Bruxism Xeomin® Intervention Trial

Study Overview
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Brief Summary
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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.

Detailed Description
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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: WISE questionnaires. A comprehensive web-based interdisciplinary symptom evaluation tool. Algometer for sensitivity measure of masticatory muscles and jaw joints. 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. Ultrasound for masseter muscle thickness measure Dual-color chewing gum for chewing efficiency measure.

Official Title
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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

Conditions
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Sleep Bruxism, Adult

Intervention / Treatment
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* Drug: Incobotulinumtoxin A (BTX A) Xeomin®


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Observational study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sleep Bruxism Subjects<br>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®<br>* Injections into the masseter muscles bilaterally (25 Units per muscle applied with 2 injections in each muscle)<br>|

What is the study measuring?
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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 |