Clinical trial NCT04792398: Bruxism Xeomin® Intervention Trial
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Sleep Bruxism, Adult
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Merz Pharmaceuticals
First posted: 2021-03-11
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Observational study
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change of maximum EMG amplitudes
timeFrame: days 1-14, days 29-42
measure: Verbal Rating Scale of Global impression of change
timeFrame: day 154
Secondary outcomes:
measure: Change of maximum EMG amplitude
timeFrame: days 1-14, days 15-28, days 85-98, days 141-154
measure: EMG amplitude at maximum voluntary contraction
timeFrame: days 1-14, days 15-28, days 85-98, days 141-154
measure: number of masseter contraction episodes per hour (N/h)
timeFrame: days 1-14, days 15-28, days 85-98, days 141-154
measure: duration of masseter contraction episodes (Dur)
timeFrame: days 1-14, days 15-28, days 85-98, days 141-154
measure: EMG-Index
timeFrame: days 1-14, days 15-28, days 85-98, days 141-154
measure: EMG Duty Factor
timeFrame: days 1-14, days 15-28, days 85-98, days 141-154
measure: Sensitivity of masticatory muscles and jaw joints
timeFrame: day 1, 14, 28, 42, 98, 154
measure: Self-report of bruxism
timeFrame: day 1, 14, 28, 42, 98, 154
measure: Numerical Rating Scale masseter muscle pain
timeFrame: day 1, 14, 28, 42, 98, 154
measure: Numerical Rating Scale report of spontaneous facial pain
timeFrame: day 1, 14, 28, 42, 98, 154
measure: Numerical Rating Scale report of jaw movement related facial pain
timeFrame: day 1, 14, 28, 42, 98, 154
measure: Numerical Rating Scale report of anxiety over tooth wear
timeFrame: day 1, 14, 28, 42, 98, 154
measure: Numerical Rating Scale disturbed sleep of bed partner
timeFrame: day 1, 14, 28, 42, 98, 154
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University of Zurich, Center of Dental Medicine
Study officials:
affiliation: University of Zurich
name: Dominik A Ettlin, MD, DMD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.