Morton's NeuromaPhase 1NCT05695339
Resiniferatoxin for the Management of Refractory Morton s Neuroma Pain
A Phase 1 study testing Resiniferatoxin in people with Morton's Neuroma, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Morton's Neuroma
- What is being tested?
- Resiniferatoxin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2025to 15 Oct 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Both male and female participants are eligible for study evaluation. There are no exclusions for any racial/ethnic groups. Efforts will be made to extend accrual to a representative population. In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- 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.
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- 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
- Double-barrier method (condoms, sponge, or diaphragm with spermicidal jellies or cream).
- Defined as having had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; or having a congenital or acquired condition that prevents childbearing
- Defined as at least 12 months with no menses without an alternative medical cause) [can be confirmed with follicle stimulating hormone level (FSH) in the post-menopausal range (FSH levels >=40 milli international units/mL (mIU/mL) at Screening) if the subject is not on hormonal replacement therapy]
- For males of reproductive potential who are sexually active: use of condoms or other methods to ensure effective contraception with partner for one (1) month after administration of (RTX).
- If a male of reproductive potential, unless he has a same sex partner or a partner who is sterile or at least one year post-menopausal, must agree to do the following for at least one month after receiving IP
- practice abstinence from heterosexual activity or
- use (or have their partner use) acceptable contraception (see criterion above) during heterosexual activity
- Male study participants should not donate sperm for 3 months after RTX injection.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase I Open Label Clinical Trial Using Resiniferatoxin, A Non-Opioid Medication, For the Management of Refractory Morton's Neuroma Pain
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:
Read more
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.
Read the detailed description
Study Description:
This is an interventional protocol to determine the safety and tolerability of resiniferatoxin (RTX) for treatment of pain from Morton's neuroma with a single ultrasound-guided perineural injection of (RTX). It is hypothesized that RTX will provide a long-lasting reduction of the intensity of spontaneous and evoked pain and improve daily function without interfering with other sensory modalities or motor function. The safety and efficacy of the interventional procedure will be assessed during the trial. The 3+3 design of RTX treatment will be used to assess safety and determine the Dose Limiting Toxicity (DLT). Pre- and post-procedure pain intensity assessments, including graded interference of pain with daily function and graded descriptors of neuropathic pain, will be performed to assess efficacy. This protocol is intended to test RTX as a new method for long-term relief of refractory Morton s neuroma pain. Potentially this new treatment will reduce the need for radical procedures to treat unrelenting Morton s neuroma pain.
Objectives:
Primary Objective:
-To determine the safety and tolerability of resiniferatoxin (RTX) for treatment of pain from Morton's neuroma.
Secondary Objective:
-To determine the efficacy of RTX intervention on pain intensity, interference of pain with daily function and incidence and intensity of neuropathic qualities of pain.
Endpoints:
Primary Endpoint:
-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.
Secondary Endpoints:
- Change in average worst pain (NRS) between day 21 and day 28 compared to baseline average worst pain.
- Change in pain interference on day 28 compared to screening (preinjection) using PROMIS pain tools.
Change in neuropathic pain score on day 28 compared to screening (preinjection)using painDETECT.
- Conditions
- Morton's Neuroma
- Being tested
- Resiniferatoxin
- Keywords
- Neuropathic, Forefoot, Ultra-Sound Guided, Common Plantar Digital Nerve, Perineural Injection, Trpv1, Morton's Disease
- Medical subject headings
- Morton Neuroma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ResiniferatoxinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Resiniferatoxin | Experimental | Resiniferatoxin Receives: Drug: Resiniferatoxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: day 0 (injection day) and day 28 post-injection (end-of-study).
Secondary outcomes (3)
Change in average worst pain (NRS)
Change in average worst pain (NRS) between day 21 and 28 compared to baseline average worst pain (NRS)
Measured: between day 21 and 28
Change in pain interference
Change in pain interference on day 28 compared to screening (pre-injection) using BPI-SF
Measured: Day 28
Change in neuropathic pain score
Change in neuropathic pain score on day 28 compared to screening (pre-injection) using painDETECT
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2023
- Study start13 Mar 2025
- Primary completion12 Oct 2025
- Study completion15 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Morton's NeuromaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Andrew J Mannes, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05695339
- Sponsor's protocol ID
- 10000767
- Other IDs
- 000767-CC
- Status last verified
- 9 Apr 2026
- First submitted
- 21 Jan 2023
- Last updated
- 13 Apr 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Open Label Clinical Trial Using Resiniferatoxin, A Non-Opioid Medication, For the Management of Refractory Morton's Neuroma Pain
- ClinicalTrials.gov ID
- NCT05695339
- Acronym / sponsor ID
- 10000767
- Conditions
- Morton's Neuroma
- Keywords
- Neuropathic, Forefoot, Ultra-Sound Guided, Common Plantar Digital Nerve, Perineural Injection, Trpv1, Morton's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- 13 Mar 2025 (actual)
- Primary completion
- 12 Oct 2025 (actual)
- Study completion
- 15 Oct 2025 (actual)
- First posted
- 25 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Description:
This is an interventional protocol to determine the safety and tolerability of resiniferatoxin (RTX) for treatment of pain from Morton's neuroma with a single ultrasound-guided perineural injection of (RTX). It is hypothesized that RTX will provide a long-lasting reduction of the intensity of spontaneous and evoked pain and improve daily function without interfering with other sensory modalities or motor function. The safety and efficacy of the interventional procedure will be assessed during the trial. The 3+3 design of RTX treatment will be used to assess safety and determine the Dose Limiting Toxicity (DLT). Pre- and post-procedure pain intensity assessments, including graded interference of pain with daily function and graded descriptors of neuropathic pain, will be performed to assess efficacy. This protocol is intended to test RTX as a new method for long-term relief of refractory Morton s neuroma pain. Potentially this new treatment will reduce the need for radical procedures to treat unrelenting Morton s neuroma pain.
Objectives:
Primary Objective:
-To determine the safety and tolerability of resiniferatoxin (RTX) for treatment of pain from Morton's neuroma.
Secondary Objective:
-To determine the efficacy of RTX intervention on pain intensity, interference of pain with daily function and incidence and intensity of neuropathic qualities of pain.
Endpoints:
Primary Endpoint:
-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.
Secondary Endpoints:
- Change in average worst pain (NRS) between day 21 and day 28 compared to baseline average worst pain.
- Change in pain interference on day 28 compared to screening (preinjection) using PROMIS pain tools.
Change in neuropathic pain score on day 28 compared to screening (preinjection)using painDETECT.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Resiniferatoxin | Experimental | Drug: ResiniferatoxinResiniferatoxin |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Both male and female participants are eligible for study evaluation. There are no exclusions for any racial/ethnic groups. Efforts will be made to extend accrual to a representative population. In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ResiniferatoxinAn 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. | Drug | Resiniferatoxin |
Primary outcome
The number of related Adverse Events
Time frame: day 0 (injection day) and day 28 post-injection (end-of-study)
-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
DLT or the highest dose
Time frame: day 0 (injection day) and day 28 post-injection (end-of-study).
-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
3 secondary outcomes
Change in average worst pain (NRS)
Time frame: between day 21 and 28
Change in pain interference
Time frame: Day 28
Change in neuropathic pain score
Time frame: Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Related trials for Morton's Neuroma
Not yet recruitingPhase 2
NAC-REPAIR for Post-surgical Pain
Carpal Tunnel Surgery, Trigger Finger Disorder
Recruiting
Comparative Effectiveness of Cryoablation Versus Steroid and Lidocaine Alone for Treatment of Morton's Neuroma
Morton Neuroma
Enrolling by invitation
US and MRI of the Forefoot: Intermetatarsal Bursitis or Morton's Neuroma
Intermetatarsal Bursitis, Morton Neuroma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew J Mannes, M.D. principal investigator
National Institutes of Health Clinical Center (CC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Resiniferatoxin in people with Morton's Neuroma, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of related Adverse Events (time frame: day 0 (injection day) and day 28 post-injection (end-of-study)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.