4-Aminopyridine for Nerve Injury

Recruiting at 2 trial locations

Overseen By Edward Messing, MD

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug 4-aminopyridine can speed up recovery after certain nerve injuries, specifically those caused by stretching or crushing. Participants will receive either the medication or a placebo to determine if the drug accelerates and stabilizes recovery. Men with prostate cancer confined to the organ, planning to undergo a specific type of prostate surgery, might be suitable candidates, particularly if they have been sexually active recently and are willing to delay erectile dysfunction treatments post-surgery. As a Phase 2, Phase 3 trial, this study measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to significant medical advancements.

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.

Is there any evidence suggesting that 4-aminopyridine is likely to be safe for humans?

Research has shown that 4-aminopyridine, also known as dalfampridine, is generally safe for people with multiple sclerosis (MS) over time. Studies indicate that the treatment is usually well-tolerated at the recommended dose of 10 mg twice a day.

Common side effects in MS patients include urinary tract infections, dizziness, and trouble sleeping, occurring more often than with a placebo. However, no new safety issues have emerged after several years of use.

Dalfampridine has a narrow therapeutic range, requiring precise dosing, as excessive amounts can increase the risk of seizures. Therefore, following dosing instructions carefully is crucial.

Since the FDA has already approved dalfampridine for use in MS, its safety in humans has been well-studied, providing reassurance about its safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for nerve injuries focus on managing symptoms rather than directly improving nerve function. 4-Aminopyridine is unique because it targets nerve conduction by blocking potassium channels, which can enhance signal transmission in damaged nerves. Unlike many traditional therapies that might require lengthy treatment durations, 4-Aminopyridine has the potential to show improvements in nerve function more rapidly. Researchers are excited about this treatment because it offers a novel approach with the possibility of improving nerve signaling and function, which could lead to better outcomes for patients with nerve injuries.

What evidence suggests that 4-aminopyridine might be an effective treatment for nerve injury?

Research has shown that 4-aminopyridine (4-AP), which participants in this trial may receive as part of the investigational treatment, may aid in nerve injuries. In earlier studies, 5 out of 6 individuals with spinal cord injuries experienced improved sensation and reduced pain, suggesting potential movement enhancement. Additionally, 4-AP has been used in individuals with multiple sclerosis (MS), where it increased walking speed by about 25%. These findings suggest that 4-AP could accelerate recovery from nerve injuries by enhancing nerve signal transmission. However, results have been mixed, necessitating further research to confirm these benefits. ^{6 7 8 9 10}

Who Is on the Research Team?

Benjamin Lee, MD

Principal Investigator

University of Arizona

John Elfar, MD

Principal Investigator

University of Arizona

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6241229/

Effectiveness of 4-Aminopyridine for the Management ... Several trials have independently found 4-AP to have promising but mixed results in reducing spasticity post SCI. ... Additional studies have also reported ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03701581

NCT03701581 | 4-aminopyridine Treatment for Nerve 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 ...

3. nature.com nature.com/articles/3101653

Effect of 4-aminopyridine on gait in ambulatory spinal cord ... Five out of six participants, with incomplete injuries, experienced improved sensation, less pain and a trend toward improved motor function.

4. sciencedirect.com sciencedirect.com/science/article/pii/S187874792301704X

Enhancing Neural Transmission in Multiple Sclerosis (4- ... For the last 30 years, small safety and efficacy trials of 4-AP were completed in MS patients. Initial studies showed improvement in visual performance, motor ...

5. ampyra-hcp.com ampyra-hcp.com/clinical-trials/

Clinical Study Results Regardless of DMT use,* AMPYRA® (dalfampridine) responders increased walking speed by an average of about 25% *AMPYRA was effective in improving walking when ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4687626/

Safety profile of dalfampridine extended release in multiple ... Conclusion. The 5-year US postmarketing safety data of dalfampridine-ER is consistent with the safety profile observed in clinical trials.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291812001579

The Safety Profile of Dalfampridine Extended Release in ... In patients with MS, dalfampridine has a narrow therapeutic range but an acceptable safety profile when used at the therapeutic dose of 10 mg twice daily.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3388528/

Extended-release dalfampridine in the management of ... No new tolerability issues or safety profile data were identified in this study. The most common treatment-emergent adverse events on extended-release ...

9. ampyra-hcp.com ampyra-hcp.com/safety-results/

Safety and Tolerability Profile The most common adverse reactions (incidence ≥ 2% and at a rate greater than placebo) for AMPYRA in MS patients were urinary tract infection, insomnia, ...

10. multiplesclerosisnewstoday.com multiplesclerosisnewstoday.com/news-posts/dalfampridine-real-world-safety-profile-trials/

Dalfampridine real-world safety profile mostly consistent ... Common side effects included urinary tract infection (UTI), dizziness and MS worsening, consistent with the therapy's known profile.