Tetrodotoxin for Chemotherapy-Induced Neuropathic Pain

No longer recruiting at 20 trial locations

Overseen By John Duffy, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wex Pharmaceuticals Inc.

Must not be taking: Opioids, Lidocaine, Antidepressants, others

Disqualifiers: Peripheral neuropathy, Impaired renal function, Bone metastases, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 4 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how tetrodotoxin (also known as Halneuron) can relieve neuropathic pain from past chemotherapy treatments, specifically platinum and taxane types. Participants will receive either tetrodotoxin or a placebo to determine which more effectively reduces pain. It suits individuals with moderate to severe chemotherapy-related nerve pain for at least three months who are not currently experiencing progressive cancer. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to developing new pain relief options.

Do I have to stop taking my current medications?

You may need to stop or adjust some medications. If you're using therapies for neuropathic pain, opioids, or certain other medications, they must be stable for at least 60 days before joining the trial. Some medications, like lidocaine or sodium channel antiarrhythmics, must be stopped 30 days before. Check with the trial team for specifics.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that tetrodotoxin, the treatment under study for chemotherapy-induced pain, is generally well-tolerated. In earlier studies, most side effects were mild or moderate. The most common issues included tingling in the mouth, reported by about 29.6% of participants, and numbness in the mouth, reported by about 24.8%. This suggests that while some side effects may occur, they are usually not severe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neuropathic pain?

Researchers are excited about using tetrodotoxin for chemotherapy-induced neuropathic pain because it offers a novel approach compared to existing treatments. Unlike standard options such as gabapentin or duloxetine, which target broader nerve pain pathways, tetrodotoxin specifically blocks sodium channels on nerves, potentially reducing pain more precisely. Additionally, this treatment is administered via a subcutaneous injection, which could offer more direct and rapid relief. This targeted mechanism and delivery method may provide quicker, more effective pain management for patients suffering from the debilitating effects of chemotherapy-induced neuropathy.

What evidence suggests that Tetrodotoxin might be an effective treatment for chemotherapy-induced neuropathic pain?

Research has shown that tetrodotoxin (TTX) might help reduce neuropathic pain, which is pain caused by nerve damage. Studies have found that TTX can lessen pain in individuals with cancer-related and chronic pain. In tests with various types of nerve pain, TTX reduced pain behaviors. Specifically, for chemotherapy-related pain, TTX showed promise in easing discomfort from treatments like platinum and taxane chemotherapy. In this trial, participants will receive either TTX or a placebo to evaluate its effectiveness in managing chemotherapy-induced nerve pain. ^{1 2 3 4 6}

Who Is on the Research Team?

Walter Korz

Principal Investigator

COO

Are You a Good Fit for This Trial?

Adults aged 21+ with moderate to severe nerve pain due to chemotherapy (platinum/taxane) for at least 3 months, who are not currently undergoing treatment for cancer progression. Participants must be able to avoid pregnancy and complete questionnaires in English or the local language.

Inclusion Criteria

I have had stable nerve pain for at least 14 days.

I am fully active or can carry out light work.

I am 21 years old or older.

Exclusion Criteria

Any other condition that in the opinion of the investigators is likely to interfere with treatment, impede data collection, or that poses a risk to the subject

I need medication regularly to prevent vomiting.

You are not expected to live for more than 8 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

5 weeks

Treatment

Participants receive either Tetrodotoxin or placebo via SC injection twice daily for 4 days

4 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Weekly assessments

End-of-Trial/Follow-up

Final assessment of participants at the end of the trial

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Single Cycle Tetrodotoxin

Trial Overview The trial is testing Tetrodotoxin's effectiveness against neuropathic pain from chemotherapy compared to a placebo. It includes a screening period, two weeks of baseline pain assessment, a four-day treatment phase, and follows up for twelve weeks.

How Is the Trial Designed?

Group I: Tetrodotoxin for injection Active Control 1 Intervention

30 µg, 1 ml SC injection in the thigh or abdomen, twice daily for 4 Days

Group II: Placebo Placebo Group 1 Intervention

1.0 mL of placebo, SC injection in the thigh or abdomen, twice daily for 4 Days

Who Is Running the Clinical Trial?

Wex Pharmaceuticals Inc.

Lead Sponsor

Trials

6

Recruited

510+

Published Research Related to This Trial

In a study involving 125 patients with chemotherapy-induced neuropathic pain, tetrodotoxin (TTX) showed promising trends in efficacy, particularly at the 30 µg BID dose, which demonstrated significant differences in pain response compared to placebo.

Most adverse events were mild to moderate, with oral paresthesia and hypoesthesia being the most common, indicating that TTX may be a safe option for managing this type of pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrodotoxin for Chemotherapy-Induced Neuropathic Pain: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Dose Finding Trial. Goldlust, SA., Kavoosi, M., Nezzer, J., et al.[2021]

Tetrodotoxin (TTX) demonstrated significant analgesic efficacy in treating cancer-related pain, with a notable increase in the number of patients experiencing at least a 30% improvement in pain intensity based on a meta-analysis of five clinical studies.

While TTX was associated with a higher incidence of non-severe adverse events, it did not increase the risk of serious adverse events, suggesting it may be a safer option for pain management in cancer patients, though further studies with larger sample sizes are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Security of Tetrodotoxin in the Treatment of Cancer-Related Pain: Systematic Review and Meta-Analysis. Huerta, MÁ., de la Nava, J., Artacho-Cordón, A., et al.[2023]

Low doses of tetrodotoxin (TTX) effectively reduced the expression of neuropathic pain symptoms, such as mechanical allodynia and cold allodynia, in mice treated with paclitaxel, indicating its potential as a treatment for chemotherapy-induced pain.

TTX did not show any signs of toxicity or motor incoordination, suggesting that it is a safe option for preventing and treating neuropathic pain without affecting normal sensory perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrodotoxin inhibits the development and expression of neuropathic pain induced by paclitaxel in mice. Nieto, FR., Entrena, JM., Cendán, CM., et al.[2022]

In a study involving 82 patients with moderate to severe cancer pain, tetrodotoxin showed a nonstatistically significant trend towards increased pain relief compared to placebo, suggesting potential analgesic effects.

Secondary analyses indicated that tetrodotoxin may significantly reduce pain levels and opioid use while improving quality of life, although further research is needed to confirm these findings with a more robust composite endpoint.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrodotoxin for moderate to severe cancer pain: a randomized, double blind, parallel design multicenter study. Hagen, NA., du Souich, P., Lapointe, B., et al.[2008]

Tetrodotoxin (TTX) effectively blocks voltage-gated sodium channels (VGSCs) that are involved in pain signaling, showing significant analgesic effects in rodent models of neuropathic pain, which supports its clinical development for treating chemotherapy-induced and cancer-related pain.

Despite its potential therapeutic benefits, TTX can produce toxic effects at therapeutic doses, highlighting the need for careful consideration of safety when developing treatments based on this neurotoxin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrodotoxin, a Potential Drug for Neuropathic and Cancer Pain Relief? González-Cano, R., Ruiz-Cantero, MC., Santos-Caballero, M., et al.[2021]

Tetrodotoxin, a sodium channel blocker, was found to be effective in relieving severe cancer pain in a Phase IIa study involving 24 patients, with 17 out of 31 treatments resulting in significant pain reduction lasting up to two weeks.

The treatment was generally safe, with mild side effects like transient tingling and nausea, although two patients experienced serious adverse events that resolved over time, indicating a need for further research into its analgesic mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label, multi-dose efficacy and safety study of intramuscular tetrodotoxin in patients with severe cancer-related pain. Hagen, NA., Fisher, KM., Lapointe, B., et al.[2007]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33805908/

Tetrodotoxin for Chemotherapy-Induced Neuropathic Pain This randomized, double-blind, dose-finding study was undertaken to explore safety and trends in efficacy of four TTX doses and to identify a dose for further ...

2. ir.dwtx.com ir.dwtx.com/news/press-releases/detail/138/dogwood-therapeutics-announcesenrollment-of-first-fifty

Dogwood Therapeutics Announces Enrollment of First Fifty ... In clinical studies, Halneuron® treatment has demonstrated pain reduction in pain related to general cancer and in pain related to chronic ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05359133

NCT05359133 | A Randomized, Double-Blind, Placebo ... This is a study to research the effects of the study drug on neuropathic pain compared placebo.

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/580255

Efficacy and Safety Study of Halneuron in the Treatment ... Neuropathic pain has been present and is attributed to platinum and/or taxane chemotherapy. Patient has received a cancer chemotherapy regimen ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10221257/

Efficacy and Security of Tetrodotoxin in the Treatment of ... In addition, TTX reduced pain behaviors in different models of neuropathic pain, including neuropathic pain induced by nerve injury [29,32], ...

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/580255

Efficacy and Safety Study of Halneuron in the Treatment ... Efficacy and Safety Study of Halneuron in the Treatment of Chemotherapy-Induced Neuropathic Pain ... pain outcomes including sleep quality, fatigue and ...