<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/NCT02195271</url>
  </required_header>
  <id_info>
    <org_study_id>130155</org_study_id>
    <nct_id>NCT02195271</nct_id>
  </id_info>
  <brief_title>Neuroplasticity:Melatonin and Transcranial Current Stimulation in Healthy Subjects.</brief_title>
  <official_title>Effect of Melatonin and Transcranial Direct Current Stimulation (tDCS) on Neuroplasticity and the Heat-pain Detection Threshold in Healthy Subjects:Randomized, Double-blind,Crossover 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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pain exerts a tremendous cost in healthy care, rehabilitation and lost productivity. It is is&#xD;
      associated with a wide range of diseases and their social consequences is a public health&#xD;
      problem.&#xD;
&#xD;
      With the progress of neuroscience and studies on the plasticity of the central nervous&#xD;
      system, it has been provided a better understanding of the neurobiological mechanisms of&#xD;
      pain.&#xD;
&#xD;
      The neurohormone Melatonin stands by having systemic and diverse mechanisms of action, both&#xD;
      in physiological and pathological situations, with modulating effects on the process of&#xD;
      nociceptive signaling and neurochemical mechanisms such as serotonergic, opioidergic and&#xD;
      GABAergic, exerting anti-inflammatory action, analgesic activity among others.&#xD;
&#xD;
      The advent of neuromodulation techniques such as transcranial direct current stimulation&#xD;
      (tDCS), which promote changes in neuronal activity and signaling to be effective in&#xD;
      conditions of chronic pain by attenuating changes in cortical excitability.&#xD;
&#xD;
      There is clinical evidence of the analgesic effect of Melatonin and tDCS alone. Thus,&#xD;
      considering the potential for each isolated intervention and the lack of knowledge of their&#xD;
      combined effect, the authors propose the present study to investigate the effect of this&#xD;
      combination on the heat-pain detection threshold and the neuroplasticity in the healthy&#xD;
      subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The methods are according to the CONSORT guidelines.&#xD;
&#xD;
      Heat pain threshold and tolerance : Quantitative Sensory Testing (QST) will be used on a&#xD;
      computer Peltier-based device thermode.&#xD;
&#xD;
      Conditioned Pain Modulation (CPM)-task: Immerssing the non-dominant hand cold water for 1&#xD;
      minute.&#xD;
&#xD;
      Serum Brain Derived Neurotrophic Factor (BDNF).&#xD;
&#xD;
      Transcranial Magnetic Stimulation (TMS) assessment: motor threshold, motor evoked potential,&#xD;
      Short intracortical inhibition and intracortical facilitation.&#xD;
&#xD;
      Statistical analyses: Descriptive statistics, Linear and multiple regression analysis,&#xD;
      performed with SPSS version18.0.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>March 2014</start_date>
  <completion_date type="Anticipated">August 2014</completion_date>
  <primary_completion_date type="Anticipated">August 2014</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>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in heat-pain threshold with pain score</measure>
    <time_frame>Baseline, one week</time_frame>
    <description>Heat-threshold by Pettier-based device on the contralateral hand assessment pain score (VAS)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Brain-Derived neurotrophic factor (BDNF)</measure>
    <time_frame>Baseline, one week</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline from Catastrophizing Scale</measure>
    <time_frame>Baseline, one week</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Inventory of state-trait anxiety Scale</measure>
    <time_frame>Baseline, one week</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Inventory of Coping</measure>
    <time_frame>Baseline, one week</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of cortical excitability</measure>
    <time_frame>Baseline, one week</time_frame>
    <description>Transcranial Magnetic Stimulation (TMS) assessment motor threshold, motor-evoked potentials, silent period, intracortical inhibition and facilitation</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Analgesia Disorder</condition>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Melatonin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>0,25mg/Kg sl before tDCS</description>
  </arm_group>
  <arm_group>
    <arm_group_label>tDCS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transcranial direct current stimulation once time. Dose 2 mA, 20 seconds.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial Direct Current Stimulation (tDCS)</intervention_name>
    <arm_group_label>tDCS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melatonin</intervention_name>
    <arm_group_label>Melatonin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male 18-40 years old&#xD;
&#xD;
          -  Healthy&#xD;
&#xD;
          -  Without medication&#xD;
&#xD;
          -  Sign the informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who did not understand the Portuguese&#xD;
&#xD;
          -  Acute or chronic pain conditions&#xD;
&#xD;
          -  Medical or psychiatric disorders&#xD;
&#xD;
          -  History of alcohol or substance abuse&#xD;
&#xD;
          -  Neurological disorder&#xD;
&#xD;
          -  Use of medications affect in the central nervous system&#xD;
&#xD;
          -  Traumatic brain injury&#xD;
&#xD;
          -  Neurosurgery&#xD;
&#xD;
          -  Metallic implant in the brain&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wolnei Caumo</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital de Clinicas de Porto Alegre - UFRGS</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wolnei Caumo, PhD</last_name>
    <phone>555133598083</phone>
    <email>caumo@cpovo.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nadia Jardim, MD</last_name>
    <phone>555133598083</phone>
    <email>nrjs@ufpa.br</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hospital de Clinicas de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <state>RS</state>
        <zip>900035-903</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wolnei Caumo</last_name>
      <phone>555133590083</phone>
      <email>caumo@cpovo.net</email>
    </contact>
    <investigator>
      <last_name>Nadia Jardim, MD, Msc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>March 19, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <last_update_submitted>July 18, 2014</last_update_submitted>
  <last_update_submitted_qc>July 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 21, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Melatonin</keyword>
  <keyword>Transcranial Direct Current Stimulation</keyword>
  <keyword>Neuroplasticity</keyword>
  <keyword>Analgesia</keyword>
  <keyword>Pain</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02195271
org study id: 130155
nct id: NCT02195271
lead sponsor: 
has dmc: Yes
Pain exerts a tremendous cost in healthy care, rehabilitation and lost productivity. It is is
      associated with a wide range of diseases and their social consequences is a public health
      problem.

      With the progress of neuroscience and studies on the plasticity of the central nervous
      system, it has been provided a better understanding of the neurobiological mechanisms of
      pain.

      The neurohormone Melatonin stands by having systemic and diverse mechanisms of action, both
      in physiological and pathological situations, with modulating effects on the process of
      nociceptive signaling and neurochemical mechanisms such as serotonergic, opioidergic and
      GABAergic, exerting anti-inflammatory action, analgesic activity among others.

      The advent of neuromodulation techniques such as transcranial direct current stimulation
      (tDCS), which promote changes in neuronal activity and signaling to be effective in
      conditions of chronic pain by attenuating changes in cortical excitability.

      There is clinical evidence of the analgesic effect of Melatonin and tDCS alone. Thus,
      considering the potential for each isolated intervention and the lack of knowledge of their
      combined effect, the authors propose the present study to investigate the effect of this
      combination on the heat-pain detection threshold and the neuroplasticity in the healthy
      subjects.
The methods are according to the CONSORT guidelines.

      Heat pain threshold and tolerance : Quantitative Sensory Testing (QST) will be used on a
      computer Peltier-based device thermode.

      Conditioned Pain Modulation (CPM)-task: Immerssing the non-dominant hand cold water for 1
      minute.

      Serum Brain Derived Neurotrophic Factor (BDNF).

      Transcranial Magnetic Stimulation (TMS) assessment: motor threshold, motor evoked potential,
      Short intracortical inhibition and intracortical facilitation.

      Statistical analyses: Descriptive statistics, Linear and multiple regression analysis,
      performed with SPSS version18.0.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from baseline in heat-pain threshold with pain score
time frame: Baseline, one week
description: Heat-threshold by Pettier-based device on the contralateral hand assessment pain score (VAS)
measure: Change from baseline Brain-Derived neurotrophic factor (BDNF)
time frame: Baseline, one week
measure: Change from Baseline from Catastrophizing Scale
time frame: Baseline, one week
measure: Change from baseline Inventory of state-trait anxiety Scale
time frame: Baseline, one week
measure: Change from baseline Inventory of Coping
time frame: Baseline, one week
measure: Change from baseline of cortical excitability
time frame: Baseline, one week
description: Transcranial Magnetic Stimulation (TMS) assessment motor threshold, motor-evoked potentials, silent period, intracortical inhibition and facilitation
arm group label: Melatonin
arm group type: Active Comparator
description: 0,25mg/Kg sl before tDCS
arm group label: tDCS
arm group type: Experimental
description: Transcranial direct current stimulation once time. Dose 2 mA, 20 seconds.
intervention type: Device
intervention name: Transcranial Direct Current Stimulation (tDCS)
arm group label: tDCS
intervention type: Drug
intervention name: Melatonin
arm group label: Melatonin
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Wolnei Caumo
role: Principal Investigator
affiliation: Hospital de Clinicas de Porto Alegre - UFRGS
last name: Wolnei Caumo, PhD
phone: 555133598083
email: caumo@cpovo.net
last name: Nadia Jardim, MD
phone: 555133598083
email: nrjs@ufpa.br
facility: 
status: Recruiting
contact: 
investigator: 
country: Brazil
responsible party type: Sponsor
mesh term: Melatonin