xml: <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/NCT06006130</url>
    </required_header>
    <id_info>
      <org_study_id>16482</org_study_id>
      <nct_id>NCT06006130</nct_id>
    </id_info>
    <brief_title>Neurophysiology of Fibromyalgia</brief_title>
    <official_title>Investigating the Neurobiological Contributions to Pain in Patients With Fibromyalgia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>McMaster University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>McMaster University</source>
    <oversight_info>
      <has_dmc>No</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>
        Fibromyalgia is a syndrome associated with fatigue and chronic pain, leading to significant&#xD;
        physical limitations and impaired quality of life. There are several challenges that&#xD;
        complicate the diagnosis and management of fibromyalgia. The etiology is not well defined, as&#xD;
        there are several proposed factors that may trigger the genesis of pain in fibromyalgia&#xD;
        including physical and/or emotional life stressors, and genetic predispositions involving&#xD;
        neuromodulator pathways. Chronic pain in fibromyalgia arises in the absence of tissue&#xD;
        pathology, and consequently a lack of consensus on reliable diagnostic criteria.&#xD;
        Understanding the neurophysiology of fibromyalgia would aid in the discovery of objective&#xD;
        biomarkers for diagnosis. Therefore, the goals of this study are to:&#xD;
  &#xD;
          1. Compare the neurophysiological responses in fibromyalgia compared to healthy controls.&#xD;
  &#xD;
          2. Determine whether a two-week rTMS protocol will alter pain in individuals with&#xD;
             fibromyalgia.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Fibromyalgia is a syndrome associated with fatigue and chronic pain, leading to significant&#xD;
        physical limitations and impaired quality of life. Fibromyalgia affects 1.7% of Canadians,&#xD;
        with a higher prevalence in females compared to males at 9:1 [1]. There are several&#xD;
        challenges that complicate the diagnosis and management of fibromyalgia. The etiology is not&#xD;
        well defined, as there are several proposed factors that may trigger the genesis of pain in&#xD;
        fibromyalgia. Chronic pain in fibromyalgia arises in the absence of tissue pathology, and&#xD;
        consequently a lack of consensus on reliable diagnostic criteria. Understanding the&#xD;
        pathophysiology of fibromyalgia would aid in the identification of objective biomarkers that&#xD;
        could be used for diagnosis.&#xD;
  &#xD;
        Multiple theories have been posited to explain the genesis of chronic pain. The gate control&#xD;
        theory describes the attenuation of pain signals in the spinal cord prior to cortical&#xD;
        processing, and it has been hypothesized that loss of this gate control leads to the genesis&#xD;
        of chronic pain [2]. Gate control can be observed by reduction of afferent signals during&#xD;
        active muscle contraction. For example, the amplitude of the somatosensory-evoked potential&#xD;
        (SEP) is attenuated during active contraction [3]. To our knowledge, it is unknown whether&#xD;
        such gate control is observed in fibromyalgia. The lack of gate control may contribute to&#xD;
        chronic pain in this population.&#xD;
  &#xD;
        The sensorimotor theory suggests that incongruency between motor intention and sensory&#xD;
        feedback underlies chronic pain where there is an absence of tissue pathology [4]. This may&#xD;
        align with the genesis of fibromyalgia, given the findings that those with fibromyalgia have&#xD;
        altered tactile and proprioceptive functioning [5]. Corticomuscular coherence (CMC) is a&#xD;
        useful tool that uses electroencephalography (EEG) and electromyography (EMG) to probe the&#xD;
        synchrony of neural firing between the brain and muscle [6]. To our knowledge, it is unknown&#xD;
        how the magnitude of CMC varies in fibromyalgia compared to healthy controls.&#xD;
  &#xD;
        Non-invasive brain stimulation in the form of Transcranial Magnetic Stimulation (TMS) has&#xD;
        been used to probe the activity of corticospinal and cortical networks in fibromyalgia. When&#xD;
        TMS pulses are delivered in a repetitive train, a protocol known as repetitive TMS (rTMS),&#xD;
        short-term neuroplasticity can be induced (i.e., a change in the activity of neurons in the&#xD;
        brain). In fibromyalgia, Mhalla et al. [7] found that 5 days of 10 Hz rTMS reduced pain&#xD;
        intensity and improved quality of life metrics. It is unknown whether a longer intervention&#xD;
        period could lead to greater analgesic effects.&#xD;
  &#xD;
        Finally, central sensitization may explain the widespread chronic pain experienced in&#xD;
        fibromyalgia. There are several neuromodulators that contribute to the neurobiology of&#xD;
        central sensitization and may be implicated in this condition including serotonin, dopamine,&#xD;
        and brain-derived neurotrophic factor (BDNF). Serotonin is linked to pain modulation, such&#xD;
        that increased levels of 5-HT are associated with hyperalgesia [8]. BDNF has been implicated&#xD;
        in the genesis of neuropathic pain [9]. In fibromyalgia compared to healthy controls, serum&#xD;
        BDNF levels have been reported to be higher [10]. Abnormal dopamine function may also be&#xD;
        associated with fibromyalgia [11]. Positron-emission tomography (PET) studies show lower&#xD;
        cortical dopamine D2/D3 binding availability in fibromyalgia compared to healthy controls&#xD;
        [12].&#xD;
  &#xD;
        Ultimately, a combination of events may lead to widespread chronic pain in fibromyalgia.&#xD;
        Understanding the neurophysiology of fibromyalgia would aid in the discovery of objective&#xD;
        biomarkers for diagnosis. Therefore, the goals of this study are to:&#xD;
  &#xD;
        1. Compare the neurophysiological responses in fibromyalgia compared to healthy controls.&#xD;
  &#xD;
        2. Determine whether a two-week rTMS protocol will alter pain in individuals with&#xD;
        fibromyalgia.&#xD;
  &#xD;
          1. M. B. Yunus, &quot;The role of gender in fibromyalgia syndrome,&quot; Curr Rheumatol Rep, vol. 3,&#xD;
             no. 2, pp. 128-134, 2001, doi: 10.1007/S11926-001-0008-3.&#xD;
  &#xD;
          2. R. Melzack, &quot;Evolution of the neuromatrix theory of pain. The Prithvi Raj Lecture:&#xD;
             presented at the third World Congress of World Institute of Pain, Barcelona 2004,&quot; Pain&#xD;
             Pract, vol. 5, no. 2, pp. 85-94, Jun. 2005, doi: 10.1111/J.1533-2500.2005.05203.X.&#xD;
  &#xD;
          3. H. Nakata, K. Inui, T. Wasaka, Y. Nishihira, and R. Kakigi, &quot;Mechanisms of differences&#xD;
             in gating effects on short-and long-latency somatosensory evoked potentials relating to&#xD;
             movement,&quot; Brain Topogr, vol. 15, no. 4, pp. 211-222, Jun. 2003, doi:&#xD;
             10.1023/A:1023908707851.&#xD;
  &#xD;
          4. A. D. Vittersø, M. Halicka, G. Buckingham, M. J. Proulx, and J. H. Bultitude, &quot;The&#xD;
             sensorimotor theory of pathological pain revisited,&quot; Neurosci Biobehav Rev, vol. 139,&#xD;
             Aug. 2022, doi: 10.1016/J.NEUBIOREV.2022.104735.&#xD;
  &#xD;
          5. S. Toprak Celenay, O. Mete, O. Coban, D. Oskay, and S. Erten, &quot;Trunk position sense,&#xD;
             postural stability, and spine posture in fibromyalgia,&quot; Rheumatol Int, vol. 39, no. 12,&#xD;
             pp. 2087-2094, Dec. 2019, doi: 10.1007/S00296-019-04399-1/TABLES/2.&#xD;
  &#xD;
          6. A. Chowdhury, H. Raza, Y. K. Meena, A. Dutta, and G. Prasad, &quot;An EEG-EMG&#xD;
             correlation-based brain-computer interface for hand orthosis supported&#xD;
             neuro-rehabilitation,&quot; J Neurosci Methods, vol. 312, pp. 1-11, Jan. 2019, doi:&#xD;
             10.1016/J.JNEUMETH.2018.11.010.&#xD;
  &#xD;
          7. A. Mhalla et al., &quot;Long-term maintenance of the analgesic effects of transcranial&#xD;
             magnetic stimulation in fibromyalgia,&quot; Pain, vol. 152, no. 7, pp. 1478-1485, 2011, doi:&#xD;
             10.1016/J.PAIN.2011.01.034.&#xD;
  &#xD;
          8. E. A. Ovrom, K. A. ; Mostert, S. ; Khakhkhar, D. P. ; Mckee, P. ; Yang, and Y. F. A.&#xD;
             Her, &quot;A Comprehensive Review of the Genetic and Epigenetic Contributions to the&#xD;
             Development of Fibromyalgia,&quot; Biomedicines 2023, Vol. 11, Page 1119, vol. 11, no. 4, p.&#xD;
             1119, Apr. 2023, doi: 10.3390/BIOMEDICINES11041119.&#xD;
  &#xD;
          9. K. Obata and K. Noguchi, &quot;BDNF in sensory neurons and chronic pain,&quot; Neurosci Res, vol.&#xD;
             55, no. 1, pp. 1-10, May 2006, doi: 10.1016/J.NEURES.2006.01.005.&#xD;
  &#xD;
         10. A. Deitos et al., &quot;Clinical Value of Serum Neuroplasticity Mediators in Identifying the&#xD;
             Central Sensitivity Syndrome in Patients With Chronic Pain With and Without Structural&#xD;
             Pathology,&quot; Clin J Pain, vol. 31, no. 11, pp. 959-967, 2015, doi:&#xD;
             10.1097/AJP.0000000000000194.&#xD;
  &#xD;
         11. P. B. Wood, M. F. Glabus, R. Simpson, and J. C. Patterson, &quot;Changes in gray matter&#xD;
             density in fibromyalgia: correlation with dopamine metabolism,&quot; J Pain, vol. 10, no. 6,&#xD;
             pp. 609-618, Jun. 2009, doi: 10.1016/J.JPAIN.2008.12.008.&#xD;
  &#xD;
         12. D. S. Albrecht et al., &quot;Differential dopamine function in fibromyalgia,&quot; Brain Imaging&#xD;
             Behav, vol. 10, no. 3, pp. 829-839, Sep. 2016, doi: 10.1007/S11682-015-9459-4/FIGURES/4.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">May 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">May 30, 2025</primary_completion_date>
    <phase>N/A</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>
      <intervention_model_description>Experiment 1: Response to real intervention compared between fibromyalgia and healthy control group Experiment 2: Fibromyalgia participants allocated to real or sham intervention</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Outcomes Assessor)</masking>
      <masking_description>Experiment 1: Outcomes assessor will be blinded to the groups (fibromyalgia vs controls) the data is obtained from Experiment 2: Outcomes assessor and participants will be blinded to the intervention group that participants are allocated to (sham vs real treatment)</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Change in PROMIS-29 v2.0 Profile</measure>
      <time_frame>Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention</time_frame>
      <description>Using numerical rating (0 to 5) to assess the change in seven health domains including physical function, anxiety, depression, fatigue, sleep disturbances, ability to participate in social roles and activities, and pain interference. Each category consists of 4 questions. Also uses a numerical rating to asses pain intensity (0-10).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Fibromyalgia impact questionnaire (FIQ)</measure>
      <time_frame>Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention</time_frame>
      <description>This instrument will be used to assess the patients feeling and emotion related to their pain experience.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in Pain catastrophizing scale-EN-SF</measure>
      <time_frame>Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention</time_frame>
      <description>Will be used to assess the patients feeling and emotion related to their pain experience</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Patient Health Questionnaire-4 (PHQ-4)</measure>
      <time_frame>Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention</time_frame>
      <description>Will be used to assess for symptoms of for Major Depressive Disorder and Generalized Anxiety Disorder</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Short-form Posttraumatic Checklist-5 (Short-form PCL-5)</measure>
      <time_frame>Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention</time_frame>
      <description>Will be used to screen for symptoms of Posttraumatic Stress Disorder (PTSD)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Motor-evoked potentials (MEPs)</measure>
      <time_frame>Experiment 1: At baseline pre-intervention and immediately following 1 treatment session, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention</time_frame>
      <description>This will include an assessments of MEPs obtained using Transcranial Magnetic Stimulation (TMS).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Short-Interval Intracortical Inhibition (SICI)</measure>
      <time_frame>Experiment 1: At baseline pre-intervention and immediately following 1 treatment session, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention</time_frame>
      <description>This will include an assessments of SICI obtained using Transcranial Magnetic Stimulation (TMS).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in performance on sensorimotor tasks</measure>
      <time_frame>Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention</time_frame>
      <description>Tasks include tactile localization, temporal order judgement (TOJ), and sequential amplitude discrimination</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EEG assessment of Somatosensory-evoked potentials (SEPs)</measure>
      <time_frame>Experiment 1: At baseline pre-intervention only</time_frame>
      <description>This will include an assessment of SEPs using EEG electrodes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EEG assessment of Pain-related evoked potentials (PREPs)</measure>
      <time_frame>Experiment 1: At baseline pre-intervention only</time_frame>
      <description>This will include an assessment of PREPs using EEG electrodes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EEG assessment of Corticomuscular coherence (CMC)</measure>
      <time_frame>Experiment 1: At baseline pre-intervention only</time_frame>
      <description>This will include an assessment of CMC using EEG electrodes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EEG assessment of Event-related desynchronization (ERD)</measure>
      <time_frame>Experiment 1: At baseline pre-intervention only</time_frame>
      <description>This will include an assessment of ERD using EEG electrodes.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Fibromyalgia</condition>
    <arm_group>
      <arm_group_label>Active rTMS</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Repetitive Transcranial Magnetic Stimulation (rTMS) will be delivered at 10 Hz, 1500 pulses targeting the hand representation of the left primary motor cortex. rTMS delivery will require ~11 min to complete. In Experiment 1, this intervention will be performed for 1 session (~11min). In Experiment 2, this intervention will be performed approximately 5 days per week for 2 weeks. In addition, participants will experience their standard medical care.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham rTMS</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>Sham rTMS will be delivered at as a placebo control. It is important to note that from the participant perspective, the sham stimulation will feel and sound identical to active rTMS. In Experiment 2, this intervention will be performed approximately 5 days per week for 2 weeks. In addition, participants will experience their standard medical care.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Active Repetitive Transcranial Magnetic Stimulation (rTMS)</intervention_name>
      <description>rTMS is a non-invasive, non-painful procedure used to relieve chronic pain and promote short-term changes. The abductor pollicis brevis (APB) muscle of the left motor cortex will be targeted using neuronavigation software. 1500 pulses will be delivered at 10 Hz stimulation. Stimulation will be delivered at 80% of the resting motor threshold obtained from the right APB muscle. The delivery of rTMS requires 11 minutes in total.</description>
      <arm_group_label>Active rTMS</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Sham Repetitive Transcranial Magnetic Stimulation (rTMS)</intervention_name>
      <description>A sham coil will be utilized for the sham rTMS condition. It is important to note that from the participant perspective, the sham stimulation will feel and sound identical to active. The location and all other parameters of Sham rTMS will be identical to Active rTMS.</description>
      <arm_group_label>Sham rTMS</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  18-65 years old&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  contraindications to TMS&#xD;
  &#xD;
            -  chronic pain associated with diagnoses other than fibromyalgia&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>20 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>McMaster University</name>
        <address>
          <city>Hamilton</city>
          <state>Ontario</state>
          <zip>L8S4L1</zip>
          <country>Canada</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>McMaster University</investigator_affiliation>
      <investigator_full_name>Aimee Nelson</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>fibromyalgia</keyword>
    <keyword>transcranial magnetic stimulation</keyword>
    <keyword>neuroplasticity</keyword>
    <keyword>pain</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Fibromyalgia</mesh_term>
      <mesh_term>Myofascial Pain Syndromes</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06006130
  org study id: 16482
  nct id: NCT06006130
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Fibromyalgia is a syndrome associated with fatigue and chronic pain, leading to significant
        physical limitations and impaired quality of life. There are several challenges that
        complicate the diagnosis and management of fibromyalgia. The etiology is not well defined, as
        there are several proposed factors that may trigger the genesis of pain in fibromyalgia
        including physical and/or emotional life stressors, and genetic predispositions involving
        neuromodulator pathways. Chronic pain in fibromyalgia arises in the absence of tissue
        pathology, and consequently a lack of consensus on reliable diagnostic criteria.
        Understanding the neurophysiology of fibromyalgia would aid in the discovery of objective
        biomarkers for diagnosis. Therefore, the goals of this study are to:
  
          1. Compare the neurophysiological responses in fibromyalgia compared to healthy controls.
  
          2. Determine whether a two-week rTMS protocol will alter pain in individuals with
             fibromyalgia.
  Fibromyalgia is a syndrome associated with fatigue and chronic pain, leading to significant
        physical limitations and impaired quality of life. Fibromyalgia affects 1.7% of Canadians,
        with a higher prevalence in females compared to males at 9:1 [1]. There are several
        challenges that complicate the diagnosis and management of fibromyalgia. The etiology is not
        well defined, as there are several proposed factors that may trigger the genesis of pain in
        fibromyalgia. Chronic pain in fibromyalgia arises in the absence of tissue pathology, and
        consequently a lack of consensus on reliable diagnostic criteria. Understanding the
        pathophysiology of fibromyalgia would aid in the identification of objective biomarkers that
        could be used for diagnosis.
  
        Multiple theories have been posited to explain the genesis of chronic pain. The gate control
        theory describes the attenuation of pain signals in the spinal cord prior to cortical
        processing, and it has been hypothesized that loss of this gate control leads to the genesis
        of chronic pain [2]. Gate control can be observed by reduction of afferent signals during
        active muscle contraction. For example, the amplitude of the somatosensory-evoked potential
        (SEP) is attenuated during active contraction [3]. To our knowledge, it is unknown whether
        such gate control is observed in fibromyalgia. The lack of gate control may contribute to
        chronic pain in this population.
  
        The sensorimotor theory suggests that incongruency between motor intention and sensory
        feedback underlies chronic pain where there is an absence of tissue pathology [4]. This may
        align with the genesis of fibromyalgia, given the findings that those with fibromyalgia have
        altered tactile and proprioceptive functioning [5]. Corticomuscular coherence (CMC) is a
        useful tool that uses electroencephalography (EEG) and electromyography (EMG) to probe the
        synchrony of neural firing between the brain and muscle [6]. To our knowledge, it is unknown
        how the magnitude of CMC varies in fibromyalgia compared to healthy controls.
  
        Non-invasive brain stimulation in the form of Transcranial Magnetic Stimulation (TMS) has
        been used to probe the activity of corticospinal and cortical networks in fibromyalgia. When
        TMS pulses are delivered in a repetitive train, a protocol known as repetitive TMS (rTMS),
        short-term neuroplasticity can be induced (i.e., a change in the activity of neurons in the
        brain). In fibromyalgia, Mhalla et al. [7] found that 5 days of 10 Hz rTMS reduced pain
        intensity and improved quality of life metrics. It is unknown whether a longer intervention
        period could lead to greater analgesic effects.
  
        Finally, central sensitization may explain the widespread chronic pain experienced in
        fibromyalgia. There are several neuromodulators that contribute to the neurobiology of
        central sensitization and may be implicated in this condition including serotonin, dopamine,
        and brain-derived neurotrophic factor (BDNF). Serotonin is linked to pain modulation, such
        that increased levels of 5-HT are associated with hyperalgesia [8]. BDNF has been implicated
        in the genesis of neuropathic pain [9]. In fibromyalgia compared to healthy controls, serum
        BDNF levels have been reported to be higher [10]. Abnormal dopamine function may also be
        associated with fibromyalgia [11]. Positron-emission tomography (PET) studies show lower
        cortical dopamine D2/D3 binding availability in fibromyalgia compared to healthy controls
        [12].
  
        Ultimately, a combination of events may lead to widespread chronic pain in fibromyalgia.
        Understanding the neurophysiology of fibromyalgia would aid in the discovery of objective
        biomarkers for diagnosis. Therefore, the goals of this study are to:
  
        1. Compare the neurophysiological responses in fibromyalgia compared to healthy controls.
  
        2. Determine whether a two-week rTMS protocol will alter pain in individuals with
        fibromyalgia.
  
          1. M. B. Yunus, "The role of gender in fibromyalgia syndrome," Curr Rheumatol Rep, vol. 3,
             no. 2, pp. 128-134, 2001, doi: 10.1007/S11926-001-0008-3.
  
          2. R. Melzack, "Evolution of the neuromatrix theory of pain. The Prithvi Raj Lecture:
             presented at the third World Congress of World Institute of Pain, Barcelona 2004," Pain
             Pract, vol. 5, no. 2, pp. 85-94, Jun. 2005, doi: 10.1111/J.1533-2500.2005.05203.X.
  
          3. H. Nakata, K. Inui, T. Wasaka, Y. Nishihira, and R. Kakigi, "Mechanisms of differences
             in gating effects on short-and long-latency somatosensory evoked potentials relating to
             movement," Brain Topogr, vol. 15, no. 4, pp. 211-222, Jun. 2003, doi:
             10.1023/A:1023908707851.
  
          4. A. D. Vittersø, M. Halicka, G. Buckingham, M. J. Proulx, and J. H. Bultitude, "The
             sensorimotor theory of pathological pain revisited," Neurosci Biobehav Rev, vol. 139,
             Aug. 2022, doi: 10.1016/J.NEUBIOREV.2022.104735.
  
          5. S. Toprak Celenay, O. Mete, O. Coban, D. Oskay, and S. Erten, "Trunk position sense,
             postural stability, and spine posture in fibromyalgia," Rheumatol Int, vol. 39, no. 12,
             pp. 2087-2094, Dec. 2019, doi: 10.1007/S00296-019-04399-1/TABLES/2.
  
          6. A. Chowdhury, H. Raza, Y. K. Meena, A. Dutta, and G. Prasad, "An EEG-EMG
             correlation-based brain-computer interface for hand orthosis supported
             neuro-rehabilitation," J Neurosci Methods, vol. 312, pp. 1-11, Jan. 2019, doi:
             10.1016/J.JNEUMETH.2018.11.010.
  
          7. A. Mhalla et al., "Long-term maintenance of the analgesic effects of transcranial
             magnetic stimulation in fibromyalgia," Pain, vol. 152, no. 7, pp. 1478-1485, 2011, doi:
             10.1016/J.PAIN.2011.01.034.
  
          8. E. A. Ovrom, K. A. ; Mostert, S. ; Khakhkhar, D. P. ; Mckee, P. ; Yang, and Y. F. A.
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  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Experiment 1: Response to real intervention compared between fibromyalgia and healthy control group Experiment 2: Fibromyalgia participants allocated to real or sham intervention
  primary purpose: Treatment
  masking: Double (Participant, Outcomes Assessor)
  masking description: Experiment 1: Outcomes assessor will be blinded to the groups (fibromyalgia vs controls) the data is obtained from Experiment 2: Outcomes assessor and participants will be blinded to the intervention group that participants are allocated to (sham vs real treatment)
  measure: Change in PROMIS-29 v2.0 Profile
  time frame: Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention
  description: Using numerical rating (0 to 5) to assess the change in seven health domains including physical function, anxiety, depression, fatigue, sleep disturbances, ability to participate in social roles and activities, and pain interference. Each category consists of 4 questions. Also uses a numerical rating to asses pain intensity (0-10).
  measure: Change in Fibromyalgia impact questionnaire (FIQ)
  time frame: Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention
  description: This instrument will be used to assess the patients feeling and emotion related to their pain experience.
  measure: Change in Pain catastrophizing scale-EN-SF
  time frame: Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention
  description: Will be used to assess the patients feeling and emotion related to their pain experience
  measure: Change in Patient Health Questionnaire-4 (PHQ-4)
  time frame: Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention
  description: Will be used to assess for symptoms of for Major Depressive Disorder and Generalized Anxiety Disorder
  measure: Change in Short-form Posttraumatic Checklist-5 (Short-form PCL-5)
  time frame: Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention
  description: Will be used to screen for symptoms of Posttraumatic Stress Disorder (PTSD)
  measure: Change in Motor-evoked potentials (MEPs)
  time frame: Experiment 1: At baseline pre-intervention and immediately following 1 treatment session, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention
  description: This will include an assessments of MEPs obtained using Transcranial Magnetic Stimulation (TMS).
  measure: Change in Short-Interval Intracortical Inhibition (SICI)
  time frame: Experiment 1: At baseline pre-intervention and immediately following 1 treatment session, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention
  description: This will include an assessments of SICI obtained using Transcranial Magnetic Stimulation (TMS).
  measure: Change in performance on sensorimotor tasks
  time frame: Experiment 1: At baseline pre-intervention, Experiment 2: At baseline pre-intervention and 2 weeks post-intervention
  description: Tasks include tactile localization, temporal order judgement (TOJ), and sequential amplitude discrimination
  measure: EEG assessment of Somatosensory-evoked potentials (SEPs)
  time frame: Experiment 1: At baseline pre-intervention only
  description: This will include an assessment of SEPs using EEG electrodes.
  measure: EEG assessment of Pain-related evoked potentials (PREPs)
  time frame: Experiment 1: At baseline pre-intervention only
  description: This will include an assessment of PREPs using EEG electrodes.
  measure: EEG assessment of Corticomuscular coherence (CMC)
  time frame: Experiment 1: At baseline pre-intervention only
  description: This will include an assessment of CMC using EEG electrodes.
  measure: EEG assessment of Event-related desynchronization (ERD)
  time frame: Experiment 1: At baseline pre-intervention only
  description: This will include an assessment of ERD using EEG electrodes.
  arm group label: Active rTMS
  arm group type: Active Comparator
  description: Repetitive Transcranial Magnetic Stimulation (rTMS) will be delivered at 10 Hz, 1500 pulses targeting the hand representation of the left primary motor cortex. rTMS delivery will require ~11 min to complete. In Experiment 1, this intervention will be performed for 1 session (~11min). In Experiment 2, this intervention will be performed approximately 5 days per week for 2 weeks. In addition, participants will experience their standard medical care.
  arm group label: Sham rTMS
  arm group type: Sham Comparator
  description: Sham rTMS will be delivered at as a placebo control. It is important to note that from the participant perspective, the sham stimulation will feel and sound identical to active rTMS. In Experiment 2, this intervention will be performed approximately 5 days per week for 2 weeks. In addition, participants will experience their standard medical care.
  intervention type: Device
  intervention name: Active Repetitive Transcranial Magnetic Stimulation (rTMS)
  description: rTMS is a non-invasive, non-painful procedure used to relieve chronic pain and promote short-term changes. The abductor pollicis brevis (APB) muscle of the left motor cortex will be targeted using neuronavigation software. 1500 pulses will be delivered at 10 Hz stimulation. Stimulation will be delivered at 80% of the resting motor threshold obtained from the right APB muscle. The delivery of rTMS requires 11 minutes in total.
  arm group label: Active rTMS
  intervention type: Device
  intervention name: Sham Repetitive Transcranial Magnetic Stimulation (rTMS)
  description: A sham coil will be utilized for the sham rTMS condition. It is important to note that from the participant perspective, the sham stimulation will feel and sound identical to active. The location and all other parameters of Sham rTMS will be identical to Active rTMS.
  arm group label: Sham rTMS
  criteria: 
  gender: All
  minimum age: 20 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  facility: 
  country: Canada
  responsible party type: Principal Investigator
  investigator affiliation: McMaster University
  investigator full name: Aimee Nelson
  investigator title: Professor
  mesh term: Fibromyalgia
  mesh term: Myofascial Pain Syndromes
  sharing ipd: Undecided