<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/NCT04426123</url>
  </required_header>
  <id_info>
    <org_study_id>273697</org_study_id>
    <nct_id>NCT04426123</nct_id>
  </id_info>
  <brief_title>Masseter Myofascial Pain Relief Following an Intra-muscular Injection With Botulinum Toxin Type A.</brief_title>
  <official_title>Masseter Myofascial Pain Relief Following an Intra-muscular Injection With Botulinum Toxin Type A: A Randomized Double-blind Controlled Multicenter Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Region Örebro County</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Region Västmanland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Landstinget i Värmland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Region Örebro County</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Investigating the effect of a single intramuscular injection with botulinum toxin (BTX)&#xD;
      compared to NaCl in patients with jaw muscle myalgia.&#xD;
&#xD;
      This investigation is designed as an double blind multicenter pilot study for hypothesis&#xD;
      generation on 48 patients with chronic jaw muscle myalgia at four specialist dental clinics.&#xD;
      The subjects visit the clinic on 3 predefined occasions, one telephone call and one scheduled&#xD;
      evaluation by mail.&#xD;
&#xD;
      The objective is primarily to evaluate the change in number of days with pain at two months&#xD;
      following one session of BTX injections of the masseter and temporalis muscles in subjects&#xD;
      with jaw muscle myalgia pain.&#xD;
&#xD;
      The outcome of this study will serve as a basis for a later randomized controlled trial&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Temporomandibular disorders (TMD) is the second most common musculoskeletal condition (after&#xD;
      chronic low back pain) and refer to pain and dysfunction in the temporomandibular system and&#xD;
      its muscles, joints, and associated structures. The prevalence of TMD is 4-15% among adults&#xD;
      where myalgia is the most common form of TMD.&#xD;
&#xD;
      Diagnostic Criteria for temporomandibular disorders (DC/TMD) was introduced in 2014 and is&#xD;
      used worldwide for classifying TMD. Myalgia is the second group of disorders of DC/TMD and is&#xD;
      defined by pain in a masticatory structure that is modified by jaw movement, function, or&#xD;
      parafunction and familiar pain in masticatory muscle(s) with either muscle palpation or&#xD;
      maximum opening.&#xD;
&#xD;
      Myofacial pain is the most common form of TMD, affecting about half of the patients&#xD;
      presenting in TMD clinics. Myofascial pain is usually treated with conservative treatment&#xD;
      including occlusal, physical and pharmacologic therapies. However, there is no evidence on&#xD;
      which conservative treatment is the most beneficial in treating myalgia pain, mainly due to&#xD;
      lack of randomized controlled trials.&#xD;
&#xD;
      Botulinum toxin A (BTX) is a neurotoxin isolated from Clostridium botulinum. Injected into a&#xD;
      muscle the effect occurs in the presynaptic junction by blocking the release of&#xD;
      acetylcholine, resulting in weakening of the muscular activity by affecting alpha and gamma&#xD;
      motor neurons. The clinical effect occurs after 3-7 days after administration with a duration&#xD;
      of up to 4 months. The BTX-effect diminish when new formation of synaptic connections occur&#xD;
      due to sprouting.&#xD;
&#xD;
      Regional myofascial pain is characterized by the presence of trigger points and BTX, as a&#xD;
      potent neurotoxin, has been used for its treatment. However, a Cochrane review reported&#xD;
      inconclusive evidence to support the use of BTX in the treatment of myofascial pain. In&#xD;
      another Cochrane review on cervical dystonia significant improvements were found with odds&#xD;
      ratio (OR) of 20% in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score&#xD;
      after four weeks (OR 4.69; 95% CI 2.06 to 10.69) and a weighted mean difference of -5.92 (95%&#xD;
      CI -9.61 to -2.23). Studies investigating the effect of BTX on masticatory muscle myalgia&#xD;
      have been summarized in systematic reviews and with inconclusive evidence to support the&#xD;
      effect of BTX. Meta-analyses were inconclusive due to the heterogeneity of the studies and&#xD;
      methodological flaws.&#xD;
&#xD;
      There are several theories of how BTX may reduce myalgia. Assuming myalgia is caused by&#xD;
      muscle hyperactivity, BTX will reduce hyperactivity and thereby pain. In the presence of&#xD;
      trigger points within the muscle, BTX may eliminate the triggers and then reduce pain. In&#xD;
      case of muscle inflammatory pain, BTX reduces muscle activity and may then facilitate&#xD;
      reduction of inflammation and consequently the pain. This can be caused by blocking the&#xD;
      release of neurotransmitters such as substance P and glutamate. In conclusion, the mechanism&#xD;
      on how muscle paralysis reduces pain is not clear.&#xD;
&#xD;
      A drawback of BTX-treatment is the potential side effects not found for other treatments of&#xD;
      myalgia pain. Minor complications associated with any intra-muscular injection are pain,&#xD;
      bruising and swelling. Some patients develop severe headache, muscle atrophy and paralysis in&#xD;
      areas adjacent to the injection site causing ptos, difficulty in speaking, swallowing and&#xD;
      respiratory problems. The risk-benefit relation is not established when treating masticatory&#xD;
      myalgia.&#xD;
&#xD;
      The National Board of Health and Welfare in Sweden does not recommend the use of BTX for&#xD;
      treating myofascial pain because of insufficient scientific evidence. The key publications on&#xD;
      BTX for the treatment of jaw muscle pain are using reduction of pain intensity as the primary&#xD;
      measure which may be a blunt parameter to evaluate treatment effects of chronic pain.&#xD;
&#xD;
      Therefore, there is a need to explore BTX-treatment effects of jaw muscle myalgia in relation&#xD;
      to side effects using a set of measures to be used for hypothesis generation.&#xD;
&#xD;
      The purpose of this study is to help fill one of the knowledge gaps and be a valuable&#xD;
      addition to increasing the quality of treatments made on the group of people diagnosed with&#xD;
      myalgia in the masticatory system.&#xD;
&#xD;
      This study is targeted to include a total of 48 subjects with the diagnosis myalgia. Half of&#xD;
      the subjects will receive one injection of botulinum toxin type A in their masseter and&#xD;
      temporalis muscles. The other half will be the placebo group receiving NaCl injection on the&#xD;
      same sites.&#xD;
&#xD;
      Injection treatment is made bilaterally independent of the presence of bilateral or&#xD;
      unilateral myalgia.&#xD;
&#xD;
      A randomization list is generated by computer and each randomization should be balanced with&#xD;
      as many subjects in the treatment group as in the control group. Randomization will be made&#xD;
      in blocks of four. The randomization, which is sealed in individual envelopes, is performed&#xD;
      by a person who is not attached to the project and keeps the randomization list locked up.&#xD;
      The envelopes contain the randomization number and description of the substance to be&#xD;
      injected. The envelope is opened immediately before the treatment and after all inclusion&#xD;
      criteria and exclusion criteria are met.&#xD;
&#xD;
      After the investigator has checked alignment to the inclusion/exclusion criteria the study&#xD;
      nurse will prepare the syringes in a separate room according to the randomization envelope&#xD;
      information. The opened randomization envelope will then be put in a larger envelope which&#xD;
      will be sealed and stored in the CRF-binder. The syringes will then be provided to the&#xD;
      investigator without her/his knowledge on its content.&#xD;
&#xD;
      A paper-based Case Report Form (CRF) is used for data collection. The investigator must&#xD;
      ensure that data is registered and any corrections in the CRF are made as stated in the study&#xD;
      protocol and in accordance with the instructions.&#xD;
&#xD;
      The study team at each center consists of a dentist and a study nurse. The subjects visit the&#xD;
      clinic on 3 predefined occasions, one telephone call and one scheduled evaluation by mail.&#xD;
&#xD;
      Visit 1: Enrollment, subject information and informed consent. After checking the inclusion&#xD;
      and exclusion criteria the subject is assigned an enrollment number. Clinical examination is&#xD;
      performed by the dentist. Questionnaires and diaries are handed out and the patient is&#xD;
      instructed.&#xD;
&#xD;
      Visit 2: This visit will be done 2 weeks after enrollment visit. A baseline clinical&#xD;
      examination is done. Questionnaires and diary are returned. After checking the inclusion and&#xD;
      exclusion criteria the intervention substance is prepared according to the randomization code&#xD;
      and the dentist performs the injection treatment. The subject is instructed how to complete a&#xD;
      new set of questionnaires. Adverse events are registered.&#xD;
&#xD;
      By mail evaluation: Two weeks (+ 4 days) after visit 2. The patient returns the&#xD;
      questionnaires and diaries by surface-mail.&#xD;
&#xD;
      Telephone evaluation: One month (+ 1 week) after visit 2. Telephone call. Adverse events are&#xD;
      registered.&#xD;
&#xD;
      Visit 3: Two months (+ 2 weeks) after visit 2. The dentist collects questionnaires and&#xD;
      diaries and a clinical examination is made. The subject is then completed within the scope of&#xD;
      the study. Adverse events are registered. If further treatment is required, it is made&#xD;
      outside the study protocol.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain days</measure>
    <time_frame>2 months</time_frame>
    <description>The change in frequency (number) of pain days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain intensity</measure>
    <time_frame>2 months</time_frame>
    <description>Change in average pain intensity by answering the question: &quot;In the past two weeks&quot;, on the average, how intense was your pain rated on a 0-10 scale where 0 is &quot;no pain&quot; and 10 &quot;pain as bad as could be&quot; (That is, your usual jaw pain at times you were experiencing pain)&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain intensity on maximal opening of the jaw</measure>
    <time_frame>2 months</time_frame>
    <description>Change of pain intensity at maximal opening of the jaw. The subject will assess their jaw pain on maximal opening on a numeric rating scale 0-10, where 0 is no pain and 10 is worst pain imaginable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>JFLS-20</measure>
    <time_frame>2 months</time_frame>
    <description>Change in physical function: Jaw functional problems will be evaluated using the 20-item global Jaw Functional Limitation Scale (JFLS-20), with possible mean scores ranging from 0-10, where 0 i no limitation and 10 is severe limitation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PHQ-9</measure>
    <time_frame>2 months</time_frame>
    <description>Change in emotional function using the Patient Health Questionnaire-9 (PHQ-9), a multipurpose instrument used for screening, diagnosing and measuring depression severity, with possible scores ranging from 0-27, where higher scores indicate more severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PGIC</measure>
    <time_frame>2 months</time_frame>
    <description>Global improvement. At the follow-up visit the subjects will rate the change in their overall status since beginning the study treatment using the Patient Global Impression of Change (PGIC) scale, a 7-point scaled instrument ranging from &quot;very much improved&quot; to &quot;very much worse&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GCPS</measure>
    <time_frame>2 months</time_frame>
    <description>Change in the Graded Chronic Pain Scale, GCPS, pain and its consequences. GCPS assesses 2 dimensions of overall chronic pain severity: pain intensity and pain-related disability. For pain intensity a numeric rating scale 0-10 is used, where 0 is no pain and 10 is worst pain imaginable. For pain-related disability a numeric rating scale from 0-10 is used where 0 is 'no interference' and 10 is 'extreme change'.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Myalgia</condition>
  <condition>Myofascial Pain</condition>
  <arm_group>
    <arm_group_label>Botulinum toxin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Botulinum toxin type A</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline solution</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>NaCl</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Botulinum toxin type A</intervention_name>
    <description>Intramuscular injection with Botulinum toxin type A in m.masseter and m.temporalis.</description>
    <arm_group_label>Botulinum toxin</arm_group_label>
    <other_name>Botox</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>saline solution</intervention_name>
    <description>Intramuscular injection with NaCl in m.masseter and m.temporalis.</description>
    <arm_group_label>Saline solution</arm_group_label>
    <other_name>Physiologic NaCl</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age &gt; 18 years&#xD;
&#xD;
          -  &gt; 3-month complaints of jaw/face pain&#xD;
&#xD;
          -  the diagnose myalgia according to DC/TMD&#xD;
&#xD;
          -  understands Swedish verbally and in writing&#xD;
&#xD;
          -  in writing give his/her consent to participate&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  polyarthritis/connective tissue disease&#xD;
&#xD;
          -  fibromyalgia or other generalized pain&#xD;
&#xD;
          -  neurological disorders&#xD;
&#xD;
          -  whiplash associated disorders&#xD;
&#xD;
          -  ongoing virus or bacterial infection&#xD;
&#xD;
          -  ongoing dental treatment&#xD;
&#xD;
          -  botulinum toxin injection in the jaw or face past six months&#xD;
&#xD;
          -  complex psychiatric/psychological profile, institutional residence&#xD;
&#xD;
          -  employee at the trial clinic, internal resident&#xD;
&#xD;
          -  hypersensitivity to botulinum toxin, human albumin&#xD;
&#xD;
          -  serious health conditions according to the examiner's assessment&#xD;
&#xD;
          -  in the presence of infection at the proposed injection site(s)&#xD;
&#xD;
          -  pregnancy or lactating&#xD;
&#xD;
          -  fertile women not on contraception&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Göran Isacsson, Assoc. Prof.</last_name>
    <role>Study Director</role>
    <affiliation>Stockholm</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mohamad Schumann, DDS</last_name>
    <role>Study Director</role>
    <affiliation>Västerås</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Daniel Ovesson, DDS</last_name>
    <role>Study Director</role>
    <affiliation>Karlstad</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ava Minston, DDS</last_name>
    <phone>+46196024070</phone>
    <email>ava.minston@regionorebrolan.se</email>
  </overall_contact>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 8, 2020</last_update_submitted>
  <last_update_submitted_qc>June 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myofascial Pain Syndromes</mesh_term>
    <mesh_term>Myalgia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulinum Toxins</mesh_term>
    <mesh_term>Botulinum Toxins, Type A</mesh_term>
    <mesh_term>abobotulinumtoxinA</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04426123
org study id: 273697
nct id: NCT04426123
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Investigating the effect of a single intramuscular injection with botulinum toxin (BTX)
      compared to NaCl in patients with jaw muscle myalgia.

      This investigation is designed as an double blind multicenter pilot study for hypothesis
      generation on 48 patients with chronic jaw muscle myalgia at four specialist dental clinics.
      The subjects visit the clinic on 3 predefined occasions, one telephone call and one scheduled
      evaluation by mail.

      The objective is primarily to evaluate the change in number of days with pain at two months
      following one session of BTX injections of the masseter and temporalis muscles in subjects
      with jaw muscle myalgia pain.

      The outcome of this study will serve as a basis for a later randomized controlled trial
Temporomandibular disorders (TMD) is the second most common musculoskeletal condition (after
      chronic low back pain) and refer to pain and dysfunction in the temporomandibular system and
      its muscles, joints, and associated structures. The prevalence of TMD is 4-15% among adults
      where myalgia is the most common form of TMD.

      Diagnostic Criteria for temporomandibular disorders (DC/TMD) was introduced in 2014 and is
      used worldwide for classifying TMD. Myalgia is the second group of disorders of DC/TMD and is
      defined by pain in a masticatory structure that is modified by jaw movement, function, or
      parafunction and familiar pain in masticatory muscle(s) with either muscle palpation or
      maximum opening.

      Myofacial pain is the most common form of TMD, affecting about half of the patients
      presenting in TMD clinics. Myofascial pain is usually treated with conservative treatment
      including occlusal, physical and pharmacologic therapies. However, there is no evidence on
      which conservative treatment is the most beneficial in treating myalgia pain, mainly due to
      lack of randomized controlled trials.

      Botulinum toxin A (BTX) is a neurotoxin isolated from Clostridium botulinum. Injected into a
      muscle the effect occurs in the presynaptic junction by blocking the release of
      acetylcholine, resulting in weakening of the muscular activity by affecting alpha and gamma
      motor neurons. The clinical effect occurs after 3-7 days after administration with a duration
      of up to 4 months. The BTX-effect diminish when new formation of synaptic connections occur
      due to sprouting.

      Regional myofascial pain is characterized by the presence of trigger points and BTX, as a
      potent neurotoxin, has been used for its treatment. However, a Cochrane review reported
      inconclusive evidence to support the use of BTX in the treatment of myofascial pain. In
      another Cochrane review on cervical dystonia significant improvements were found with odds
      ratio (OR) of 20% in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score
      after four weeks (OR 4.69; 95% CI 2.06 to 10.69) and a weighted mean difference of -5.92 (95%
      CI -9.61 to -2.23). Studies investigating the effect of BTX on masticatory muscle myalgia
      have been summarized in systematic reviews and with inconclusive evidence to support the
      effect of BTX. Meta-analyses were inconclusive due to the heterogeneity of the studies and
      methodological flaws.

      There are several theories of how BTX may reduce myalgia. Assuming myalgia is caused by
      muscle hyperactivity, BTX will reduce hyperactivity and thereby pain. In the presence of
      trigger points within the muscle, BTX may eliminate the triggers and then reduce pain. In
      case of muscle inflammatory pain, BTX reduces muscle activity and may then facilitate
      reduction of inflammation and consequently the pain. This can be caused by blocking the
      release of neurotransmitters such as substance P and glutamate. In conclusion, the mechanism
      on how muscle paralysis reduces pain is not clear.

      A drawback of BTX-treatment is the potential side effects not found for other treatments of
      myalgia pain. Minor complications associated with any intra-muscular injection are pain,
      bruising and swelling. Some patients develop severe headache, muscle atrophy and paralysis in
      areas adjacent to the injection site causing ptos, difficulty in speaking, swallowing and
      respiratory problems. The risk-benefit relation is not established when treating masticatory
      myalgia.

      The National Board of Health and Welfare in Sweden does not recommend the use of BTX for
      treating myofascial pain because of insufficient scientific evidence. The key publications on
      BTX for the treatment of jaw muscle pain are using reduction of pain intensity as the primary
      measure which may be a blunt parameter to evaluate treatment effects of chronic pain.

      Therefore, there is a need to explore BTX-treatment effects of jaw muscle myalgia in relation
      to side effects using a set of measures to be used for hypothesis generation.

      The purpose of this study is to help fill one of the knowledge gaps and be a valuable
      addition to increasing the quality of treatments made on the group of people diagnosed with
      myalgia in the masticatory system.

      This study is targeted to include a total of 48 subjects with the diagnosis myalgia. Half of
      the subjects will receive one injection of botulinum toxin type A in their masseter and
      temporalis muscles. The other half will be the placebo group receiving NaCl injection on the
      same sites.

      Injection treatment is made bilaterally independent of the presence of bilateral or
      unilateral myalgia.

      A randomization list is generated by computer and each randomization should be balanced with
      as many subjects in the treatment group as in the control group. Randomization will be made
      in blocks of four. The randomization, which is sealed in individual envelopes, is performed
      by a person who is not attached to the project and keeps the randomization list locked up.
      The envelopes contain the randomization number and description of the substance to be
      injected. The envelope is opened immediately before the treatment and after all inclusion
      criteria and exclusion criteria are met.

      After the investigator has checked alignment to the inclusion/exclusion criteria the study
      nurse will prepare the syringes in a separate room according to the randomization envelope
      information. The opened randomization envelope will then be put in a larger envelope which
      will be sealed and stored in the CRF-binder. The syringes will then be provided to the
      investigator without her/his knowledge on its content.

      A paper-based Case Report Form (CRF) is used for data collection. The investigator must
      ensure that data is registered and any corrections in the CRF are made as stated in the study
      protocol and in accordance with the instructions.

      The study team at each center consists of a dentist and a study nurse. The subjects visit the
      clinic on 3 predefined occasions, one telephone call and one scheduled evaluation by mail.

      Visit 1: Enrollment, subject information and informed consent. After checking the inclusion
      and exclusion criteria the subject is assigned an enrollment number. Clinical examination is
      performed by the dentist. Questionnaires and diaries are handed out and the patient is
      instructed.

      Visit 2: This visit will be done 2 weeks after enrollment visit. A baseline clinical
      examination is done. Questionnaires and diary are returned. After checking the inclusion and
      exclusion criteria the intervention substance is prepared according to the randomization code
      and the dentist performs the injection treatment. The subject is instructed how to complete a
      new set of questionnaires. Adverse events are registered.

      By mail evaluation: Two weeks (+ 4 days) after visit 2. The patient returns the
      questionnaires and diaries by surface-mail.

      Telephone evaluation: One month (+ 1 week) after visit 2. Telephone call. Adverse events are
      registered.

      Visit 3: Two months (+ 2 weeks) after visit 2. The dentist collects questionnaires and
      diaries and a clinical examination is made. The subject is then completed within the scope of
      the study. Adverse events are registered. If further treatment is required, it is made
      outside the study protocol.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Pain days
time frame: 2 months
description: The change in frequency (number) of pain days
measure: Pain intensity
time frame: 2 months
description: Change in average pain intensity by answering the question: "In the past two weeks", on the average, how intense was your pain rated on a 0-10 scale where 0 is "no pain" and 10 "pain as bad as could be" (That is, your usual jaw pain at times you were experiencing pain)".
measure: Pain intensity on maximal opening of the jaw
time frame: 2 months
description: Change of pain intensity at maximal opening of the jaw. The subject will assess their jaw pain on maximal opening on a numeric rating scale 0-10, where 0 is no pain and 10 is worst pain imaginable.
measure: JFLS-20
time frame: 2 months
description: Change in physical function: Jaw functional problems will be evaluated using the 20-item global Jaw Functional Limitation Scale (JFLS-20), with possible mean scores ranging from 0-10, where 0 i no limitation and 10 is severe limitation.
measure: PHQ-9
time frame: 2 months
description: Change in emotional function using the Patient Health Questionnaire-9 (PHQ-9), a multipurpose instrument used for screening, diagnosing and measuring depression severity, with possible scores ranging from 0-27, where higher scores indicate more severity.
measure: PGIC
time frame: 2 months
description: Global improvement. At the follow-up visit the subjects will rate the change in their overall status since beginning the study treatment using the Patient Global Impression of Change (PGIC) scale, a 7-point scaled instrument ranging from "very much improved" to "very much worse"
measure: GCPS
time frame: 2 months
description: Change in the Graded Chronic Pain Scale, GCPS, pain and its consequences. GCPS assesses 2 dimensions of overall chronic pain severity: pain intensity and pain-related disability. For pain intensity a numeric rating scale 0-10 is used, where 0 is no pain and 10 is worst pain imaginable. For pain-related disability a numeric rating scale from 0-10 is used where 0 is 'no interference' and 10 is 'extreme change'.
arm group label: Botulinum toxin
arm group type: Active Comparator
description: Botulinum toxin type A
arm group label: Saline solution
arm group type: Placebo Comparator
description: NaCl
intervention type: Drug
intervention name: Botulinum toxin type A
description: Intramuscular injection with Botulinum toxin type A in m.masseter and m.temporalis.
arm group label: Botulinum toxin
other name: Botox
intervention type: Other
intervention name: saline solution
description: Intramuscular injection with NaCl in m.masseter and m.temporalis.
arm group label: Saline solution
other name: Physiologic NaCl
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Göran Isacsson, Assoc. Prof.
role: Study Director
affiliation: Stockholm
last name: Mohamad Schumann, DDS
role: Study Director
affiliation: Västerås
last name: Daniel Ovesson, DDS
role: Study Director
affiliation: Karlstad
last name: Ava Minston, DDS
phone: +46196024070
email: ava.minston@regionorebrolan.se
responsible party type: Sponsor
mesh term: Myofascial Pain Syndromes
mesh term: Myalgia
mesh term: Botulinum Toxins
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA
sharing ipd: No