Intraoral Administration of Botox in Patients With Dentoalveolar Neuropathic Pain

Neuropathic Pain Clinical Trial

Official title:

Intraoral Administration of Onabotulinum Toxin A for Continuous Neuropathic Pain: a Single Subject Experimental Design

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03848143
• Other study ID #: 45231
• Secondary ID: IIT-10247
• Status: Recruiting
• Phase: Phase 2
• Start date: September 11, 2019
• Est. completion date: December 31, 2025

Study information

• Verified date: December 2023
• Source: University of Kentucky
• Contact: Isabel Moreno Hay, DDS PhD
• Phone: 8593233440
• Email: imo226[@]uky.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Onabotulinum toxin type A (BoNT-A) is a potent neurotoxin that has been reported to have an effect on afferent (sensory) neurons independent of its action on muscle tone and secretory glands at the periphery.In human studies, the use of BoNT-A has proven to reduce the severity and intensity of attacks in chronic tension type headaches and chronic neck pain. The PREEMPT study concluded that BoNT-A could be used as a preventive therapy in chronic migraine patients and FDA approval was obtained. According to the International Association for the Study of Pain (IASP), BoNT-A is recommended for the management of peripheral neuropathic pain with subcutaneous administration of 50-200 units (50-200U) to onabotulinum toxin A to the painful neuropathic area every 3 months as a third line of treatment. To our knowledge, there are no clinical trials published investigating the effect of intraoral administration of BoNT-A in continuous dentoalveolar neuropathic pain. The aim of this pilot study is to investigate the potential therapeutic effect of intraoral administration of BoNT-A in patients suffering from continuous neuropathic pain.

HYPOTHESIS:

There will be statistically significant differences in reported pain intensity after the intraoral administration of BOTOX® in patients suffering from chronic continuous dentoalveolar neuropathic pain.

A single subject experiment will be conducted with 10 patients where 50 U of BonT-A will be injected into the painful dentoalveolar area. Eligible subjects will complete a pain diary indicating their pain intensity by means of a visual analog scale during one month to establish a baseline. After the first injection, subjects will continue to monitor the VAS daily for 3 months and the infiltration will be repeated a second time following the same protocol. Patient's response will be monitored with the daily pain diary.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• History of continuous dentoalveolar pain with clinically evident positive (hyperalgesia, allodynia) and/or negative (hypoaesthesia, hypoalgesia) signs of trigeminal nerve dysfunction and where other possible pain sources have been ruled out.

• Intractable pain to conventional oral and/or topical pharmacotherapy for neuropathic pain according to the recommendations published by NeuPSIG (Neuropathic Pain Special Interest Group) including anticonvulsants, SNRIs (serotonin and norepinephrine reuptake inhibitors) and/or tricyclic antidepressants.

• Subject consent to participate in the study.

Exclusion Criteria:

• hypersensitive to any onabotulinum toxin preparation or any component in the formulation.

• systemic nerve or muscle disorders

• bleeding disorders

• dysphagia

• breathing problems

• pregnancy or breastfeeding

• previous treatment with botulinum toxin in the last 4 months.

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain

Intervention

Drug:
• onabotulinum toxin A
Each subject will receive 50 units (50 U) of BoNT-A constituted in 1 mL of saline solution injected intraorally to the painful area divided in at least 3 sites, 0.5 to 1.0 cm apart depending on the size of the painful area and following a checkerboard pattern.

Locations

Country	Name	City	State
United States	Orofacial Pain Center	Lexington	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Isabel Moreno Hay	Allergan Sales, LLC

Country where clinical trial is conducted

United States, 

References & Publications (13)

Bach-Rojecky L, Lackovic Z. Antinociceptive effect of botulinum toxin type a in rat model of carrageenan and capsaicin induced pain. Croat Med J. 2005 Apr;46(2):201-8. — View Citation

Bach-Rojecky L, Relja M, Lackovic Z. Botulinum toxin type A in experimental neuropathic pain. J Neural Transm (Vienna). 2005 Feb;112(2):215-9. doi: 10.1007/s00702-004-0265-1. — View Citation

Bach-Rojecky L, Salkovic-Petrisic M, Lackovic Z. Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: bilateral effect after unilateral injection. Eur J Pharmacol. 2010 May 10;633(1-3):10-4. doi: 10.1016/j.ejphar.2010.01.020. Epub 2010 Feb 1. — View Citation

Cui M, Khanijou S, Rubino J, Aoki KR. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain. 2004 Jan;107(1-2):125-33. doi: 10.1016/j.pain.2003.10.008. — View Citation

Dodick DW, Turkel CC, DeGryse RE, Aurora SK, Silberstein SD, Lipton RB, Diener HC, Brin MF; PREEMPT Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache. 2010 Jun;50(6):921-36. doi: 10.1111/j.1526-4610.2010.01678.x. Epub 2010 May 7. — View Citation

Dolly JO, O'Connell MA. Neurotherapeutics to inhibit exocytosis from sensory neurons for the control of chronic pain. Curr Opin Pharmacol. 2012 Feb;12(1):100-8. doi: 10.1016/j.coph.2011.11.001. Epub 2011 Dec 19. — View Citation

Filipovic B, Bach-Rojecky L, Lackovic Z. Lasting reduction of postsurgical hyperalgesia after single injection of botulinum toxin type A in rat. Fundam Clin Pharmacol. 2010 Feb;24(1):43-5. doi: 10.1111/j.1472-8206.2009.00767.x. Epub 2009 Aug 14. — View Citation

Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015 Feb;14(2):162-73. doi: 10.1016/S1474-4422(14)70251-0. Epub 2015 Jan 7. — View Citation

Luvisetto S, Marinelli S, Lucchetti F, Marchi F, Cobianchi S, Rossetto O, Montecucco C, Pavone F. Botulinum neurotoxins and formalin-induced pain: central vs. peripheral effects in mice. Brain Res. 2006 Apr 12;1082(1):124-31. doi: 10.1016/j.brainres.2006.01.117. Epub 2006 Mar 9. — View Citation

Marinelli S, Luvisetto S, Cobianchi S, Makuch W, Obara I, Mezzaroma E, Caruso M, Straface E, Przewlocka B, Pavone F. Botulinum neurotoxin type A counteracts neuropathic pain and facilitates functional recovery after peripheral nerve injury in animal models. Neuroscience. 2010 Nov 24;171(1):316-28. doi: 10.1016/j.neuroscience.2010.08.067. Epub 2010 Sep 6. — View Citation

Miller D, Richardson D, Eisa M, Bajwa RJ, Jabbari B. Botulinum neurotoxin-A for treatment of refractory neck pain: a randomized, double-blind study. Pain Med. 2009 Sep;10(6):1012-7. doi: 10.1111/j.1526-4637.2009.00658.x. Epub 2009 Jul 6. — View Citation

Park HJ, Lee Y, Lee J, Park C, Moon DE. The effects of botulinum toxin A on mechanical and cold allodynia in a rat model of neuropathic pain. Can J Anaesth. 2006 May;53(5):470-7. doi: 10.1007/BF03022619. — View Citation

Relja M, Telarovic S. Botulinum toxin in tension-type headache. J Neurol. 2004 Feb;251 Suppl 1:I12-4. doi: 10.1007/s00415-004-1104-x. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain Intensity	Patient will record the pain intensity by means of a visual analogue scale (VAS, from 0-10 being 0 no pain and 10 the worst possible pain)	Over 7 months