Resiniferatoxin for Morton's Neuroma Pain

Recruiting in Palo Alto (17 mi)

Overseen by Andrew J Mannes, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: National Institutes of Health Clinical Center (CC)

Disqualifiers: Pregnancy, Diabetes, Rheumatoid arthritis, others

No Placebo Group

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}

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

Trial 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 (Neurotoxin)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Institutes of Health Clinical Center (CC) Lead Sponsor

References

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

Cutaneous Injection of Resiniferatoxin Completely Alleviates and Prevents Nerve-Injury-Induced Neuropathic Pain. [2023] Fifth lumbar (L5) nerve injury in rodent produces neuropathic manifestations in the corresponding hind paw. The aim of this study was to investigate the effect of cutaneous injection of resiniferatoxin (RTX), a TRPV1 receptor agonist, in the rat's hind paw on the neuropathic pain induced by L5 nerve injury. The results showed that intraplantar injection of RTX (0.002%, 100 µL) (1) completely reversed the development of chronic thermal and mechanical hypersensitivity; (2) completely prevented the development of nerve-injury-induced thermal and mechanical hypersensitivity when applied one week earlier; (3) caused downregulation of nociceptive pain markers, including TRPV1, IB4 and CGRP, and upregulation of VIP in the ipsilateral dorsal horn of spinal cord and dorsal root ganglion (DRG) immunohistochemically and a significant reduction in the expression of TRPV1 mRNA and protein in the ipsilateral DRG using Western blot and qRT-PCR techniques; (4) caused downregulation of PGP 9.5- and CGRP-immunoreactivity in the injected skin; (5) produced significant suppression of c-fos expression, as a neuronal activity marker, in the spinal neurons in response to a second intraplantar RTX injection two weeks later. This work identifies the ability of cutaneous injection of RTX to completely alleviate and prevent the development of different types of neuropathic pain in animals and humans.

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

Antiallodynic effect of intrathecal resiniferatoxin on neuropathic pain model of chronic constriction injury. [2018] Injuries and/or dysfunctions in the somatosensory system can lead to neuropathic pain. Transient receptor potential vanilloid sub‑type 1 (TRPV1) play an important role in the development of allodynia and hyperalgesia following injury and the ensuing inflammatory conditions. Resiniferatoxin (RTX) is an ultrapotent synthetic TRPV1 agonist and many different administration routes are available for different mechanisms and different effects. RTX is used intraperitonially as a model of neuropathic pain or epidurally and topically to produce prolonged analgesic effects. However, the use of RTX is controversial because its neurotoxicity and margin of safety have not been addressed adequately. The present study evaluates the effect of intrathecal RTX on the induction and allodynia behavior of animals submitted to neuropathic pain by chronic constriction injury (CCI).

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

Selective ablation of nociceptive neurons for elimination of hyperalgesia and neurogenic inflammation. [2022] Neuropathic pain is mediated by nociceptive neurons that selectively express the vanilloid receptor 1 (VR1). Resiniferatoxin (RTX) is an excitotoxic VR1 agonist that causes destruction of VR1-positive neurons. To determine whether RTX can be used to ablate VR1-positive neurons selectively and to eliminate hyperalgesia and neurogenic inflammation without affecting tactile sensation and motor function, the authors infused it unilaterally into the trigeminal ganglia in Rhesus monkeys.

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

P2X3-mediated peripheral sensitization of neuropathic pain in resiniferatoxin-induced neuropathy. [2022] Patients suffering from sensory neuropathy due to skin denervation frequently have paradoxical manifestations of reduced nociception and neuropathic pain. However, there is a lack of satisfactory animal models to investigate these phenomena and underlying mechanisms. We developed a mouse system of neuropathy induced by resiniferatoxin (RTX), a capsaicin analog, and examined the functional significance of P2X3 receptor in neuropathic pain. From day 7 of RTX neuropathy, mice displayed mechanical allodynia (p

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

Perineural resiniferatoxin prevents hyperalgesia in a rat model of postoperative pain. [2021] Resiniferatoxin (RTX) is a vanilloid agonist with a unique spectrum of activities. Vanilloids bind to the transient receptor potential ion channel subtype 1, a nonselective cation ionophore important in the integration of different noxious signals. Vanilloid agonists selectively decrease sensitivity to noxious stimuli. In this study, we sought to determine whether perineural RTX prevents hyperalgesia in a model of incisional pain. In a rat model, RTX was administered percutaneously to the sciatic and saphenous nerves before the plantar incision. The withdrawal response to von Frey filaments, the struggle response to pressure on the paw, and pain scoring based on weight bearing were measured before RTX and at various intervals for 8 days after RTX. A percutaneous injection of RTX (0.0003%) to the sciatic (0.1 mL) and saphenous (0.05 mL) nerves completely prevented incisional hyperalgesia. Two hours after incision, the withdrawal threshold was 51 mN without and 456 mN with RTX (P

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

Activated Glia Increased the Level of Proinflammatory Cytokines in a Resiniferatoxin-Induced Neuropathic Pain Rat Model. [2022] Administration of resiniferatoxin (RTX) can mimic the clinical symptoms of postherpetic neuralgia. However, it is unclear whether activated glia contribute to the pathogenesis of RTX-induced neuropathic pain; furthermore, the relationship between p38, N-methyl-D-aspartate receptor type 2B (NR2B) as well as proinflammatory cytokines and activated glia remains unknown.

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

Treatment of Morton neuroma with botulinum toxin A: a pilot study. [2022] Morton neuroma is a common cause of metatarsalgia of neuropathic origin. Systematic reviews suggest that insufficient studies have been performed on the efficacy of the different treatments available. OnabotulinumtoxinA has shown a degree of usefulness in other conditions associated with neuropathic pain. The aim of this study was to investigate the therapeutic potential of onabotulinumtoxinA in Morton neuroma.

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

Resiniferatoxin mediated ablation of TRPV1+ neurons removes TRPA1 as well. [2019] Resiniferatoxin, the most potent agonist of inflammatory pain/vanilloid receptor/cation channel (TRPV1) can be used for neuron subtype specific ablation of pain generating cells at the level of the peripheral nervous system by Ca(2+)-excytotoxicity. Molecular neurosurgery is an emerging technology either to alleviate severe pain in cancer or treat/prevent different local neuropathies. Our aim was determining sensory modalities that may be lost after resiniferatoxin treatment.