dose is missed they should not make up the missed dose. They will be told not to take two doses at the same time but to take the next dose at the regular scheduled time. * Subjects will be reminded not to take study drug together with other aminopyridine medications, including compounded 4-AP (sometimes called 4-aminopyridine or fampridine).

Group II: Group B: Placebo Placebo Group 1 Intervention

Subjects will receive an oral dose of placebo treatment the day after surgery, continuing daily for 2 months (60 days) following the same administration instructions as the investigational treatment. The placebo tablets will be manufactured by a licensed compounding pharmacy. The Investigational Drug Service at Banner University Medical Center will manage the placebos.

Who Is Running the Clinical Trial?

John Elfar

Lead Sponsor

Trials

4

Recruited

500+

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

University of Arizona

Collaborator

Trials

545

Recruited

161,000+

Milton S. Hershey Medical Center

Collaborator

Trials

515

Recruited

2,873,000+

Findings from Research

4-Aminopyridine (4-AP) significantly improves motor function and enhances recovery after traumatic peripheral nerve injuries in mice, regardless of whether it is administered orally or through injection.

Chronic daily treatment with 4-AP leads to better myelination, increased muscle mass, and improved muscle force, indicating its potential as an effective therapy for nerve injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human equivalent dose of oral 4-aminopyridine differentiates nerve crush injury from transection injury and improves post-injury function in mice. Hsu, CG., Talukder, MAH., Yue, L., et al.[2020]

Transdermal administration of 4-aminopyridine (TD-4-AP) significantly enhances functional recovery and nerve conduction after traumatic peripheral nerve injury in mice, showing promise as a treatment method.

Chronic treatment with TD-4-AP leads to fewer degenerating axons and thicker myelin sheaths compared to controls, indicating its potential to promote nerve repair and improve motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal delivery of 4-aminopyridine accelerates motor functional recovery and improves nerve morphology following sciatic nerve crush injury in mice. Clark, AR., Hsu, CG., Talukder, MAH., et al.[2021]

In a study involving 20 subjects (10 in the 4-AP-treated group and 10 in the control group), 4-aminopyridine (4-AP) significantly reduced clinical scores of experimental autoimmune neuritis (EAN), indicating its potential effectiveness in treating this condition.

The 4-AP-treated group also showed improved motor conductance velocity without causing any pathological changes, suggesting that it may be a safe therapeutic option for demyelinating neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

4-Aminopyridine ameliorates experimental autoimmune neuritis in Lewis rats. Moriguchi, K., Miyamoto, K., Kusunoki, S.[2018]

4-aminopyridine (4-AP) has shown potential as a diagnostic tool for differentiating traumatic peripheral nerve injuries (TPNIs) based on axonal continuity, as it restored muscle responses in rats with crush injuries but not in those with transection injuries.

In a study involving anesthetized rats, both systemic and local administration of 4-AP significantly improved muscle response to electrical stimulation after crush injuries, indicating its efficacy in cases where nerve continuity is maintained.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

4-Aminopyridine: A Single-Dose Diagnostic Agent to Differentiate Axonal Continuity in Nerve Injuries. Gurjar, AA., Manto, KM., Estrada, JA., et al.[2022]

References

1. India pubmed.ncbi.nlm.nih.gov

Human equivalent dose of oral 4-aminopyridine differentiates nerve crush injury from transection injury and improves post-injury function in mice. [2020]

2. India pubmed.ncbi.nlm.nih.gov

Transdermal delivery of 4-aminopyridine accelerates motor functional recovery and improves nerve morphology following sciatic nerve crush injury in mice. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

4-Aminopyridine ameliorates experimental autoimmune neuritis in Lewis rats. [2018]

4. England pubmed.ncbi.nlm.nih.gov

4-Aminopyridine: A Single-Dose Diagnostic Agent to Differentiate Axonal Continuity in Nerve Injuries. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

4-aminopyridine-a review. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

The effects of 4-aminopyridine and methylprednisolone on recovery of the facial nerve crush injury. [2021]