<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/NCT03005548</url>
  </required_header>
  <id_info>
    <org_study_id>MF-VMA// 07.12.2015.</org_study_id>
    <nct_id>NCT03005548</nct_id>
  </id_info>
  <brief_title>Cortical Modulation of Acute Post-thoracotomy Pain With Transcranial Direct Current Stimulation</brief_title>
  <acronym>CMAPTPtDCS</acronym>
  <official_title>Cortical Modulation of Acute Post-thoracotomy Pain With Transcranial Direct Current Stimulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Military Medical Academy, Belgrade, Serbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Military Medical Academy, Belgrade, Serbia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this single center, prospective, randomized, double blind clinical&#xD;
      trial is to evaluate the effectiveness of anodal transcranial direct current stimulation&#xD;
      (tDCS) combined with patient controlled analgesia (PCA) morphine, on intravenous morphine use&#xD;
      for postoperative analgesia after thoracotomy. The intervention group will receive treatment&#xD;
      with anodal tDCS, whereas the control group will receive sham stimulation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      tDCS has been used for treatment of chronic pain states, but experience with the use of tDCS&#xD;
      for treatment of acute postoperative pain is limited. tDCS has been used for postoperative&#xD;
      analgesia after lumbar spine surgery, total knee arthroplasty and for post-procedural pain&#xD;
      after endoscopic retrograde cholangiopancreatography.&#xD;
&#xD;
      This study investigates the effects of tDCS vs. sham stimulation combined with IV morphine&#xD;
      PCA on postoperative morphine consumption for analgesia after thoracotomy for lung cancer.&#xD;
&#xD;
      Patients with malignant lung disease requiring thoracotomy will be randomly assigned to&#xD;
      active stimulation or sham stimulation in a double-blind, sham-controlled, parallel design&#xD;
      clinical trial. Each group will receive IV morphine PCA and tDCS vs. IV morphine PCA and sham&#xD;
      stimulation daily, starting with arrival in the post-anesthesia care unit on the day of&#xD;
      surgery and continuing for the first four postoperative days. Anodal tDCS with direct current&#xD;
      at intensity 2 mA will be delivered for 20 minutes on five consecutive days, whereas sham&#xD;
      stimulation will last for 30 seconds.&#xD;
&#xD;
      Morphine consumption, the number of analgesia demands, and pain intensity at rest, during&#xD;
      movement and with cough will be recorded at predetermined time intervals as follows: After&#xD;
      surgery, when VAS pain score at rest falls below 30 mm, tDCS will be applied. VAS pain will&#xD;
      be measured immediately before the intervention (T0) and immediately after the intervention&#xD;
      (T1), and then regularly every one hour for the four hours (Т2-Т5), and then every six hours&#xD;
      (Т6-Т9) for five days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2016</start_date>
  <completion_date type="Actual">January 2018</completion_date>
  <primary_completion_date type="Actual">December 2017</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>Amount of morphine used for treatment of pain after thoracotomy in a group of patients receiving tDCS combined with intravenous morphine PCA compared with a group of patients receiving sham stimulation combined with intravenous morphine PCA.</measure>
    <time_frame>Five days</time_frame>
    <description>Daily during five postoperative days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain scores measured using visual analogue scale (VAS) at rest, during movement and during cough in patients receiving tDCS combined and IV morphine PCA compared with patients receiving sham stimulation and IV morphine PCA.</measure>
    <time_frame>Five days</time_frame>
    <description>After surgery, when VAS pain score at rest falls below 30 mm, tDCS will be applied. VAS pain will be measured immediately before the intervention (T0) and immediately after the intervention (T1), and then regularly every one hour for the four hours (Т2-Т5), and then every six hours (Т6-Т9) for five days.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Pain, Postoperative</condition>
  <arm_group>
    <arm_group_label>Active tDCS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental: Transcranial direct current stimulation (tDCS). Patients assigned to the active treatment group (n=31) will receive IV morphine followed by IV morphine PCA (IV morphine bolus 1 mg, lockout time 10 mins.), preceded by tDCS (20 minutes of 2 milliamperes (mA) anodal tDCS over the ipsilateral cortex for 5days/week).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham tDCS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham Control Group: Patients assigned to the control group (n=31) will receive IV morphine followed by IV morphine PCA (IV morphine bolus 1 mg, lockout time 10 mins.), preceded by sham tDCS stimulation (30 sec over the ipsilateral cortex, 5 days/week).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial direct current stimulation</intervention_name>
    <description>Transcranial direct current stimulation. All eligible patients will be treated with patient-controlled IV morphine analgesia by PCA (PCA pump (CADD-Legacy PCA Pump, Deltec, Inc.) IV morphine bolus 1 mg, lockout time 10 mins.).&#xD;
Device: wireless tDCS (StarStim, NeuroElectrics) non-invasive brain stimulation with a pair of electrodes with saline-soaked pads for delivery of direct current at intensity 2 mA for 20 mins.</description>
    <arm_group_label>Active tDCS</arm_group_label>
    <other_name>tDCS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine</intervention_name>
    <description>In Sham comparator group All eligible patients will be treated with patient-controlled IV morphine analgesia (PCA) (PCA pump (CADD-Legacy PCA Pump (Deltec, Inc.) morphine IV bolus 1 mg, lockout time 10 mins).&#xD;
Device: wireless tDCS (StarStim, NeuroElectrics) non-invasive brain stimulation with a pair of electrodes with saline-soaked pads for delivery of direct current at intensity 2 mA for 30s at the beginning.</description>
    <arm_group_label>Active tDCS</arm_group_label>
    <arm_group_label>Sham tDCS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject is willing and able to provide written informed consent,&#xD;
&#xD;
          -  Subject is 18-80 years old,&#xD;
&#xD;
          -  Subject needs thoracotomy for confirmed malignant lung disease,&#xD;
&#xD;
          -  Subject is extubated in the operating room&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject is pregnant&#xD;
&#xD;
          -  Subject is in treatment for psychiatric disease&#xD;
&#xD;
          -  Subject is in treatment for neurological disease&#xD;
&#xD;
          -  Subject is in treatment for chronic pain&#xD;
&#xD;
          -  Subject has history of current or past alcohol or Street Drug abuse&#xD;
&#xD;
          -  Subject has received chemotherapy&#xD;
&#xD;
          -  Subject has history of previous thoracic or cardiac surgery&#xD;
&#xD;
          -  Subject is allergic to medications that will be used in the study&#xD;
&#xD;
          -  Subject has pacemaker or automatic implantable cardioverter/defibrillator&#xD;
&#xD;
          -  Subject has implants or any other devices in the head, the spinal cord or peripheral&#xD;
             nerves&#xD;
&#xD;
          -  Subject has confirmed brain lesion, including tumor or metastasis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tihomir V Ilic, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Military Medical Academy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dusica M Stamenkovic, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Military Medical Academy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Military Medical Academy, Department of Anesthesiology</name>
      <address>
        <city>Belgrade</city>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Serbia</country>
  </location_countries>
  <results_reference>
    <citation>Dubois PE, Ossemann M, de Fays K, De Bue P, Gourdin M, Jamart J, Vandermeeren Y. Postoperative analgesic effect of transcranial direct current stimulation in lumbar spine surgery: a randomized control trial. Clin J Pain. 2013 Aug;29(8):696-701. doi: 10.1097/AJP.0b013e31826fb302.</citation>
    <PMID>23719070</PMID>
  </results_reference>
  <results_reference>
    <citation>Borckardt JJ, Reeves ST, Robinson SM, May JT, Epperson TI, Gunselman RJ, Schutte HD, Demos HA, Madan A, Fredrich S, George MS. Transcranial direct current stimulation (tDCS) reduces postsurgical opioid consumption in total knee arthroplasty (TKA). Clin J Pain. 2013 Nov;29(11):925-8. doi: 10.1097/AJP.0b013e31827e32be.</citation>
    <PMID>23370085</PMID>
  </results_reference>
  <results_reference>
    <citation>Borckardt JJ, Romagnuolo J, Reeves ST, Madan A, Frohman H, Beam W, George MS. Feasibility, safety, and effectiveness of transcranial direct current stimulation for decreasing post-ERCP pain: a randomized, sham-controlled, pilot study. Gastrointest Endosc. 2011 Jun;73(6):1158-64. doi: 10.1016/j.gie.2011.01.050. Epub 2011 Apr 5.</citation>
    <PMID>21470608</PMID>
  </results_reference>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>December 24, 2016</study_first_submitted>
  <study_first_submitted_qc>December 24, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>March 27, 2018</last_update_submitted>
  <last_update_submitted_qc>March 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Military Medical Academy, Belgrade, Serbia</investigator_affiliation>
    <investigator_full_name>Dusica Stamenkovic</investigator_full_name>
    <investigator_title>Associate Professor, MD, PhD, Anesthesiologist</investigator_title>
  </responsible_party>
  <keyword>Transcranial Direct Current Stimulation</keyword>
  <keyword>Pain Postoperative</keyword>
  <keyword>Thoracotomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Morphine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03005548
org study id: MF-VMA// 07.12.2015.
nct id: NCT03005548
lead sponsor: 
has dmc: Yes
The primary objective of this single center, prospective, randomized, double blind clinical
      trial is to evaluate the effectiveness of anodal transcranial direct current stimulation
      (tDCS) combined with patient controlled analgesia (PCA) morphine, on intravenous morphine use
      for postoperative analgesia after thoracotomy. The intervention group will receive treatment
      with anodal tDCS, whereas the control group will receive sham stimulation.
tDCS has been used for treatment of chronic pain states, but experience with the use of tDCS
      for treatment of acute postoperative pain is limited. tDCS has been used for postoperative
      analgesia after lumbar spine surgery, total knee arthroplasty and for post-procedural pain
      after endoscopic retrograde cholangiopancreatography.

      This study investigates the effects of tDCS vs. sham stimulation combined with IV morphine
      PCA on postoperative morphine consumption for analgesia after thoracotomy for lung cancer.

      Patients with malignant lung disease requiring thoracotomy will be randomly assigned to
      active stimulation or sham stimulation in a double-blind, sham-controlled, parallel design
      clinical trial. Each group will receive IV morphine PCA and tDCS vs. IV morphine PCA and sham
      stimulation daily, starting with arrival in the post-anesthesia care unit on the day of
      surgery and continuing for the first four postoperative days. Anodal tDCS with direct current
      at intensity 2 mA will be delivered for 20 minutes on five consecutive days, whereas sham
      stimulation will last for 30 seconds.

      Morphine consumption, the number of analgesia demands, and pain intensity at rest, during
      movement and with cough will be recorded at predetermined time intervals as follows: After
      surgery, when VAS pain score at rest falls below 30 mm, tDCS will be applied. VAS pain will
      be measured immediately before the intervention (T0) and immediately after the intervention
      (T1), and then regularly every one hour for the four hours (Т2-Т5), and then every six hours
      (Т6-Т9) for five days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Amount of morphine used for treatment of pain after thoracotomy in a group of patients receiving tDCS combined with intravenous morphine PCA compared with a group of patients receiving sham stimulation combined with intravenous morphine PCA.
time frame: Five days
description: Daily during five postoperative days
measure: Pain scores measured using visual analogue scale (VAS) at rest, during movement and during cough in patients receiving tDCS combined and IV morphine PCA compared with patients receiving sham stimulation and IV morphine PCA.
time frame: Five days
description: After surgery, when VAS pain score at rest falls below 30 mm, tDCS will be applied. VAS pain will be measured immediately before the intervention (T0) and immediately after the intervention (T1), and then regularly every one hour for the four hours (Т2-Т5), and then every six hours (Т6-Т9) for five days.
arm group label: Active tDCS
arm group type: Experimental
description: Experimental: Transcranial direct current stimulation (tDCS). Patients assigned to the active treatment group (n=31) will receive IV morphine followed by IV morphine PCA (IV morphine bolus 1 mg, lockout time 10 mins.), preceded by tDCS (20 minutes of 2 milliamperes (mA) anodal tDCS over the ipsilateral cortex for 5days/week).
arm group label: Sham tDCS
arm group type: Sham Comparator
description: Sham Control Group: Patients assigned to the control group (n=31) will receive IV morphine followed by IV morphine PCA (IV morphine bolus 1 mg, lockout time 10 mins.), preceded by sham tDCS stimulation (30 sec over the ipsilateral cortex, 5 days/week).
intervention type: Device
intervention name: Transcranial direct current stimulation
description: Transcranial direct current stimulation. All eligible patients will be treated with patient-controlled IV morphine analgesia by PCA (PCA pump (CADD-Legacy PCA Pump, Deltec, Inc.) IV morphine bolus 1 mg, lockout time 10 mins.).
Device: wireless tDCS (StarStim, NeuroElectrics) non-invasive brain stimulation with a pair of electrodes with saline-soaked pads for delivery of direct current at intensity 2 mA for 20 mins.
arm group label: Active tDCS
other name: tDCS
intervention type: Drug
intervention name: Morphine
description: In Sham comparator group All eligible patients will be treated with patient-controlled IV morphine analgesia (PCA) (PCA pump (CADD-Legacy PCA Pump (Deltec, Inc.) morphine IV bolus 1 mg, lockout time 10 mins).
Device: wireless tDCS (StarStim, NeuroElectrics) non-invasive brain stimulation with a pair of electrodes with saline-soaked pads for delivery of direct current at intensity 2 mA for 30s at the beginning.
arm group label: Active tDCS
arm group label: Sham tDCS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Tihomir V Ilic, MD, PhD
role: Study Chair
affiliation: Military Medical Academy
last name: Dusica M Stamenkovic, MD, PhD
role: Principal Investigator
affiliation: Military Medical Academy
facility: 
country: Serbia
citation: Dubois PE, Ossemann M, de Fays K, De Bue P, Gourdin M, Jamart J, Vandermeeren Y. Postoperative analgesic effect of transcranial direct current stimulation in lumbar spine surgery: a randomized control trial. Clin J Pain. 2013 Aug;29(8):696-701. doi: 10.1097/AJP.0b013e31826fb302.
PMID: 23719070
citation: Borckardt JJ, Reeves ST, Robinson SM, May JT, Epperson TI, Gunselman RJ, Schutte HD, Demos HA, Madan A, Fredrich S, George MS. Transcranial direct current stimulation (tDCS) reduces postsurgical opioid consumption in total knee arthroplasty (TKA). Clin J Pain. 2013 Nov;29(11):925-8. doi: 10.1097/AJP.0b013e31827e32be.
PMID: 23370085
citation: Borckardt JJ, Romagnuolo J, Reeves ST, Madan A, Frohman H, Beam W, George MS. Feasibility, safety, and effectiveness of transcranial direct current stimulation for decreasing post-ERCP pain: a randomized, sham-controlled, pilot study. Gastrointest Endosc. 2011 Jun;73(6):1158-64. doi: 10.1016/j.gie.2011.01.050. Epub 2011 Apr 5.
PMID: 21470608
responsible party type: Principal Investigator
investigator affiliation: Military Medical Academy, Belgrade, Serbia
investigator full name: Dusica Stamenkovic
investigator title: Associate Professor, MD, PhD, Anesthesiologist
mesh term: Pain, Postoperative
mesh term: Morphine
sharing ipd: Undecided