<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02202070</url>
  </required_header>
  <id_info>
    <org_study_id>AAHEJB</org_study_id>
    <nct_id>NCT02202070</nct_id>
  </id_info>
  <brief_title>Botox for Treatment of TMJ Disorder With Bruxism</brief_title>
  <acronym>TMJ</acronym>
  <official_title>Phase 1 Study of Role of Botox in Myofascial Temporomandibular Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hypothesis: Myofascial temporomandibular joint disorder and related symptoms are associated&#xD;
      with mandibular condyle and temporal fossa overloading secondary to temporalis and masseter&#xD;
      muscle hyperactivity and spasm&#xD;
&#xD;
      This study will examine the use of onabotulinumtoxinA (Botox) to treat myofascial pain&#xD;
      disorder in patients with bruxism who frequently exhibit signs of temporomandibular joint&#xD;
      disorder (TMD) in a double blind cross-over randomized clinical trial by injecting 50 units&#xD;
      Botox in temporalis and masseter muscles in 32 patients with 6 months follow up.&#xD;
&#xD;
      The objective of the proposed study will be to establish the safety and efficacy of botox in&#xD;
      treating TMD associated with bruxism. By the time patients reach the specialists office, most&#xD;
      have failed maximal conservative therapies, including non-chew diet, night guard, oral&#xD;
      analgesics, muscle relaxants, physical therapy, and a portion have even undergone more&#xD;
      invasive procedures, such as manipulation under anesthesia, arthroscopy, and arthroplasty&#xD;
      surgeries with limited improvement or recurrence. Primary outcome of the study will be 50%&#xD;
      reduction in pain. Secondary outcomes will be 50% reduction in surgical therapy, 25% increase&#xD;
      in maximal inter-incisal opening (MIO). The investigators look forward to working with you on&#xD;
      the proposed study&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will enroll 32 patients with myofascial TMD. Patient will be aged 18-65. Exclusion&#xD;
      criteria will include neuromuscular diseases, prior botox injections within previous 12&#xD;
      months, pregnancy, and fibromyalgia. All patients will be selected from the outpatient&#xD;
      clinic, complaining of TMJ disease associated with bruxism. Screening will include a thorough&#xD;
      history and exam, and TMJ CT scan or MRI. Patients with neuromuscular disorders,&#xD;
      musculoskeletal disorders, and prior Botox injections will be excluded. Patients who have not&#xD;
      already undergone conservative treatment will be managed with 3 months conservative therapies&#xD;
      prior to becoming eligible. All patients will be informed and consented for participation in&#xD;
      the study and Botox injections. Baseline pain questionnaire, physical exam will be performed.&#xD;
      Patients will be randomized to receive normal saline or botox injections. All patients will&#xD;
      crossover for the second set of injections at 3 months. All patients will receive up to a&#xD;
      total of 200 Botox units at either 0 or 3 month time points. In this regard, patients will&#xD;
      act as their own placebo control. Botox will be prepared according to the manufacturer's&#xD;
      instructions. Briefly, the lyophilized protein will be reconstituted with preservative-free&#xD;
      normal saline and drawn into 1-mL syringe. While the patient is sitting in the office&#xD;
      procedure chair, 25 to 50 U of Botox will be injected into each temporalis muscle and 25 to&#xD;
      50 U of Botox will be injected into the each masseter muscle. The patient will be instructed&#xD;
      to keep head elevated for 8 hours. Patients will be called 3 times after the first round of&#xD;
      injections, to monitor for adverse events. Patients will be seen in clinic at 3 months and&#xD;
      asked to fill out a second pain questionnaire. They will also undergo second physical exam,&#xD;
      and then receive a second set of injections (crossover). Patients will be seen in clinic at 6&#xD;
      months and asked to fill out a third pain questionnaire undergo third physical exam. Patients&#xD;
      will be called 3 times after the second round of injections, to monitor for adverse events.&#xD;
      Patients will be seen in clinic at 6 months and asked to fill out a third pain questionnaire&#xD;
      undergo a third physical exam&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Funding&#xD;
  </why_stopped>
  <start_date type="Actual">January 2015</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>50% reduction in pain</measure>
    <time_frame>6 months</time_frame>
    <description>Patients will be seen in clinic every 3 months and asked to fill out questionaire. Questionaire will include with visual analogue scale (VAS) average pain over previous week, month</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>25% increase in maximal opening at incisors</measure>
    <time_frame>6 months</time_frame>
    <description>Patients will be seen in clinic every 3 months. Providers will objectively measure maximal opening at incisors (MOI), lateral and anterior mandible excursion on clinical exam.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>50% reduction in progression of disease to surgery</measure>
    <time_frame>6 months</time_frame>
    <description>Patients will be monitored for TMJ arthoscopic and arthoplasty procedures</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Temporomandibular Joint Disorders</condition>
  <condition>Bruxism</condition>
  <condition>Temporomandibular Joint Dysfunction Syndrome</condition>
  <condition>Myofascial Pain Dysfunction Syndrome, Temporomandibular Joint</condition>
  <arm_group>
    <arm_group_label>Botox injection first, followed by placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 units Botox injection in masseter and temporalis muscles in the first 3 months, then second injection of normal saline at placebo in second 3 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo injection first, followed Botox</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Injection of normal saline at placebo in first 3 months, then 50 units Botox injection in masseter and temporalis muscles in the second 3 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>onabotulinumtoxinA</intervention_name>
    <arm_group_label>Botox injection first, followed by placebo</arm_group_label>
    <arm_group_label>Placebo injection first, followed Botox</arm_group_label>
    <other_name>BOTOX</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  aged 18-65 persons with a diagnosis of myofascial temporomandibular joint disorder&#xD;
             refractory to conservative treatment for 6 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  rheumatoid arthritis&#xD;
&#xD;
          -  ankylosing spondylitis&#xD;
&#xD;
          -  psoriatic arthritis&#xD;
&#xD;
          -  fibromyalgia&#xD;
&#xD;
          -  neuropathic pain&#xD;
&#xD;
          -  pain of dental origin&#xD;
&#xD;
          -  muscle relaxant use&#xD;
&#xD;
          -  aminoglycoside use&#xD;
&#xD;
          -  prior Botox use&#xD;
&#xD;
          -  neuropathic pain&#xD;
&#xD;
          -  trigeminal neuralgia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alan A Harvey, DMD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistant Professor, Department of Otolaryngology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <last_update_submitted>January 21, 2018</last_update_submitted>
  <last_update_submitted_qc>January 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Washington University School of Medicine</investigator_affiliation>
    <investigator_full_name>Ethan Baughman</investigator_full_name>
    <investigator_title>Plastic surgery resident physician</investigator_title>
  </responsible_party>
  <keyword>onabotulinumtoxinA</keyword>
  <keyword>Temporomandibular Joint Disorders</keyword>
  <keyword>Bruxism</keyword>
  <keyword>Temporomandibular Joint Dysfunction Syndrome</keyword>
  <keyword>Myofascial Pain Dysfunction Syndrome, Temporomandibular Joint</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Joint Diseases</mesh_term>
    <mesh_term>Temporomandibular Joint Disorders</mesh_term>
    <mesh_term>Temporomandibular Joint Dysfunction Syndrome</mesh_term>
    <mesh_term>Fibromyalgia</mesh_term>
    <mesh_term>Myofascial Pain Syndromes</mesh_term>
    <mesh_term>Bruxism</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulinum Toxins, Type A</mesh_term>
    <mesh_term>abobotulinumtoxinA</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02202070
org study id: AAHEJB
nct id: NCT02202070
lead sponsor: 
has dmc: Yes
Hypothesis: Myofascial temporomandibular joint disorder and related symptoms are associated
      with mandibular condyle and temporal fossa overloading secondary to temporalis and masseter
      muscle hyperactivity and spasm

      This study will examine the use of onabotulinumtoxinA (Botox) to treat myofascial pain
      disorder in patients with bruxism who frequently exhibit signs of temporomandibular joint
      disorder (TMD) in a double blind cross-over randomized clinical trial by injecting 50 units
      Botox in temporalis and masseter muscles in 32 patients with 6 months follow up.

      The objective of the proposed study will be to establish the safety and efficacy of botox in
      treating TMD associated with bruxism. By the time patients reach the specialists office, most
      have failed maximal conservative therapies, including non-chew diet, night guard, oral
      analgesics, muscle relaxants, physical therapy, and a portion have even undergone more
      invasive procedures, such as manipulation under anesthesia, arthroscopy, and arthroplasty
      surgeries with limited improvement or recurrence. Primary outcome of the study will be 50%
      reduction in pain. Secondary outcomes will be 50% reduction in surgical therapy, 25% increase
      in maximal inter-incisal opening (MIO). The investigators look forward to working with you on
      the proposed study
The study will enroll 32 patients with myofascial TMD. Patient will be aged 18-65. Exclusion
      criteria will include neuromuscular diseases, prior botox injections within previous 12
      months, pregnancy, and fibromyalgia. All patients will be selected from the outpatient
      clinic, complaining of TMJ disease associated with bruxism. Screening will include a thorough
      history and exam, and TMJ CT scan or MRI. Patients with neuromuscular disorders,
      musculoskeletal disorders, and prior Botox injections will be excluded. Patients who have not
      already undergone conservative treatment will be managed with 3 months conservative therapies
      prior to becoming eligible. All patients will be informed and consented for participation in
      the study and Botox injections. Baseline pain questionnaire, physical exam will be performed.
      Patients will be randomized to receive normal saline or botox injections. All patients will
      crossover for the second set of injections at 3 months. All patients will receive up to a
      total of 200 Botox units at either 0 or 3 month time points. In this regard, patients will
      act as their own placebo control. Botox will be prepared according to the manufacturer's
      instructions. Briefly, the lyophilized protein will be reconstituted with preservative-free
      normal saline and drawn into 1-mL syringe. While the patient is sitting in the office
      procedure chair, 25 to 50 U of Botox will be injected into each temporalis muscle and 25 to
      50 U of Botox will be injected into the each masseter muscle. The patient will be instructed
      to keep head elevated for 8 hours. Patients will be called 3 times after the first round of
      injections, to monitor for adverse events. Patients will be seen in clinic at 3 months and
      asked to fill out a second pain questionnaire. They will also undergo second physical exam,
      and then receive a second set of injections (crossover). Patients will be seen in clinic at 6
      months and asked to fill out a third pain questionnaire undergo third physical exam. Patients
      will be called 3 times after the second round of injections, to monitor for adverse events.
      Patients will be seen in clinic at 6 months and asked to fill out a third pain questionnaire
      undergo a third physical exam
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: 50% reduction in pain
time frame: 6 months
description: Patients will be seen in clinic every 3 months and asked to fill out questionaire. Questionaire will include with visual analogue scale (VAS) average pain over previous week, month
measure: 25% increase in maximal opening at incisors
time frame: 6 months
description: Patients will be seen in clinic every 3 months. Providers will objectively measure maximal opening at incisors (MOI), lateral and anterior mandible excursion on clinical exam.
measure: 50% reduction in progression of disease to surgery
time frame: 6 months
description: Patients will be monitored for TMJ arthoscopic and arthoplasty procedures
arm group label: Botox injection first, followed by placebo
arm group type: Experimental
description: 50 units Botox injection in masseter and temporalis muscles in the first 3 months, then second injection of normal saline at placebo in second 3 months
arm group label: Placebo injection first, followed Botox
arm group type: Experimental
description: Injection of normal saline at placebo in first 3 months, then 50 units Botox injection in masseter and temporalis muscles in the second 3 months.
intervention type: Drug
intervention name: onabotulinumtoxinA
arm group label: Botox injection first, followed by placebo
arm group label: Placebo injection first, followed Botox
other name: BOTOX
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Alan A Harvey, DMD
role: Principal Investigator
affiliation: Assistant Professor, Department of Otolaryngology
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Washington University School of Medicine
investigator full name: Ethan Baughman
investigator title: Plastic surgery resident physician
mesh term: Joint Diseases
mesh term: Temporomandibular Joint Disorders
mesh term: Temporomandibular Joint Dysfunction Syndrome
mesh term: Fibromyalgia
mesh term: Myofascial Pain Syndromes
mesh term: Bruxism
mesh term: Syndrome
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA