Bruxism Xeomin® Intervention Trial (BRUX-XIT)

Effects of Botulinum Toxin Type A (Xeomin®) Injections Into Bilateral Masseter Muscles for Management of Bruxism and Associated Symptoms: Single Center Open Label Longitudinal Pilot Study

The purpose of this study is to test whether severe masticatory muscle spasms during sleep (e.g. teeth clenching and grinding, known as "bruxism" in technical jargon) demonstrably decrease after application of botulinum toxin type A (Xeomin®). Xeomin® has so far been used to relieve spasms of other muscles and is an approved drug in Switzerland. This study is now intended to test the suitability of this drug for relaxation of the masseter muscle.

Study Overview

• Status: Not yet recruiting
• Conditions: Sleep Bruxism, Adult
• Intervention / Treatment: Drug: Incobotulinumtoxin A (BTX A) Xeomin®

Detailed Description

Bruxism is a prevalent condition that differentially burdens individuals. The overall objective of this pilot study is to measure the effects of BTX-A (Xeomin®) injections into bilateral masseter muscles for the management of sleep bruxism and associated symptoms. The hypothesis is that BTX-A reduces masticatory muscle activity. The aim of this study is to instrumentally monitor subjects closely over an extended time period of three months before and after application of BTX-A.

Botulinum toxin type A ( BTX A; Xeomin ® ) temporarily blocks neuromuscular synapses. It is successfully and safely used therapeutically in various types of movement disorders and in chronic migraineurs. The mechanism of action of this treatment is related to a reduction of neurotransmitter release leading to reduced muscle activity.

The following Null hypothesis will be tested:

Injections of Xeomin® into the masseter muscles bilaterally (25 Units per muscle applied with 2 injections in each muscle) have no effect on bruxism measured by A) Masticatory muscle activity (1° objective) B) Subjects' well-being (2° objective) C) Sensitivity of masticatory muscles and jaw joints (2° objective) D) Anxiety over tooth wear (2° objective) E) Disturbed sleep by bed partner (2° objective)

Following instruments will be used:

1. WISE questionnaires. A comprehensive web-based interdisciplinary symptom evaluation tool.
2. Algometer for sensitivity measure of masticatory muscles and jaw joints.
3. Bio-signal recorder. Parallel to the Electromyography (EMG) of the masseter muscles, other bio-signals such as a number of electroencephalographic (EEG) derivations, electrooculogram (EOG ) as well as an electrocardiogram (ECG) will be recorded, in order to detect sleep stages and better identify bruxism episodes. The device used in this study has been approved for projects NIH #2R01DE016417-05A1 and #1 R01DE028548-01.
4. Ultrasound for masseter muscle thickness measure
5. Dual-color chewing gum for chewing efficiency measure.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dominik A Ettlin, MD, DMD; Phone Number: +41 44 6343254; Email: dominik.ettlin@zzm.uzh.ch

Study Locations

• Switzerland
  • Zurich, Switzerland, 8032
    • University of Zurich, Center of Dental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-90 years;
• patients complaining of bruxism and/or bruxism-related symptoms.
• Sufficient knowledge of German to understand the patient information and the trial arrangement.

Exclusion Criteria:

• Contraindications for Xeomin® treatment such as generalized disorders of muscle activity (myasthenia gravis, Lambert-Eaton-Rooke syndrome);
• documented hypersensitivity to one of the components,
• local infection of the injection sites;
• intake of anticoagulants or muscle relaxing medications;
• recreational drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sleep Bruxism Subjects; Ultrasound guided BTX-A injection: 25 units (divided in two injections) in each masseter muscle. One-time intervention. Effect observation by measuring various biosignals (EMG, EOG, EEG), bite force, chewing efficiency, psychometric assessments.	Drug: Incobotulinumtoxin A (BTX A) Xeomin®; Injections into the masseter muscles bilaterally (25 Units per muscle applied with 2 injections in each muscle)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of maximum EMG amplitudes	Change of average of maximum EMG amplitudes of all bruxism events per night between days 1-14 (baseline) and days 29-42.	days 1-14, days 29-42
Verbal Rating Scale of Global impression of change	Verbal Rating Scale (VRS) containing the following levels "much worse", "slightly worse", "no change", "slightly improved", "much improved" of "global impression of change" at the end of the study (day 154)	day 154

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of maximum EMG amplitude	Change of average of maximum EMG amplitudes of all bruxism events per night between days 1-14 (baseline) and days 15-28, 85-98, and 141-154.	days 1-14, days 15-28, days 85-98, days 141-154
EMG amplitude at maximum voluntary contraction	EMG signal amplitude (RMS) at maximum voluntary contraction (MVC) in [V]	days 1-14, days 15-28, days 85-98, days 141-154
number of masseter contraction episodes per hour (N/h)	number of masseter contraction episodes per hour calculated from EMG signal amplitude normalized on MVC [N/h]	days 1-14, days 15-28, days 85-98, days 141-154
duration of masseter contraction episodes (Dur)	duration of masseter contraction episodes in [sec] calculated from EMG signal amplitude normalized on MVC	days 1-14, days 15-28, days 85-98, days 141-154
EMG-Index	EMG-Index = 0.5 x N/h + Dur	days 1-14, days 15-28, days 85-98, days 141-154
EMG Duty Factor	EMG duty factor = % duration of muscle activity/total recording time	days 1-14, days 15-28, days 85-98, days 141-154
Sensitivity of masticatory muscles and jaw joints	Sensitivity of masticatory muscles and jaw joints in [N]	day 1, 14, 28, 42, 98, 154
Self-report of bruxism	Yes/No answer to direct question	day 1, 14, 28, 42, 98, 154
Numerical Rating Scale masseter muscle pain	Numerical Rating Scale (NRS) (0-10) with 0 = no pain and 10 = worst imaginable pain	day 1, 14, 28, 42, 98, 154
Numerical Rating Scale report of spontaneous facial pain	Numerical Rating Scale (NRS) (0-10) with 0 = no pain and 10 = worst imaginable pain	day 1, 14, 28, 42, 98, 154
Numerical Rating Scale report of jaw movement related facial pain	Numerical Rating Scale (NRS) (0- 10) with 0 = no pain and 10 = worst imaginable pain	day 1, 14, 28, 42, 98, 154
Numerical Rating Scale report of anxiety over tooth wear	Numerical Rating Scale (NRS) (0-10) with 0 = no anxiety and 10 = worst imaginable anxiety	day 1, 14, 28, 42, 98, 154
Numerical Rating Scale disturbed sleep of bed partner	Numerical Rating Scale (NRS) (0-10) with 0 = no disturbed sleep and 10 = worst imaginable sleep	day 1, 14, 28, 42, 98, 154

Collaborators and Investigators

• Sponsor: Dominik Ettlin
• Collaborators: Merz Pharmaceuticals
• Investigators: Principal Investigator: Dominik A Ettlin, MD, DMD, University of Zurich

Publications and helpful links

General Publications

• Ettlin DA, Sommer I, Bronnimann B, Maffioletti S, Scheidt J, Hou MY, Lukic N, Steiger B. Design, construction, and technical implementation of a web-based interdisciplinary symptom evaluation (WISE) - a heuristic proposal for orofacial pain and temporomandibular disorders. J Headache Pain. 2016 Dec;17(1):77. doi: 10.1186/s10194-016-0670-5. Epub 2016 Aug 31.
• Iwasaki LR, Gonzalez YM, Liu H, Marx DB, Gallo LM, Nickel JC. A pilot study of ambulatory masticatory muscle activities in temporomandibular joint disorders diagnostic groups. Orthod Craniofac Res. 2015 Apr;18 Suppl 1(0 1):146-55. doi: 10.1111/ocr.12085.
• Silva LC, Nogueira TE, Rios LF, Schimmel M, Leles CR. Reliability of a two-colour chewing gum test to assess masticatory performance in complete denture wearers. J Oral Rehabil. 2018 Apr;45(4):301-307. doi: 10.1111/joor.12609. Epub 2018 Feb 9.

Helpful Links

• Homepage Company used Medical Device Algomed

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: March 2, 2021
• First Submitted That Met QC Criteria: March 9, 2021
• First Posted (Actual): March 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 11, 2021
• Last Update Submitted That Met QC Criteria: March 9, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Wake Disorders; Stomatognathic Diseases; Parasomnias; Tooth Diseases; Bruxism; Sleep Bruxism; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; incobotulinumtoxinA
• Other Study ID Numbers: BRUX-XIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No