Resiniferatoxin for Morton's Neuroma Pain

Overseen By Andrew J Mannes, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institutes of Health Clinical Center (CC)

Disqualifiers: Pregnancy, Diabetes, Rheumatoid arthritis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 1 day

24 Participants Needed

Trial Summary

What is the purpose of this trial?

Morton s neuroma is an irritation of the nerves that affect the feet. People with this condition may have burning or shooting pain in the balls of their feet. They may also have numbness in adjacent areas. These symptoms may become more frequent and severe over time. The pain may become permanent. Current treatments tend to be short-lived, and they do not work in all people. Better treatments are needed. Objective: To test a study drug, resiniferatoxin (RTX), in people with Morton s neuroma. Eligibility: Healthy people aged 18 and older who have Morton s neuroma and have tried other standard treatments that did not ease their pain. Design: Participants will be involved in the study up to 4 months. They will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. They will have X-rays of their affected feet. They will have tests to assess their pain and how their feet react to touch and changes in temperature. They will complete questionnaires about their pain. RTX is injected into the foot at the site of the nerve pain. Participants will receive a shot to numb the area before the RTX is administered. They will be monitored in the clinic for 4 hours after they receive the RTX. Participants will receive up to 5 follow-up phone calls per week. Each call will take 5 to 10 minutes. They will be asked about their foot pain and whether they have had any side effects from the RTX. Participants will return to the clinic 4 weeks after the treatment. Previous tests will be repeated.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are currently receiving another investigational drug or treatment, you must stop it at least one month before participating in this study.

Is resiniferatoxin (RTX) generally safe for use in humans?

Research on resiniferatoxin (RTX) shows it can be effective in reducing pain, but its safety is not fully established, as concerns about its neurotoxicity and safety margin have been raised. Studies in animals have shown it can alleviate pain without affecting movement, but more human safety data is needed. ^{1 2 3 4 5}

How does the drug resiniferatoxin (RTX) differ from other treatments for Morton's neuroma pain?

Resiniferatoxin (RTX) is unique because it targets and ablates specific pain-generating neurons by activating the TRPV1 receptor, which can lead to long-lasting pain relief. This mechanism is different from other treatments like botulinum toxin, which may not specifically target these pain pathways. ^{1 2 6 7 8}

Research Team

Andrew J Mannes, M.D.

Principal Investigator

National Institutes of Health Clinical Center (CC)

Eligibility Criteria

This trial is for adults over 18 in good health with Morton's neuroma, who've tried other pain treatments without relief. They must be willing to follow the study procedures and use effective contraception if of reproductive potential. Excluded are those with allergies to local anesthetics or chili peppers, certain medical conditions, or concurrent investigational drug use.

Inclusion Criteria

Ability to read, write, understand, and complete English-language study-related forms and communicate in English

I will use effective birth control methods for a month after getting RTX treatment.

I am eligible regardless of my gender or race.

Exclusion Criteria

Cognitive or language difficulties that would impair comprehension or completion of the assessment instruments

I have another painful foot condition besides Morton's neuroma.

Concurrent treatment with another investigational drug or other intervention within last month

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

RTX is injected into the foot at the site of the nerve pain. Participants receive a shot to numb the area before RTX is administered and are monitored for 4 hours post-injection.

1 day

1 visit (in-person)

Follow-up

Participants receive up to 5 follow-up phone calls per week to assess foot pain and side effects. They return to the clinic 4 weeks after treatment for repeated tests.

4 weeks

5 phone calls per week, 1 visit (in-person)

Long-term Follow-up

Participants are monitored for safety and effectiveness after the initial follow-up period.

4 weeks

Treatment Details

Interventions

• Resiniferatoxin

Trial Overview The trial tests resiniferatoxin (RTX), a new drug injected into the foot to manage severe pain from Morton's neuroma. Participants will undergo screening, receive RTX treatment, and have follow-up calls and clinic visits to monitor their condition and any changes in their foot pain.

Participant Groups

Group I: Resiniferatoxin Experimental Treatment 1 Intervention

Resiniferatoxin

Who Is Running the Clinical Trial?

National Institutes of Health Clinical Center (CC)

Lead Sponsor

Trials

391

Recruited

30,880,000+

Findings from Research

Intraplantar injection of resiniferatoxin (RTX) completely reversed chronic thermal and mechanical hypersensitivity in rats with L5 nerve injury, demonstrating its potential as an effective treatment for neuropathic pain.

RTX not only alleviated existing pain but also prevented the onset of hypersensitivity when administered prior to nerve injury, indicating its strong therapeutic potential in managing neuropathic pain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous Injection of Resiniferatoxin Completely Alleviates and Prevents Nerve-Injury-Induced Neuropathic Pain. Javed, H., Johnson, AM., Challagandla, AK., et al.[2023]

Intrathecal administration of resiniferatoxin (RTX) showed significant antiallodynic effects in mice with neuropathic pain induced by chronic constriction injury, indicating its potential as an effective treatment for pain relief.

POST-treatment with RTX not only alleviated pain but also significantly reduced the expression of the TRPV1 receptor in dorsal root ganglia, suggesting it may help reverse central sensitization associated with neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiallodynic effect of intrathecal resiniferatoxin on neuropathic pain model of chronic constriction injury. Parisi, JR., Martins de Andrade, AL., Torres Silva, JR., et al.[2018]

Resiniferatoxin (RTX) selectively ablates nociceptive neurons expressing the vanilloid receptor 1 (VR1), effectively reducing high-intensity pain perception and neurogenic inflammation in Rhesus monkeys without affecting normal touch sensation or motor function.

The study demonstrated that RTX infusion into the trigeminal ganglia led to significant reductions in pain responses (e.g., eye blinks and squinting) while showing no neurological deficits or toxicity, suggesting its potential as a treatment for pain syndromes like trigeminal neuralgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective ablation of nociceptive neurons for elimination of hyperalgesia and neurogenic inflammation. Tender, GC., Walbridge, S., Olah, Z., et al.[2022]

The study developed a mouse model of sensory neuropathy using resiniferatoxin (RTX), which revealed that mice experienced both mechanical allodynia and thermal hypoalgesia, indicating complex pain responses despite skin denervation.

Increased expression of the P2X3 receptor in dorsal root ganglion neurons was linked to mechanical allodynia, and blocking this receptor with specific antagonists effectively reduced pain, suggesting it as a potential therapeutic target for neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

P2X3-mediated peripheral sensitization of neuropathic pain in resiniferatoxin-induced neuropathy. Hsieh, YL., Chiang, H., Lue, JH., et al.[2022]

In a rat model, perineural administration of resiniferatoxin (RTX) completely prevented hyperalgesia (increased sensitivity to pain) following an incision, demonstrating its efficacy in managing postoperative pain.

RTX effectively blocked pain responses without affecting nonpainful sensations or motor functions, indicating a potential for safe pain management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perineural resiniferatoxin prevents hyperalgesia in a rat model of postoperative pain. Kissin, I., Davison, N., Bradley, EL.[2021]

Resiniferatoxin (RTX) induces neuropathic pain in rats, characterized by mechanical allodynia and thermal hyperalgesia, with significant changes in proinflammatory cytokines and glial activation observed for at least 49 days.

Inhibiting activated glia with drugs like minocycline and fluorocitrate not only reduced pain behaviors but also decreased the expression of pain-related proteins, suggesting a potential new treatment strategy for postherpetic neuralgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activated Glia Increased the Level of Proinflammatory Cytokines in a Resiniferatoxin-Induced Neuropathic Pain Rat Model. Lei, Y., Sun, Y., Lu, C., et al.[2022]

In a pilot study involving 17 patients with Morton neuroma, onabotulinumtoxinA injections significantly reduced pain levels, with average pain scores decreasing from 7 to 3.7 over three months, and 70.6% of patients reported improvement.

The treatment also enhanced foot function, as indicated by improvements in the Foot Health Status Questionnaire, with no adverse effects reported, suggesting that onabotulinumtoxinA could be a safe and effective option for managing Morton neuroma pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Morton neuroma with botulinum toxin A: a pilot study. Climent, JM., Mondéjar-Gómez, F., Rodríguez-Ruiz, C., et al.[2022]

Resiniferatoxin effectively targets and ablates pain-generating cells in the peripheral nervous system, leading to a loss of sensitivity to heat stimuli in adult mice, while also affecting sensitivity to specific pain-related chemical stimuli.

The treatment results in a complex change in sensory perception, causing desensitization to heat and sensitization to cold, suggesting that surviving sensory neurons may compensate for lost pain signals, highlighting the intricate balance of pain and temperature sensation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resiniferatoxin mediated ablation of TRPV1+ neurons removes TRPA1 as well. Pecze, L., Pelsoczi, P., Kecskés, M., et al.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Cutaneous Injection of Resiniferatoxin Completely Alleviates and Prevents Nerve-Injury-Induced Neuropathic Pain. [2023]

2. Poland pubmed.ncbi.nlm.nih.gov

Antiallodynic effect of intrathecal resiniferatoxin on neuropathic pain model of chronic constriction injury. [2018]

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

Selective ablation of nociceptive neurons for elimination of hyperalgesia and neurogenic inflammation. [2022]

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

P2X3-mediated peripheral sensitization of neuropathic pain in resiniferatoxin-induced neuropathy. [2022]

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

Perineural resiniferatoxin prevents hyperalgesia in a rat model of postoperative pain. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Activated Glia Increased the Level of Proinflammatory Cytokines in a Resiniferatoxin-Induced Neuropathic Pain Rat Model. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Treatment of Morton neuroma with botulinum toxin A: a pilot study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Resiniferatoxin mediated ablation of TRPV1+ neurons removes TRPA1 as well. [2019]