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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called resiniferatoxin (RTX) for individuals with Morton's neuroma, a condition causing painful nerve irritation in the feet. The primary aim is to determine if RTX can provide better and longer-lasting pain relief compared to current treatments, which often prove ineffective for everyone. Participants should have Morton’s neuroma with persistent pain not relieved by other treatments like painkillers or injections. Eligible participants will receive an RTX injection in their foot and be monitored to assess its effects on their pain. As a Phase 1 trial, this research focuses on understanding how RTX works in people, offering participants the opportunity to be among the first to receive this new treatment.

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 there any evidence suggesting that resiniferatoxin is likely to be safe for humans?

Research has shown that resiniferatoxin (RTX) may help reduce pain, but its safety in humans remains under investigation. Some studies have raised concerns about its potential to harm nerve cells. However, RTX is being tested for various conditions and shows promise in pain management.

Since this trial is in an early stage, the main goal is to assess RTX's safety for humans. This means some safety aspects may still be unknown. Researchers will closely monitor participants for any side effects to ensure their safety.

For more questions about the trial or RTX, consulting a healthcare professional is advisable. They can provide more details and help determine if joining the trial is suitable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Resiniferatoxin is unique because it targets the pain of Morton's neuroma in a new way. Unlike standard treatments like corticosteroid injections or surgery, which focus on reducing inflammation or removing the neuroma, resiniferatoxin works by targeting and desensitizing the nerve endings that transmit pain signals. This compound is derived from a naturally occurring plant toxin and offers the potential for long-lasting pain relief without the need for invasive procedures. Researchers are excited about resiniferatoxin because it could provide a more effective and less invasive option for patients who struggle with persistent neuroma pain.

What evidence suggests that resiniferatoxin might be an effective treatment for Morton's neuroma?

Research shows that resiniferatoxin (RTX), administered to participants in this trial, may relieve pain from Morton's neuroma, a condition often causing burning or shooting pain in the feet. Studies have found that RTX targets nerve cells to reduce pain. It may lessen both unexpected and triggered pain, easing daily activities. RTX has been researched for various long-term pain conditions, indicating its potential to manage pain effectively. Early results suggest that RTX might offer longer-lasting pain relief compared to current treatments. ^{1 3 5 6 7}

Who Is on the Research Team?

Andrew J Mannes, M.D.

Principal Investigator

National Institutes of Health Clinical Center (CC)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05695339

Resiniferatoxin for the Management of Refractory Morton s ... This is an interventional protocol to determine the safety and tolerability of resiniferatoxin (RTX) for treatment of pain from Morton's neuroma.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1526590024001512

Targeting Peripheral and Central Sensitization of Morton's ... The prevalent symptom of burning pain in MN patients reinforces the idea that RTX may provide effective pain relief in Morton's neuroma patients.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4711370/

Resiniferatoxin for Pain Treatment: An Interventional ... This review examines existing preclinical and clinical studies related to resiniferatoxin (RTX) and its potential uses in pain treatment.

4. clinicaltrials.eu clinicaltrials.eu/inn/resiniferatoxin/

Resiniferatoxin – Application in Therapy and Current ... Resiniferatoxin (RTX) is an experimental drug being studied in various clinical trials for its potential to manage severe and chronic pain conditions.

5. clinicaltrial.be clinicaltrial.be/fr/details/189477?per_page=100&recruiting=1&enrolling_by_invitation=0&active_not_recruiting=0&not_yet_recruiting=0&completed=0&only_recruiting=1&only_eligible=0

Resiniferatoxin for the Management of Refractory Morton s... It is hypothesized that RTX will provide a long-lasting reduction of the intensity of spontaneous and evoked pain and improve daily function ...

6. withpower.com withpower.com/trial/phase-1-neuroma-1-2023-c636d

Resiniferatoxin for Morton's Neuroma Pain 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 ...

7. go.drugbank.com go.drugbank.com/conditions/DBCOND0085277

Intermetatarsal Neuroma (DBCOND0085277) Associated Data ; NCT03511677. Insole on Morton's Neuroma, No drug interventions ; NCT02678793. A Study to Evaluate the Safety and Efficacy of CNTX-4975 in ...