Resiniferatoxin for the Management of Refractory Morton s Neuroma Pain

NCT05695339 | Completed Phase 1 FDA Drug

• 2 other identifiers: 10000767000767-CC
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Morton's Neuroma

Keywords

Neuropathic; Forefoot; Ultra-Sound Guided; Common Plantar Digital Nerve; Perineural Injection; Trpv1; Morton's Disease

Outcome Measures

Primary Outcomes (2)

• The number of related Adverse Events

  -The number of related Adverse Events (Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials) experienced between day 0 (injection day) and day 28 post-injection

  day 0 (injection day) and day 28 post-injection (end-of-study)

• DLT or the highest dose

  -The number of related Adverse Events (Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials) experienced between day 0 (injection day) and day 28 post-injection

  day 0 (injection day) and day 28 post-injection (end-of-study).

Secondary Outcomes (3)

• Change in average worst pain (NRS)

  between day 21 and 28

• Change in pain interference

  Day 28

• Change in neuropathic pain score

  Day 28

Study Arms (1)

Resiniferatoxin

EXPERIMENTAL

Resiniferatoxin

Drug: Resiniferatoxin

Interventions

Resiniferatoxin DRUG

An injection of 1-2 ml bupivacaine 0.5% will be placed around the affected branch of the neuroma (aiming at its proximal end) and dorsal adjacent tissue including the skin dorsally to the neuroma. This is to prevent pain caused by any microscopic spills of RTX during the. A second local anesthetic depot will be placed 1-2 cm proximally to the injection site around the affected branch of the plantar nerve to prevent pain caused by passive current transmission by axonal RTX excitation. Following the course of the affected nerve branch and ultra-sound visualization of the injection site, 0.5-2 ml bupivacaine 0.5% will be injected perineurally. Once the site has sufficient nerve block, the required RTX dose in a solution of 0.25 ml will be injected directly proximal to the Morton s neuroma under ultra-sound visualization.

Resiniferatoxin

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form.
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Must be able to read, write, understand, and complete English-language study-related forms and adequately communicate in English.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged 18 and older.
• In good general health as evidenced by medical history.
• Diagnosed with one painful Morton s neuroma in the index foot
• Has not attained satisfactory pain relief with conservative, oral analgesic and at least one kind of injection treatment for Morton s neuroma.
• Exhibits moderate to severe foot pain due to the Morton s neuroma (average worst pain \>= 5 on the 0-10 numeric pain rating scale NRS) as assessed verbally at \>= 3 individual days during prescreening.
• For females of reproductive potential who are sexually active: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional one (1) month after administration of RTX.
• If a female, be sterile (surgically or biologically) \* or at least one year postmenopausal\*\*, or have a monogamous partner who is surgically sterile, or have a same sex partner, or if in a heterosexual relationship, must agree to do the following for at least one month after receiving investigational product (IP):
• Practice abstinence, or
• Use at least one of the following medically acceptable methods of birth control:
• Hormonal methods such as oral, implantable, injectable, vaginal ring, or transdermal contraceptives (must have started a minimum of 1 full cycle, based on the subject s usual menstrual cycle period, before IP dose
• Intrauterine device

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnancy or lactation.
• Has a known allergy or hypersensitivity to chili peppers or capsaicin.
• Has a known allergy to local anesthetics.
• Has active or history of rheumatoid arthritis or peripheral neuropathy.
• Has a prolonged baseline QTc interval exceeding 480 milliseconds.
• Current presentation of other currently painful pathology of the same foot affected by Morton s neuroma, including, but not limited to, hallux valgus, plantar fasciitis, hammer toes, metatarsalgia, bursitis.
• History of injection and/or ablation treatments treatment in the affected foot up to one month previous to study participation.
• History of nerve excision due to Morton s neuroma in the location to be treated with RTX.
• Active cutaneous disease, inflammation or infection at the anticipated site of study drug injection.
• Has diabetes mellitus or peripheral vascular disease whether poorly managed or stable.
• Has more than one Morton s neuroma in the index foot scheduled to receive the treatment intervention.
• Other clinically significant condition that might interfere with study participation or greatly increases safety risk to the subject, as judged by the study investigator.
• Concurrent treatment with another investigational drug or other intervention within last month.
• Cognitive or language difficulties that would impair comprehension or completion of the assessment instruments.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Morton Neuroma

Interventions

resiniferatoxin

Condition Hierarchy (Ancestors)

Metatarsalgia; Foot Diseases; Musculoskeletal Diseases; Joint Diseases; Neuralgia; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Andrew J Mannes, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2023
• First Posted: January 25, 2023
• Study Start: March 13, 2025
• Primary Completion: October 12, 2025
• Study Completion: October 15, 2025
• Last Updated: April 13, 2026

Record last verified: 2026-04-09

Locations

US (1)