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Treatment of Temporo-Myofascial Disorder of Muscular Origin Using Botulinum Toxin: A Prospective Study

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ClinicalTrials.gov Identifier: NCT02810015
Recruitment Status : Unknown
Verified June 2016 by University of Manitoba.
Recruitment status was:  Not yet recruiting
First Posted : June 22, 2016
Last Update Posted : June 22, 2016
Sponsor:
Information provided by (Responsible Party):
University of Manitoba

Tracking Information
First Submitted Date  ICMJE June 20, 2016
First Posted Date  ICMJE June 22, 2016
Last Update Posted Date June 22, 2016
Study Start Date  ICMJE July 2016
Estimated Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2016)
  • Pain (Visual Analog Scale) [ Time Frame: 3 months ]
    Subjective pain scores will be assessed on a visual analog scale (VAS) where 0 is no pain and 10 is the worst facial or jaw pain they've ever experience. Subjective functional assessments will also be assessed with VAS where 0 means no limitation and 10 indicates severe limitation with scales for chewing, drinking, exercising, eating hard food, eating soft food, smiling or laughing, cleaning their teeth, yawning, swallowing and talking.
  • Range of Motion [ Time Frame: 3 months ]
    Range of motion will be assessed with a Boley gauge between the same upper and lower incisor each time
  • Palpation tenderness [ Time Frame: 3 months ]
    Pain to pressure will be ranked from 0 to 5, with 0 indicating no pain and 5 representing extreme debilitating pain. Addition of each score will give a composite score of the overall facial tenderness out of a maximal score of 24 (2 areas X 6 scores X bilaterally).
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2016)
Facial Width [ Time Frame: 3 months ]
A point inferior to each ear lobule bilaterally will be marked as well as a point on the menton will be chosen and recorded. The distance unilaterally from one lobule to menton will be measured for left and right sides and a total distance will also be calculated to assess facial width.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment of Temporo-Myofascial Disorder of Muscular Origin Using Botulinum Toxin: A Prospective Study
Official Title  ICMJE Treatment of Temporo-Myofascial Disorder of Muscular Origin Using Botulinum Toxin: A Prospective Study
Brief Summary Temporomandibular disorders (TMD) are a group of conditions involving the temporomandibular joint (TMJ), masticatory muscles and associated structures. This broad complex of functional disorders often affects the face and jaws causing chronic pain, earaches, headaches, migraines, neck pain, and dysfunction in many people. Patients that do not find benefit with conservative management require surgical intervention. Recently, the use of botulinum toxin has proven effective and has the potential to bridge the gap between conservative therapy and surgical management resulting in less patients requiring invasive surgery. Objective: We aim to treat TMD of muscular origin using Botulinum toxin injections in the trigger points. Methods: Patients, whose pain originates from trigger points, will be enrolled in this prospective trial. This study will evaluate subjective and objective responses to treatment with botulinum toxin. The pair of masticatory muscles, masseter and temporalis, will be injected with 30 units and 20 units of botulinum toxin, respectively. Subjective outcomes such as pain and orofacial function on a visual analog scale as well as objective outcomes such as maximal interincisal mouth opening, tenderness to palpation to the temporalis and masseter muscles, maximal bite force measured by electromyogram and the reduction in muscle bulk due to muscle disuse atrophy will be assessed. Expected Results: We expect trigger points in these patients to disappear and the associated muscles to become partially paralyzed and relaxed. Consequently, we expect that the TMJ loading will be reduced and that the patient's overall functional ability will increase. We also expect that muscular hypertrophy volume from hyperactivity will decrease due to disuse atrophy and impact their cosmetic image positively. Overall, we hope these changes will result in a reduction in pain and headaches which will consequently improve the participant's diet, nutrition, psychological well being and quality of life.
Detailed Description

Introduction Temporomandibular disorders (TMD) are a group of conditions involving the temporomandibular joint (TMJ), masticatory muscles and associated structures. This broad complex of functional disorders often affects the face and jaws causing chronic pain, earaches, headaches, migraines, neck pain, and dysfunction in many people 1,2,3,4,5,6. Conservative treatment for TMD is similar to that of other musculoskeletal conditions. Pharmacologic therapy includes the use of anti-inflammatory medications, muscle relaxants, or opioid analgesics7,8,9,10. Physical treatments comprise of dental splints, directed physiotherapy, moist heat therapy, soft diet, massage and acupuncture11,12,13,14,15,16,17,18,19,20,21,22,23,24,25. At the extreme end of the spectrum, surgical management includes arthrocentesis, arthroscopy and open joint procedures26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44. Some patients can find relief with a combination of these previously mentioned interventions; however, none of these have been proven to be consistently effective. Open joint procedures are not reversible while anti-inflammatory medications and narcotics can have undesirable side effects on the gastrointestinal and central nervous system, respectively. Furthermore, many patients suffering from severe chronic pain do not feel relief with even the strongest narcotic analgesics45,46.

TMD has a complex etiology consisting of components from internal derangement of the joint, arthralgia and/or a component of myofascial pain and muscle hyperactivity1,2,3,4. A treatment that has high specificity and low side effects directed solely at the muscular aspect, which presents with signs and symptoms of trigger points, clenching, and bruxism, could produce another avenue of intervention with significant potential. Recently, the use of botulinum toxin has proven effective and has the potential to be such an agent for treatment with patients suffering from TMD and other orofacial pain conditions47,48,49,50,51,52,53,54,55.

Botulinum toxins are exotoxins derived from Clostridium botulinum, a gram-positive, anaerobic, spore-forming organism. There are 8 different subtypes; type A (BTX-A) has been used in recent studies for the treatment of motor disorders such as cervical dystonia or the hyperactive muscular component of TMD53,54,55. The specific method of action of botulinum toxin is on peripheral synapses. In the synaptic cleft, the botulinum toxin is brought into the presynaptic cell by endocytosis. It acts by blocking the calcium induced release of acetylcholine by selective proteolysis of synaptomal-associated proteins (SNAP)47,48,4,50,51,52,53,54,55. Inhibition of acytelcholine thus causes an inhibition of muscular hyperactivity.

Botulinum toxin has a number of indications approved by the Food and Drug Administration such as the therapeutic treatment for cervical dystonia, cosmetic use such as glabellar lines and wide spectrum of off-label uses such as extracervical spasticities, cerebral palsy, post stroke spasticity, neurologic, dermatologic, and gastrointestinal disorders56. Off-label use of a licensed drug or biologic product occurs with a wide range of products57,58,59.

Objective of the Study We aim to treat TMD of muscular origin using Botulinum toxin injections in the trigger points.

Method Our study will enroll selective patients attending the Oral and Maxillofacial Surgery clinic at the Health Sciences Center and at the University of Manitoba College of Dentistry over a 2-year period. Subjects will be recruited from referrals coming to the Health Sciences Center and College of Dentistry. The design will be prospective study following subjective outcomes such as pain and orofacial function on a visual analog scale as well as objective outcomes such as maximal interincisal mouth opening, tenderness to palpation to the temporalis and masseter muscles, maximal bite force measured by electromyogram and the reduction in muscle bulk due to muscle disuse atrophy. These outcomes have an appreciable affect on the patient's quality of life and provide subjective and objective measurements for analysis and study.

Inclusion criteria for patient's enrolled in this study include: participant's with trigger points in their masticatory muscles including, but not limited to: masseter and temporalis either bilateral or unilateral and secondly, have tried conservative management for at least 3 months and have shown to be refractory to these interventions. Exclusion criteria include: participant's that do not satisfy the inclusion criteria, currently are breastfeeding or pregnant, participant's whose TMD is not muscular in origin, inability to speak or understand English, the inability to provide meaningful informed consent due to physical, cognitive or psychiatric disability, a previous known allergy to Botulinum toxin, multiple sclerosis, pre-existing neuromuscular disorders, Lambert-Eaton syndrome, or chronic centrally mediated neuralgic pain patients.

Before enrollment, informed consent will be obtained from each patient. Informed consent will consist of a thorough initial evaluation and interview. If the patient is assessed to be appropriate for the study the patient will be informed of all risks and potential consequences of the study. Additional information will be given regarding benefits, cost and time required. During the informed consent, the principal investigator and at least one supervisor will be in attendance to answer any questions. Patients will be allowed time to think about their decision and discuss with family members and their family physician. A future appointment can be made to obtain consent and will be witnessed by the principal investigator, a supervisor and an OMFS assistant that has no connection with the study.

On the initial assessment, multiple measurements will be taken (see clinical assessment form attached). Additionally, an appointment will be made for the patient to have their maximal bite force registered pre-injection with the use of EMG.

BTX-A will be reconstituted as directed by the manufacturer. 2.5 mL of diluent (0.9% Saline) per 100 U vial will be used to reconstitute the solution while swirling. This creates a solution with a concentration of 4 U/0.1 mL. Patients will be seated and all usual precautions of sterility and skin preparation will be completed (i.e. alcohol wipes) Injections will be administered unilateral and/or bilaterally in accordance with the topography of the corresponding muscles (temporalis and masseter) into areas of maximal tenderness and pain. Plastic single use insulin syringes with 30 gauge needles will be used to inject 30 U intramuscularly into each masseter, divided evenly into 5 sites and 20 U will be injected into each temporalis, divided evenly over 5 sites. Injections will be completed by the principal investigator and supervisors who will be trained in botulinum toxin injections.

Patients will have scheduled follow ups at 1 week, 1 month, 3 months and 6 months post-injection. An additional follow up call will be made the next day after injection. The clinical assessment form will be used by the principal investigator to take measurements at each follow up appointment, except EMG readings which will only be done at the initial assessment and 3 month follow up appointment. This will provide a total of 5 assessments (including the initial assessment). During this time period, patients will be asked to stop any treatment for their TMD other than analgesics as required.

Subjective pain scores will be assessed on a visual analog scale (VAS) where 0 is no pain and 10 is the worst facial or jaw pain they've ever experience. Subjective functional assessments will also be assessed with VAS where 0 means no limitation and 10 indicates severe limitation with scales for chewing, drinking, exercising, eating hard food, eating soft food, smiling or laughing, cleaning their teeth, yawning, swallowing and talking. Objectively, range of motion will be assessed with a Boley gauge between the same upper and lower incisor each time. Palpation tenderness will be objectively assessed in bilateral temporalis and masseter muscles. Pain to pressure will be ranked from 0 to 5, with 0 indicating no pain and 5 representing extreme debilitating pain. Addition of each score will give a composite score of the overall facial tenderness out of a maximal score of 24 (2 areas X 6 scores X bilaterally). All assessments will be completed by the same examiner every time at the same time of day. Lastly, a measurement of the facial width will be taken. A point inferior to each ear lobule bilaterally will be marked as well as a point on the menton will be chosen and recorded. The distance unilaterally from one lobule to menton will be measured for left and right sides and a total distance will also be calculated to assess facial width. This will be used to determine the cosmetic change due to disuse atrophy 60.

Side effects may include, but are not limited to: transient facial asymmetry during dynamic movements, dysphagia, ptosis, erythematous discoloration or edema at the injection site, rash, and difficulty chewing hard food 61. Every attempt will be made to insure injection of the botulinum in the appropriate site. Aspiration before each injection will help prevent any intravascular and systemic effects while proper patient positioning and proper site identification will help prevent unwanted side effects such as ptosis. If a rash develops, Benadryl will be the first line medication given immediately followed by a several day course of Benadryl at home. In the case of an emergent reaction, adequate management would be undertaken at the clinic and referral to an appropriate service if necessary. Due to passage across the placenta, the use during pregnancy is also contraindicated. All patient's who are currently breastfeeding or pregnant will be excluded from the study62.

Funding for the study will be provided by application to research grants through The University of Manitoba and the Canadian Association of Oral and Maxillofacial Surgeons.

Anticipated results We expect trigger points in these patients to disappear and the associated muscles to become partially paralyzed and relaxed. Consequently, we expect that the TMJ loading will be reduced and that the patient's overall functional ability will increase. We also expect that muscular hypertrophy volume from hyperactivity will decrease due to disuse atrophy and impact their cosmetic image positively. Overall, we hope these changes will result in a reduction in pain and headaches which will consequently improve the participant's diet, nutrition, psychological well being and quality of life.

We expect this study will be published in the International Journal of Oral and Maxillofacial Surgery and that results will be presented at the International meeting of Oral and Maxillofacial Surgeons in 2018.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Temporo-Myofascial Disorder
Intervention  ICMJE Drug: Botulinum Toxin Type A
BTX-A will be reconstituted as directed by the manufacturer. 2.5 mL of diluent (0.9% Saline) per 100 U vial will be used to reconstitute the solution while swirling. This creates a solution with a concentration of 4 U/0.1 mL. Patients will be seated and all usual precautions of sterility and skin preparation will be completed (i.e. alcohol wipes) Injections will be administered unilateral and/or bilaterally in accordance with the topography of the corresponding muscles (temporalis and masseter) into areas of maximal tenderness and pain. Plastic single use insulin syringes with 30 gauge needles will be used to inject 30 U intramuscularly into each masseter, divided evenly into 5 sites and 20 U will be injected into each temporalis, divided evenly over 5 sites. Injections will be completed by the principal investigator and supervisors who will be trained in botulinum toxin injections.
Study Arms  ICMJE Experimental: Botulinum Toxin A
BTX-A will be reconstituted as directed by the manufacturer. 2.5 mL of diluent (0.9% Saline) per 100 U vial will be used to reconstitute the solution while swirling. This creates a solution with a concentration of 4 U/0.1 mL. Patients will be seated and all usual precautions of sterility and skin preparation will be completed (i.e. alcohol wipes) Injections will be administered unilateral and/or bilaterally in accordance with the topography of the corresponding muscles (temporalis and masseter) into areas of maximal tenderness and pain. Plastic single use insulin syringes with 30 gauge needles will be used to inject 30 U intramuscularly into each masseter, divided evenly into 5 sites and 20 U will be injected into each temporalis, divided evenly over 5 sites. Injections will be completed by the principal investigator and supervisors who will be trained in botulinum toxin injections.
Intervention: Drug: Botulinum Toxin Type A
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 20, 2016)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2019
Estimated Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant's with trigger points in their masticatory muscles including, but not limited to: masseter and temporalis either bilateral or unilateral and secondly
  • have tried conservative management for at least 3 months and have shown to be refractory to these interventions.

Exclusion Criteria:

  • participant's that do not satisfy the inclusion criteria
  • currently are breastfeeding or pregnant
  • participant's whose TMD is not muscular in origin
  • inability to speak or understand English
  • the inability to provide meaningful informed consent due to physical, cognitive or psychiatric disability
  • a previous known allergy to Botulinum toxin
  • multiple sclerosis
  • pre-existing neuromuscular disorders
  • Lambert-Eaton syndrome
  • chronic centrally mediated neuralgic pain patients.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02810015
Other Study ID Numbers  ICMJE B2016:027
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Manitoba
Study Sponsor  ICMJE University of Manitoba
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Reda Elgazzar, DMD University of Manitoba
PRS Account University of Manitoba
Verification Date June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP