Botox for Neuropathic Pain

Overseen By Isabel Moreno Hay, DDS PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Isabel Moreno Hay

Disqualifiers: Systemic nerve disorders, Bleeding disorders, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Botox can reduce pain for individuals with ongoing nerve pain in the jaw or teeth area, known as dentoalveolar neuropathic pain. The trial involves injecting Botox directly into the painful area to assess its effect on pain intensity over several months. Patients who have not found relief with standard pain medications and continue to experience pain might be suitable candidates for this trial. Participants will record their pain levels in a diary to help researchers evaluate the treatment's impact. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a potential new pain management option.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should have intractable pain to conventional treatments like anticonvulsants, SNRIs, or tricyclic antidepressants, which suggests you might continue them. Please confirm with the trial coordinators.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, it mentions that participants should have intractable pain despite using conventional treatments like anticonvulsants, SNRIs, or tricyclic antidepressants, which suggests you might continue your current medications.

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

Research has shown that Botox, a form of onabotulinum toxin A, is generally safe for patients. One study found no major side effects. About 41.5% of people using Botox and 43.1% in another group experienced some side effects, but they were not serious. The FDA has approved Botox for treating conditions like chronic migraines, indicating its safety for certain uses. This study examines how Botox can help with a new type of pain. While still under investigation, previous research suggests that Botox is usually safe for use. ^{1 2 3 4 5}

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

Unlike the standard treatments for neuropathic pain, which often involve medications like anticonvulsants and antidepressants, onabotulinum toxin A (Botox) offers a unique approach. This treatment works by blocking the release of neurotransmitters that signal pain, providing relief in a way that targets the root mechanism of pain transmission. Researchers are excited because Botox is administered via injection directly into the site of pain, potentially offering localized relief with fewer systemic side effects. Additionally, Botox could offer longer-lasting pain relief compared to traditional oral medications, which might need to be taken daily.

What evidence suggests that this treatment might be an effective treatment for neuropathic pain?

Research has shown that onabotulinum toxin A (BoNT-A), which participants in this trial will receive, can reduce various types of nerve pain, including pain from spinal cord injuries. Studies have found that injecting BoNT-A into painful areas significantly lowers pain levels. For instance, in one study, patients reported a substantial drop in their average pain scores. Another study found that repeated treatments led to further improvement over time. These findings suggest that BoNT-A could be a viable option for easing pain in individuals with ongoing nerve pain issues. ^{3 6 7 8 9}

Who Is on the Research Team?

Jeffrey P Okeson, DMD

Principal Investigator

Associate Professor

Are You a Good Fit for This Trial?

This trial is for individuals with ongoing dentoalveolar pain that hasn't improved with standard oral or topical medications. Participants must have signs of trigeminal nerve dysfunction and no other sources of pain, not be allergic to Botox components, have no systemic nerve/muscle disorders, bleeding issues, swallowing/breathing difficulties, and not be pregnant or breastfeeding.

Inclusion Criteria

My nerve pain does not improve with standard pain medication.

Subject consent to participate in the study.

I have ongoing dental pain with signs of nerve issues in my face, and other causes have been excluded.

Exclusion Criteria

I have breathing problems.

You are allergic to onabotulinum toxin or any of its ingredients.

I have a bleeding disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Monitoring

Eligible subjects complete a pain diary indicating their pain intensity by means of a visual analog scale during one month to establish a baseline

4 weeks

Treatment

50 U of BoNT-A is injected into the painful dentoalveolar area, and subjects monitor VAS daily for 3 months. The infiltration is repeated a second time following the same protocol

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment using a daily pain diary

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• onabotulinum toxin A

Trial Overview The study tests the effect of injecting 50 units of onabotulinum toxin A (Botox) into areas affected by neuropathic pain in the mouth. It's a small-scale experiment involving 10 patients who will record their pain levels daily before and after two injections over three months.

How Is the Trial Designed?

Group I: BOTOX Experimental Treatment 1 Intervention

Onabotulinum toxin A is distributed in 50 unit (50U) vacuum-dried powder bottles by Allergan (BOTOX (R)) for reconstitution only with sterile, preservative-free 0.9% Sodium Chloride Injection prior to injection. 1 mL of diluent will be drawn up to obtain a resulting dose of 10 U per 0.2 mL and injected into the vial. The BOTOX(R) will then be gently mixed with the saline by rotating the vial. The date and time of reconstitution will be recorded on the package on the label. BOTOX should be administered within 24 hours after reconstitution and stored in a refrigerator (2-8 °C). Each patient will receive 50 U of onabotulinum toxin A.

onabotulinum toxin A is already approved in United States, European Union for the following indications:

Approved in United States as Botox for:

• Adult spasticity
• Cervical dystonia in adults
• Severe axillary hyperhidrosis
• Blepharospasm associated with dystonia in a beneficiary 12 years of age and older
• Strabismus in a beneficiary 12 years of age and older

Approved in European Union as Botox for:

• Muscle spasms
• Detrusor muscle contraction
• Excessive sweat gland activity
• Chronic migraine prevention

Who Is Running the Clinical Trial?

Isabel Moreno Hay

Lead Sponsor

Trials

2

Recruited

50+

Allergan Sales, LLC

Industry Sponsor

Trials

10

Recruited

6,700+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

In a study involving 18 patients with painful diabetic polyneuropathy, treatment with onabotulinumtoxinA (BoNT/A) significantly decreased both tactile and mechanical pain thresholds over 12 weeks, indicating its potential efficacy in improving sensory perception.

The results suggest that BoNT/A may help alleviate symptoms of diabetic neuropathic pain, but further research is needed to understand its mechanisms and to explore its potential in preventing injuries due to reduced sensation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OnabotulinumtoxinA improves tactile and mechanical pain perception in painful diabetic polyneuropathy. Chen, WT., Yuan, RY., Chiang, SC., et al.[2022]

OnabotulinumtoxinA is generally considered safe and effective for both cosmetic and medical treatments, with minimal adverse events reported.

A case study is presented where a patient experienced neuropathic pruritus five days after receiving onabotulinumtoxinA for neuromuscular pain, emphasizing the need for awareness and management of this potential side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pruritus associated with onabotulinumtoxinA treatment of neuromuscular pain. Ho, D., Jagdeo, J.[2018]

Botulinum toxin type A has shown promise in treating chronic pain conditions with a neuropathic component, such as postherpetic neuralgia and diabetic neuropathy, based on a review of existing literature.

Fractioned injections of botulinum toxin type A may be a safe and effective method for managing these types of pain, suggesting a potential new avenue for treatment in patients suffering from neuropathic pain syndromes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous and perineural botulinum toxin type a for neuropathic pain: a descriptive review. Fabregat, G., De Andrés, J., Villanueva-Pérez, VL., et al.[2013]

Botulinum neurotoxins (BoNTs), particularly onabotulinumtoxinA, have been shown to be effective in treating neuropathic pain, with strong evidence supporting their use in conditions like postherpetic neuralgia and trigeminal neuralgia.

BoNTs are probably effective for other types of neuropathic pain, such as posttraumatic neuralgia and painful diabetic neuropathy, but more research is needed to determine the best dosages and injection techniques for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum Toxin Treatment of Neuropathic Pain. Mittal, SO., Safarpour, D., Jabbari, B.[2018]

Botulinum toxin type A (BoNT-A) significantly reduces mechanical and cold allodynia in a rat model of neuropathic pain, with effective doses ranging from 10 to 40 U.kg(-1).

However, higher doses of 30 and 40 U.kg(-1) were associated with decreased motor performance, indicating a potential side effect that needs to be considered in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of botulinum toxin A on mechanical and cold allodynia in a rat model of neuropathic pain. Park, HJ., Lee, Y., Lee, J., et al.[2013]

An 80-year-old man with severe post-herpetic neuralgia experienced significant pain relief after receiving multiple injections of botulinum toxin type A (BTX-A), which is not commonly used for neuropathic pain.

The pain relief lasted for 52 days, suggesting that BTX-A may be an effective treatment option for patients with neuropathic pain that does not respond to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin A relieved neuropathic pain in a case of post-herpetic neuralgia. Liu, HT., Tsai, SK., Kao, MC., et al.[2018]

AbobotulinumtoxinA, approved by the FDA in 2009 for facial aesthetics, is generally well tolerated and has a safety profile similar to other botulinum neurotoxin type A products.

The article discusses various clinical applications and indications for abobotulinumtoxinA, along with important information on handling, storage, and dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of AbobotulinumtoxinA (Dysport). Lorenc, ZP., Kenkel, JM., Fagien, S., et al.[2016]

Botulinum Toxin type A (BTX-A) shows potential in treating neuropathic pain in individuals with spinal cord injuries, but the current evidence is limited to only 2 case reports and 2 randomized control trials.

While initial results suggest that subcutaneous injections of BTX-A may provide some benefit, more rigorous and comprehensive studies are needed to determine effective dosing, application schedules, and long-term safety for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical review of the use of Botulinum Toxin type A in managing central neuropathic pain in patients with spinal cord injury. Lakra, C., Cohen, H.[2022]

In a randomized, double-blind, placebo-controlled trial involving 152 patients with peripheral neuropathic pain, botulinum toxin A significantly reduced pain intensity over 24 weeks compared to placebo, demonstrating its efficacy as a treatment option.

The only reported adverse effect was pain at the injection site, which occurred similarly in both the botulinum toxin A and placebo groups, indicating that the treatment is generally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial. Attal, N., de Andrade, DC., Adam, F., et al.[2022]

Botulinum neurotoxin, particularly onabotulinum toxin type A, shows promise in treating neuropathic pain, with most studies reporting positive outcomes despite variations in methods.

There is a need for larger and more rigorously designed clinical trials to definitively establish the efficacy of botulinum neurotoxin for neuropathic pain, as current studies vary widely in formulation, dosage, and injection techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum Neurotoxin for the Treatment of Neuropathic Pain. Egeo, G., Fofi, L., Barbanti, P.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10637322/

Effectiveness of Botulinum Toxin in the Treatment of ... The utilization of BTX-A in the treatment of various forms of neuralgia and neuropathic pain shows promising outcomes in terms of reducing pain ...

2. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00716/full

Botulinum Neurotoxin for the Treatment of Neuropathic Pain BoNT/A (200 U) subcutaneous administration into the painful area proved effective in a trial on 40 patients affected by SCI-associated neuropathic pain, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12423104/

Real‐World Evaluation of Botulinum Toxin A in Focal ... Mean self‐reported improvement increased from 30.7% at Cycle 2 to 51.0% at Cycle 5 (p < 0.001). PGIC and pain intensity also showed significant ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0041010123001940

Botulinum toxin A and neuropathic pain: An update Botulinum toxin type A has therapeutic value in refractory neuropathic pain or idiopathic trigeminal neuralgia, due to its sustained therapeutic ...

5. thejournalofheadacheandpain.biomedcentral.com thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-024-01926-9

Efficacy and safety profile of Onabotulinum toxin-A injection at ... Results. The average pain scores and frequency of pain decreased significantly (p-value < 0.001). The mean baseline pain score before the ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/103000s5236lbl.pdf

BOTOX (onabotulinumtoxinA) Label - accessdata.fda.gov Safety and effectiveness of BOTOX have not been established for the treatment of upper limb spasticity in pediatric patients, and for the treatment of lower ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6190814/

Botulinum toxin-A for the treatment of neuralgia Regarding the safety of BTX-A, no significant adverse effects were noted. Overall, 59 out of 142 (41.5%) patients in the BTX-A group and 59 out of 137 (43.1%) ...

8. rxabbvie.com rxabbvie.com/pdf/botox_pi.pdf

Botox Therapeutic Safety and effectiveness of BOTOX have not been established for the treatment of axillary hyperhidrosis in pediatric patients under age 18. Blepharospasm and ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557387/

Botulinum Toxin - StatPearls - NCBI Bookshelf Older Patients: The safety profiles of geriatric patients and those younger than 65 years old were found to be similar in placebo-controlled ...