<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/NCT01663324</url>
  </required_header>
  <id_info>
    <org_study_id>Uni-Reg-multisite-rTMS-Tin-01</org_study_id>
    <nct_id>NCT01663324</nct_id>
  </id_info>
  <brief_title>rTMS for the Treatment of Chronic Tinnitus: Optimization by Simulation of the Cortical Tinnitus Network</brief_title>
  <acronym>Multisite rTMS</acronym>
  <official_title>Repetitive Transcranial Magnetic Stimulation for the Treatment of Chronic Tinnitus: Optimization by Stimulation of the Cortical Tinnitus Network</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Regensburg</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Regensburg</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Transcranial Magnetic Stimulation is used to modulate both the auditory and non-auditory&#xD;
      neural pathways contributing to the perception of phantom sounds.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Tinnitus is the phantom auditory perception of sound in the absence of an external or&#xD;
      internal acoustic stimulus. It is a frequent problem which can interfere significantly with&#xD;
      the ability to lead a normal life. Treatment remains difficult. Most available therapies&#xD;
      focus on habituation rather than treating the cause. Tinnitus has been shown to be associated&#xD;
      with functional reorganization of auditory neural pathways and tonotopic maps in the central&#xD;
      auditory system. Consequently, low-frequency Repetitive Transcranial Magnetic Stimulation&#xD;
      (rTMS) applied to the temporoparietal areas has been investigated for the treatment of&#xD;
      tinnitus. Additionally, there is growing evidence that a neural network of both auditory and&#xD;
      non-auditory cortical areas is involved in the pathophysiology of chronic subjective&#xD;
      tinnitus. Targeting several core regions of this network by rTMS might constitute a promising&#xD;
      strategy to enhance treatment effects. A new multisite treatment protocol which is supposed&#xD;
      to have an effect on both auditory and non-auditory cortical areas will be examined with&#xD;
      regard to feasibility, safety and clinical efficacy in patients suffering from chronic&#xD;
      tinnitus in a controlled pilot trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">January 2015</completion_date>
  <primary_completion_date type="Actual">August 2014</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, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of treatment responders (TQ reduction ≥5, contrast baseline versus day 12)</measure>
    <time_frame>Day 12</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of tinnitus severity as measured by the Tinnitus Questionnaire of Goebel&amp;Hiller (contrast baseline versus day 12)</measure>
    <time_frame>Day 12</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of depressive symptoms as measured by the Major Depression Inventory (MDI)</measure>
    <time_frame>Day 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life as measured by the WHOQoL</measure>
    <time_frame>Day 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in hyperacusis as measured by the German questionnaire &quot;Geräuschüberempfindlichkeitsfragebogen&quot;</measure>
    <time_frame>Day 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of treatment responders (TQ reduction ≥5, contrast Baseline versus day 90)</measure>
    <time_frame>Day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of tinnitus severity as measured by the Tinnitus Handicap Inventory (THI) and Tinnitus Severity Scale</measure>
    <time_frame>Day 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of tinnitus severity as measured by the Tinnitus Handicap Inventory (THI) and Tinnitus Severity Scale</measure>
    <time_frame>Day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of tinnitus severity as measured by the Tinnitus Handicap Inventory (THI) and Tinnitus Severity Scale</measure>
    <time_frame>Day 180</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of depressive symptoms as measured by the Major Depression Inventory (MDI)</measure>
    <time_frame>Day 180</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of depressive symptoms as measured by the Major Depression Inventory (MDI)</measure>
    <time_frame>Day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life as measured by the WHOQoL</measure>
    <time_frame>Day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life as measured by the WHOQoL</measure>
    <time_frame>Day 180</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in hyperacusis as measured by the German questionnaire &quot;Geräuschüberempfindlichkeitsfragebogen&quot;</measure>
    <time_frame>Day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in hyperacusis as measured by the German questionnaire &quot;Geräuschüberempfindlichkeitsfragebogen&quot;</measure>
    <time_frame>Day 180</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of treatment responders (TQ reduction ≥5, contrast Baseline versus day 180)</measure>
    <time_frame>Day 180</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of tinnitus severity as measured by the Tinnitus Questionaire of Goebel&amp;Hiller</measure>
    <time_frame>Day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of tinnitus severity as measured by the Tinnitus Questionaire of Goebel&amp;Hiller</measure>
    <time_frame>Day 180</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Chronic Tinnitus</condition>
  <arm_group>
    <arm_group_label>single site rTMS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low frequency temporoparietal transcranial magnetic stimulation&#xD;
Intervention: Device: rTMS intervention 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>multisite rTMS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Combined high frequency dorsolateral prefrontal (unilateral) and low frequency temporoparietal (bilateral) stimulation&#xD;
Intervention: Device: rTMS Intervention 2</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>rTMS intervention 1</intervention_name>
    <description>Low frequency rTMS (Magventure Mag Pro Option) applied over left temporoparietal cortex: 3000 stimuli of 1Hz rTMS (110% motor threshold); 1 minute break after 1000 and 2000 stimuli.&#xD;
Arms: single site rTMS</description>
    <arm_group_label>single site rTMS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>rTMS intervention 2</intervention_name>
    <description>Repetitive transcranial magnetic stimulation (Magventure Mag Pro Option): 1000 stimuli of 20 Hz rTMS over the left DLPFC (110% motor threshold) followed by 1000 stimuli of 1 Hz rTMS over the left temporoparietal cortex (110% motor threshold) followed by 1000 stimuli of 1 Hz rTMS over right temporoparietal cortex (110% motor threshold).&#xD;
Arms: multisite rTMS</description>
    <arm_group_label>multisite rTMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of subjective chronic tinnitus&#xD;
&#xD;
          -  THI &gt; 38&#xD;
&#xD;
          -  Duration of tinnitus more than 6 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Objective tinnitus&#xD;
&#xD;
          -  Treatable cause of the tinnitus&#xD;
&#xD;
          -  Involvement in other treatments for tinnitus at the same time&#xD;
&#xD;
          -  Clinically relevant psychiatric comorbidity&#xD;
&#xD;
          -  Clinically relevant unstable internal or neurological comorbidity&#xD;
&#xD;
          -  History of or evidence of significant brain malformation or neoplasm, head injury&#xD;
&#xD;
          -  Cerebral vascular events&#xD;
&#xD;
          -  Neurodegenerative disorder affecting the brain or prior brain surgery;&#xD;
&#xD;
          -  Metal objects in and around body that can not be removed&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Alcohol or drug abuse&#xD;
&#xD;
          -  Prior treatment with TMS&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Berthold Langguth, MD, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Regensburg, Dept of Psychiatry</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Regensburg- Dept of Psychiatry</name>
      <address>
        <city>Regensburg</city>
        <zip>93053</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <results_reference>
    <citation>Lehner A, Schecklmann M, Greenlee MW, Rupprecht R, Langguth B. Triple-site rTMS for the treatment of chronic tinnitus: a randomized controlled trial. Sci Rep. 2016 Mar 1;6:22302. doi: 10.1038/srep22302.</citation>
    <PMID>26927363</PMID>
  </results_reference>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>July 23, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <last_update_submitted>May 17, 2016</last_update_submitted>
  <last_update_submitted_qc>May 17, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 18, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Regensburg</investigator_affiliation>
    <investigator_full_name>Berthold Langguth, MD, Ph.D.</investigator_full_name>
    <investigator_title>MD, Ph.D.</investigator_title>
  </responsible_party>
  <keyword>Tinnitus</keyword>
  <keyword>chronic subjective Tinnitus</keyword>
  <keyword>transcranial magnetic stimulation</keyword>
  <keyword>rTMS</keyword>
  <keyword>hearing disorders</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tinnitus</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/NCT01663324
org study id: Uni-Reg-multisite-rTMS-Tin-01
nct id: NCT01663324
lead sponsor: 
has dmc: No
Transcranial Magnetic Stimulation is used to modulate both the auditory and non-auditory
      neural pathways contributing to the perception of phantom sounds.
Tinnitus is the phantom auditory perception of sound in the absence of an external or
      internal acoustic stimulus. It is a frequent problem which can interfere significantly with
      the ability to lead a normal life. Treatment remains difficult. Most available therapies
      focus on habituation rather than treating the cause. Tinnitus has been shown to be associated
      with functional reorganization of auditory neural pathways and tonotopic maps in the central
      auditory system. Consequently, low-frequency Repetitive Transcranial Magnetic Stimulation
      (rTMS) applied to the temporoparietal areas has been investigated for the treatment of
      tinnitus. Additionally, there is growing evidence that a neural network of both auditory and
      non-auditory cortical areas is involved in the pathophysiology of chronic subjective
      tinnitus. Targeting several core regions of this network by rTMS might constitute a promising
      strategy to enhance treatment effects. A new multisite treatment protocol which is supposed
      to have an effect on both auditory and non-auditory cortical areas will be examined with
      regard to feasibility, safety and clinical efficacy in patients suffering from chronic
      tinnitus in a controlled pilot trial.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Number of treatment responders (TQ reduction ≥5, contrast baseline versus day 12)
time frame: Day 12
measure: Change of tinnitus severity as measured by the Tinnitus Questionnaire of Goebel&Hiller (contrast baseline versus day 12)
time frame: Day 12
measure: Change of depressive symptoms as measured by the Major Depression Inventory (MDI)
time frame: Day 12
measure: Change in quality of life as measured by the WHOQoL
time frame: Day 12
measure: Change in hyperacusis as measured by the German questionnaire "Geräuschüberempfindlichkeitsfragebogen"
time frame: Day 12
measure: Number of treatment responders (TQ reduction ≥5, contrast Baseline versus day 90)
time frame: Day 90
measure: Change of tinnitus severity as measured by the Tinnitus Handicap Inventory (THI) and Tinnitus Severity Scale
time frame: Day 12
measure: Change of tinnitus severity as measured by the Tinnitus Handicap Inventory (THI) and Tinnitus Severity Scale
time frame: Day 90
measure: Change of tinnitus severity as measured by the Tinnitus Handicap Inventory (THI) and Tinnitus Severity Scale
time frame: Day 180
measure: Change of depressive symptoms as measured by the Major Depression Inventory (MDI)
time frame: Day 180
measure: Change of depressive symptoms as measured by the Major Depression Inventory (MDI)
time frame: Day 90
measure: Change in quality of life as measured by the WHOQoL
time frame: Day 90
measure: Change in quality of life as measured by the WHOQoL
time frame: Day 180
measure: Change in hyperacusis as measured by the German questionnaire "Geräuschüberempfindlichkeitsfragebogen"
time frame: Day 90
measure: Change in hyperacusis as measured by the German questionnaire "Geräuschüberempfindlichkeitsfragebogen"
time frame: Day 180
measure: Number of treatment responders (TQ reduction ≥5, contrast Baseline versus day 180)
time frame: Day 180
measure: Change of tinnitus severity as measured by the Tinnitus Questionaire of Goebel&Hiller
time frame: Day 90
measure: Change of tinnitus severity as measured by the Tinnitus Questionaire of Goebel&Hiller
time frame: Day 180
arm group label: single site rTMS
arm group type: Experimental
description: Low frequency temporoparietal transcranial magnetic stimulation
Intervention: Device: rTMS intervention 1
arm group label: multisite rTMS
arm group type: Experimental
description: Combined high frequency dorsolateral prefrontal (unilateral) and low frequency temporoparietal (bilateral) stimulation
Intervention: Device: rTMS Intervention 2
intervention type: Device
intervention name: rTMS intervention 1
description: Low frequency rTMS (Magventure Mag Pro Option) applied over left temporoparietal cortex: 3000 stimuli of 1Hz rTMS (110% motor threshold); 1 minute break after 1000 and 2000 stimuli.
Arms: single site rTMS
arm group label: single site rTMS
intervention type: Device
intervention name: rTMS intervention 2
description: Repetitive transcranial magnetic stimulation (Magventure Mag Pro Option): 1000 stimuli of 20 Hz rTMS over the left DLPFC (110% motor threshold) followed by 1000 stimuli of 1 Hz rTMS over the left temporoparietal cortex (110% motor threshold) followed by 1000 stimuli of 1 Hz rTMS over right temporoparietal cortex (110% motor threshold).
Arms: multisite rTMS
arm group label: multisite rTMS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Berthold Langguth, MD, Ph.D.
role: Principal Investigator
affiliation: University of Regensburg, Dept of Psychiatry
facility: 
country: Germany
citation: Lehner A, Schecklmann M, Greenlee MW, Rupprecht R, Langguth B. Triple-site rTMS for the treatment of chronic tinnitus: a randomized controlled trial. Sci Rep. 2016 Mar 1;6:22302. doi: 10.1038/srep22302.
PMID: 26927363
responsible party type: Principal Investigator
investigator affiliation: University of Regensburg
investigator full name: Berthold Langguth, MD, Ph.D.
investigator title: MD, Ph.D.
mesh term: Tinnitus