<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/NCT03841227</url>
  </required_header>
  <id_info>
    <org_study_id>2018-0353</org_study_id>
    <nct_id>NCT03841227</nct_id>
  </id_info>
  <brief_title>Effect of tDCS in Intrinsic Functional Brain Connectivity Assessed by Functional Magnetic Resonance in Fibromyalgia</brief_title>
  <official_title>Effect of Transcranial Continuous Current Neuromodulation in Intrinsic Functional Brain Connectivity Assessed by Functional Magnetic Resonance Imaging (fMRI) in Fibromyalgia: A Randomized, Double-blind Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital de Clinicas de Porto Alegre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital de Clinicas de Porto Alegre</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>
      Considering the central component of fibromyalgia (FM), the focus of research on current&#xD;
      therapeutic approaches has been techniques that may modify the dysfunctional neuroplasticity&#xD;
      process, such as transcranial direct current (tDCS) stimulation in order to counteract the&#xD;
      dysfunction responsible for triggering and maintain the symptoms of FM. Although this&#xD;
      technique is gaining space in research and in the clinical scenario, many questions remain to&#xD;
      be answered, such as time of treatment, place to be stimulated and neurophysiological&#xD;
      clarification of the mechanisms involved.&#xD;
&#xD;
      Based on the presented scenario, the present project was organized, being a double-blinded&#xD;
      parallel randomized controlled trial with 20 female patients with FM diagnosed according to&#xD;
      the criteria of the American Society of Rheumatology (2010 - reviewed in 2016) between 19 and&#xD;
      65 years of age, randomized to receive active or simulated anodic pole over the left&#xD;
      dorsolateral prefrontal cortex (DLPFC) (10 patients in each group). Twenty 20-minute&#xD;
      sessions, with a current intensity of 2 milliamperes, will be performed.&#xD;
&#xD;
      In order to respond to the objectives of this study, the IFC will be evaluated before and&#xD;
      after the intervention, through rs-fMRI using seed-based correlation analysis (SCA). The&#xD;
      investigators have a secondary objective to correlate structural connectivity through the&#xD;
      technique of diffusion tensors imaging (DTI) with measures of pain, functional capacity,&#xD;
      depressive symptoms and catastrophism to pain.&#xD;
&#xD;
      The hypothesis is that in FM there is a syndrome of dysfunction in basal intrinsic functional&#xD;
      connectivity (IFC) and that the tDCS has a neuromodulatory effect capable of reducing&#xD;
      connectivity between brain areas related to chronic pain and other neuropsychiatric&#xD;
      components of FM, such as the ventrolateral thalamus, cortex motor, prefrontal cortex,&#xD;
      insular cortex, hippocampus, periaqueductal gray matter, among others. The investigators&#xD;
      believe that a higher cortico-thalamic IFC and between regions with high density of opioid&#xD;
      receptors have a positive predictive response in the treatment of tDCS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Fibromyalgia (FM) is a syndrome that is characterized by generalized musculoskeletal pain,&#xD;
      fatigue, unrepairable sleep, cognitive alterations, depressive and neurovegetative symptoms,&#xD;
      whose neurobiological process is multiple and complex. Although it is of great relevance to&#xD;
      the individual and to society, this pathology often does not receive the necessary attention&#xD;
      by the organs that define the priorities of health care. Population prevalence, according to&#xD;
      the criteria of the American Society of Rheumatology, reaches 5.4%, and the costs of care,&#xD;
      taxes and early retirement due to disability are estimated at more than the US $ 29 billion&#xD;
      per year in the United States. It is known that conventional pharmacological therapies&#xD;
      produce insignificant responses in more than 50% of patients. It is postulated that these&#xD;
      high rates of failure are due in part to a lack of knowledge about pathophysiological&#xD;
      mechanisms. What is known so far is that the peripheral mechanisms contribute to the FM&#xD;
      picture, but dysfunction in central neurobiological pathways surely commands the process,&#xD;
      perpetuating the dysfunctional process that includes central sensitization (CS). CS comprises&#xD;
      the symptoms of fibromyalgia syndrome that culminates in a state of hypersensitivity that&#xD;
      expresses the imbalance of the excitation/inhibition processes that sustain this condition of&#xD;
      non-pathological pain. Functional alterations of the motor cortex and its connections with&#xD;
      subcortical structures that constitute the neuromatrix of pain have now been demonstrated.&#xD;
      Functional magnetic resonance imaging (fMRI), using the resting-state fMRI (rs-fMRI)&#xD;
      technique, has also demonstrated that high intrinsic functional connectivity (IFC) is related&#xD;
      to pain intensity on FM.&#xD;
&#xD;
      Considering the central component of FM, the focus of research on current therapeutic&#xD;
      approaches has been techniques that may modify the dysfunctional neuroplasticity process,&#xD;
      such as transcranial direct current (tDCS) stimulation in order to counteract the dysfunction&#xD;
      responsible for triggering and maintain the symptoms of FM. Although this technique is&#xD;
      gaining space in research and in the clinical scenario, many questions remain to be answered,&#xD;
      such as time of treatment, place to be stimulated and neurophysiological clarification of the&#xD;
      mechanisms involved.&#xD;
&#xD;
      Based on the presented scenario, the present project was organized, being a double-blinded&#xD;
      parallel randomized controlled trial with 20 female patients with FM diagnosed according to&#xD;
      the criteria of the American Society of Rheumatology (2010 - reviewed in 2016) between 19 and&#xD;
      65 years of age, randomized to receive active or simulated anodic pole over the left&#xD;
      dorsolateral prefrontal cortex (DLPFC) (10 patients in each group). Twenty 20 minute&#xD;
      sessions, with a current intensity of 2 milliampere, will be performed.&#xD;
&#xD;
      In order to respond to the objectives of this study, the IFC will be evaluated before and&#xD;
      after the intervention, through rs-fMRI using seed-based correlation analysis (SCA). The&#xD;
      investigators have a secondary objective to correlate structural connectivity through the&#xD;
      technique of diffusion tensors imaging (DTI) with measures of pain, functional capacity,&#xD;
      depressive symptoms and catastrophism to pain.&#xD;
&#xD;
      The hypothesis is that in FM there is a syndrome of dysfunction in basal IFC and that the&#xD;
      tDCS has a neuromodulatory effect capable of reducing connectivity between brain areas&#xD;
      related to chronic pain and other neuropsychiatric components of FM, such as the&#xD;
      ventrolateral thalamus, cortex motor, prefrontal cortex, insular cortex, hippocampus,&#xD;
      periaqueductal gray matter, among others. The investigators believe that a higher&#xD;
      cortico-thalamic IFC and between regions with high density of opioid receptors have a&#xD;
      positive predictive response in the treatment of tDCS.&#xD;
&#xD;
      If the hypothesis is proven, the IFC data may serve as a biological marker associated with&#xD;
      the perception of pain and its clinical presentation, and consequently, open the possibility&#xD;
      of including IFC as a diagnostic parameter and therapeutic response. In addition to the&#xD;
      possible contribution to knowledge production, this project aims to transfer the technology&#xD;
      acquired and developed to the community, and thus benefit millions of people suffering from&#xD;
      chronic FM pain with limited diagnostic and therapeutic perspectives, as well as extending&#xD;
      the knowledge acquired for other neuropsychiatric disorders, such as depression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 1, 2018</start_date>
  <completion_date type="Anticipated">March 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2019</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline Functional cerebral connectivity(rs-fMRI)to post-intervention rs-fMRI</measure>
    <time_frame>30 minutes</time_frame>
    <description>Evaluation of functional cerebral connectivity using resting-state functional magnetic resonance imaging (rs-fMRI) between the change in baseline and post-intervention assessments.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Structural cerebral connectivity</measure>
    <time_frame>30 minutes</time_frame>
    <description>Evaluation of structural cerebral connectivity using diffusion tract imaging (DTI)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Fibromyalgia</condition>
  <arm_group>
    <arm_group_label>Active-tDCS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>10 patients will receive Active-tDCS intervention (2mA, 20 min) at home.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham-tDCS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>10 patients will receive Sham-tDCS intervention (2mA, 20 min) at home.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active-tDCS</intervention_name>
    <description>Active home-based tDCS applied at home. 5 days a week for 4 weeks.</description>
    <arm_group_label>Active-tDCS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham-tDCS</intervention_name>
    <description>Sham home-based tDCS applied at home. 5 days a week for 4 weeks.</description>
    <arm_group_label>Sham-tDCS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Literate&#xD;
&#xD;
          -  Female, between 18 and 65 years old&#xD;
&#xD;
          -  With the diagnosis of fibromyalgia according to the criteria of the American College&#xD;
             of Rheumatology (2010-2016)&#xD;
&#xD;
          -  Pain score equal to or greater than six on the Numerical Pain Scale (NPS 0-10) on most&#xD;
             days of the last 3 months.&#xD;
&#xD;
          -  Give informed consent to participate after the initial evaluation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Living outside the city of Porto Alegre, RS, Brazil&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Severe Mental Illness&#xD;
&#xD;
          -  tDCS contraindications&#xD;
&#xD;
          -  Magnetic resonance imaging (MRI) contraindications&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wolnei Caumo, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Federal University of Rio Grande do Sul</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wolnei Caumo, PhD</last_name>
    <phone>+5551 3359 8083</phone>
    <email>wcaumo@cpovo.net</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hospital de Clinicas de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>90.450-120</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wolnei Caumo, PhD</last_name>
      <phone>+5551 3359 8083</phone>
      <email>wcaumo@hcpa.edu.br</email>
    </contact>
    <investigator>
      <last_name>Wolnei Caumo, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Matheus D Soldatelli, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital de Clinicas e Porto Alegre (HCPA)</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>90035-003</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wolnei Caumo</last_name>
      <phone>55 51 99813977</phone>
      <email>caumo@cpovo.net</email>
    </contact>
    <investigator>
      <last_name>Wolnei Caumo</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>August 4, 2018</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>February 12, 2019</last_update_submitted>
  <last_update_submitted_qc>February 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital de Clinicas de Porto Alegre</investigator_affiliation>
    <investigator_full_name>Wolnei Caumo</investigator_full_name>
    <investigator_title>Professor at the Post-Graduation Program in Medical Sciences, Faculty of Medicine, UFRGS</investigator_title>
  </responsible_party>
  <keyword>fibromyalgia</keyword>
  <keyword>tDCS</keyword>
  <keyword>fMRI</keyword>
  <keyword>rs-fMRI</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>
  <!-- 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/NCT03841227
org study id: 2018-0353
nct id: NCT03841227
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Considering the central component of fibromyalgia (FM), the focus of research on current
      therapeutic approaches has been techniques that may modify the dysfunctional neuroplasticity
      process, such as transcranial direct current (tDCS) stimulation in order to counteract the
      dysfunction responsible for triggering and maintain the symptoms of FM. Although this
      technique is gaining space in research and in the clinical scenario, many questions remain to
      be answered, such as time of treatment, place to be stimulated and neurophysiological
      clarification of the mechanisms involved.

      Based on the presented scenario, the present project was organized, being a double-blinded
      parallel randomized controlled trial with 20 female patients with FM diagnosed according to
      the criteria of the American Society of Rheumatology (2010 - reviewed in 2016) between 19 and
      65 years of age, randomized to receive active or simulated anodic pole over the left
      dorsolateral prefrontal cortex (DLPFC) (10 patients in each group). Twenty 20-minute
      sessions, with a current intensity of 2 milliamperes, will be performed.

      In order to respond to the objectives of this study, the IFC will be evaluated before and
      after the intervention, through rs-fMRI using seed-based correlation analysis (SCA). The
      investigators have a secondary objective to correlate structural connectivity through the
      technique of diffusion tensors imaging (DTI) with measures of pain, functional capacity,
      depressive symptoms and catastrophism to pain.

      The hypothesis is that in FM there is a syndrome of dysfunction in basal intrinsic functional
      connectivity (IFC) and that the tDCS has a neuromodulatory effect capable of reducing
      connectivity between brain areas related to chronic pain and other neuropsychiatric
      components of FM, such as the ventrolateral thalamus, cortex motor, prefrontal cortex,
      insular cortex, hippocampus, periaqueductal gray matter, among others. The investigators
      believe that a higher cortico-thalamic IFC and between regions with high density of opioid
      receptors have a positive predictive response in the treatment of tDCS.
Fibromyalgia (FM) is a syndrome that is characterized by generalized musculoskeletal pain,
      fatigue, unrepairable sleep, cognitive alterations, depressive and neurovegetative symptoms,
      whose neurobiological process is multiple and complex. Although it is of great relevance to
      the individual and to society, this pathology often does not receive the necessary attention
      by the organs that define the priorities of health care. Population prevalence, according to
      the criteria of the American Society of Rheumatology, reaches 5.4%, and the costs of care,
      taxes and early retirement due to disability are estimated at more than the US $ 29 billion
      per year in the United States. It is known that conventional pharmacological therapies
      produce insignificant responses in more than 50% of patients. It is postulated that these
      high rates of failure are due in part to a lack of knowledge about pathophysiological
      mechanisms. What is known so far is that the peripheral mechanisms contribute to the FM
      picture, but dysfunction in central neurobiological pathways surely commands the process,
      perpetuating the dysfunctional process that includes central sensitization (CS). CS comprises
      the symptoms of fibromyalgia syndrome that culminates in a state of hypersensitivity that
      expresses the imbalance of the excitation/inhibition processes that sustain this condition of
      non-pathological pain. Functional alterations of the motor cortex and its connections with
      subcortical structures that constitute the neuromatrix of pain have now been demonstrated.
      Functional magnetic resonance imaging (fMRI), using the resting-state fMRI (rs-fMRI)
      technique, has also demonstrated that high intrinsic functional connectivity (IFC) is related
      to pain intensity on FM.

      Considering the central component of FM, the focus of research on current therapeutic
      approaches has been techniques that may modify the dysfunctional neuroplasticity process,
      such as transcranial direct current (tDCS) stimulation in order to counteract the dysfunction
      responsible for triggering and maintain the symptoms of FM. Although this technique is
      gaining space in research and in the clinical scenario, many questions remain to be answered,
      such as time of treatment, place to be stimulated and neurophysiological clarification of the
      mechanisms involved.

      Based on the presented scenario, the present project was organized, being a double-blinded
      parallel randomized controlled trial with 20 female patients with FM diagnosed according to
      the criteria of the American Society of Rheumatology (2010 - reviewed in 2016) between 19 and
      65 years of age, randomized to receive active or simulated anodic pole over the left
      dorsolateral prefrontal cortex (DLPFC) (10 patients in each group). Twenty 20 minute
      sessions, with a current intensity of 2 milliampere, will be performed.

      In order to respond to the objectives of this study, the IFC will be evaluated before and
      after the intervention, through rs-fMRI using seed-based correlation analysis (SCA). The
      investigators have a secondary objective to correlate structural connectivity through the
      technique of diffusion tensors imaging (DTI) with measures of pain, functional capacity,
      depressive symptoms and catastrophism to pain.

      The hypothesis is that in FM there is a syndrome of dysfunction in basal IFC and that the
      tDCS has a neuromodulatory effect capable of reducing connectivity between brain areas
      related to chronic pain and other neuropsychiatric components of FM, such as the
      ventrolateral thalamus, cortex motor, prefrontal cortex, insular cortex, hippocampus,
      periaqueductal gray matter, among others. The investigators believe that a higher
      cortico-thalamic IFC and between regions with high density of opioid receptors have a
      positive predictive response in the treatment of tDCS.

      If the hypothesis is proven, the IFC data may serve as a biological marker associated with
      the perception of pain and its clinical presentation, and consequently, open the possibility
      of including IFC as a diagnostic parameter and therapeutic response. In addition to the
      possible contribution to knowledge production, this project aims to transfer the technology
      acquired and developed to the community, and thus benefit millions of people suffering from
      chronic FM pain with limited diagnostic and therapeutic perspectives, as well as extending
      the knowledge acquired for other neuropsychiatric disorders, such as depression.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change from Baseline Functional cerebral connectivity(rs-fMRI)to post-intervention rs-fMRI
time frame: 30 minutes
description: Evaluation of functional cerebral connectivity using resting-state functional magnetic resonance imaging (rs-fMRI) between the change in baseline and post-intervention assessments.
measure: Structural cerebral connectivity
time frame: 30 minutes
description: Evaluation of structural cerebral connectivity using diffusion tract imaging (DTI)
arm group label: Active-tDCS
arm group type: Active Comparator
description: 10 patients will receive Active-tDCS intervention (2mA, 20 min) at home.
arm group label: Sham-tDCS
arm group type: Sham Comparator
description: 10 patients will receive Sham-tDCS intervention (2mA, 20 min) at home.
intervention type: Device
intervention name: Active-tDCS
description: Active home-based tDCS applied at home. 5 days a week for 4 weeks.
arm group label: Active-tDCS
intervention type: Device
intervention name: Sham-tDCS
description: Sham home-based tDCS applied at home. 5 days a week for 4 weeks.
arm group label: Sham-tDCS
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Wolnei Caumo, PhD
role: Principal Investigator
affiliation: Federal University of Rio Grande do Sul
last name: Wolnei Caumo, PhD
phone: +5551 3359 8083
email: wcaumo@cpovo.net
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Hospital de Clinicas de Porto Alegre
investigator full name: Wolnei Caumo
investigator title: Professor at the Post-Graduation Program in Medical Sciences, Faculty of Medicine, UFRGS
mesh term: Fibromyalgia
mesh term: Myofascial Pain Syndromes