Tetrodotoxin for Chemotherapy-Induced Neuropathic Pain

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

35 Participants Needed

Trial Summary

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.

What data supports the idea that Tetrodotoxin for Chemotherapy-Induced Neuropathic Pain (also known as: Single Cycle Tetrodotoxin, Halneuron) is an effective drug?

The available research shows that Tetrodotoxin (TTX) can be effective for treating chemotherapy-induced neuropathic pain. In a study with patients experiencing this type of pain, those who received TTX reported significant pain relief compared to those who received a placebo, especially at higher doses. Another analysis found that TTX increased the number of patients who experienced at least a 30% improvement in pain intensity. While TTX did lead to some mild side effects, it did not increase the risk of serious side effects. Overall, these studies suggest that TTX can provide meaningful pain relief for patients with chemotherapy-induced neuropathic pain. ^{1 2 3 4 5}

What safety data exists for Tetrodotoxin in treating chemotherapy-induced neuropathic pain?

Tetrodotoxin (TTX) has been evaluated in several studies for its safety in treating cancer-related pain, including chemotherapy-induced neuropathic pain. A systematic review and meta-analysis found that TTX significantly increased the number of responders to pain treatment and the number of patients experiencing non-severe adverse events, but did not increase the risk of serious adverse events. In a randomized, double-blind trial, most adverse events were mild or moderate, with oral paresthesia and hypoesthesia being the most common. An open-label study reported mild sensory phenomena and nausea, with two serious adverse events of truncal and gait ataxia that resolved over time. Another randomized study also noted mild sensory phenomena and nausea, with one serious adverse event of truncal and gait ataxia. Overall, TTX was found to be generally safe, with most adverse events being mild or moderate. ^{1 2 3 4 5}

Is the drug Tetrodotoxin (Halneuron) a promising treatment for chemotherapy-induced neuropathic pain?

Yes, Tetrodotoxin (Halneuron) shows promise as a treatment for chemotherapy-induced neuropathic pain. Studies indicate it can effectively reduce pain and improve quality of life for patients, with significant pain relief observed in clinical trials. ^{1 2 3 4 6}

What is the purpose of this trial?

To be eligible for the trial, subjects must have ongoing moderate to severe neuropathic pain related to a prior course of platinum and/or taxane chemotherapy and have no clinical evidence of actively progressive disease. The trial period will comprise a Screening period (up to 35 Days), randomization and a 4-day treatment period, followed by a 12-week follow up period (12 weeks total after initial treatment), and an End-of-Trial/Follow-up visit which will occur at Week 13. This is a study to research the effects of the study drug on neuropathic pain compared placebo.

Research Team

Walter Korz

Principal Investigator

COO

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

References

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

Tetrodotoxin inhibits the development and expression of neuropathic pain induced by paclitaxel in mice. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Tetrodotoxin for Chemotherapy-Induced Neuropathic Pain: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Dose Finding Trial. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Security of Tetrodotoxin in the Treatment of Cancer-Related Pain: Systematic Review and Meta-Analysis. [2023]

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

An open-label, multi-dose efficacy and safety study of intramuscular tetrodotoxin in patients with severe cancer-related pain. [2007]

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

Tetrodotoxin for moderate to severe cancer pain: a randomized, double blind, parallel design multicenter study. [2008]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Tetrodotoxin, a Potential Drug for Neuropathic and Cancer Pain Relief? [2021]