<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/NCT03773926</url>
  </required_header>
  <id_info>
    <org_study_id>2018-A00604-51</org_study_id>
    <nct_id>NCT03773926</nct_id>
  </id_info>
  <brief_title>Neuro-feedback Therapy for Treating Tinnitus</brief_title>
  <acronym>TNTA</acronym>
  <official_title>Neuro-feedback Therapy for Treating Tinnitus : Efficacy Pilot Study on a Targeted Population</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zeta Technologies</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital, Toulouse</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Zeta Technologies</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Neuro-feedback for treating tinnitus seem to be a promising approach to help people suffering&#xD;
      from chronic tinnitus. The past studies on this approach suffered interindividual variability&#xD;
      in their results. The investigators' current hypothesis is that the variability of the&#xD;
      results is the consequences of two possible flaws: lack of appropriate patient selection and&#xD;
      lack of support of the patient during the therapy. This study is aimed at testing these&#xD;
      hypotheses.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Many individuals with tinnitus have abnormal oscillatory brain activity in their temporal&#xD;
      areas (Weisz et al. (2005), Schlee et al. (2014)). Led by this finding, attempts to normalize&#xD;
      such localized pathological activity by neuro-feedback techniques have been tested (Dohrmann&#xD;
      et al. (2007), Gütenspenger et al. (2017)). These attempts highlighted interindividual&#xD;
      variability that can be explained by lack of selection of the patient population and lack of&#xD;
      guidance through the therapy. The present study is aimed at addressing these issues by&#xD;
      choosing more selectively a patient subpopulation (tinnitus associated with moderate hearing&#xD;
      loss) and by implementing a guidance interface during the treatment.&#xD;
&#xD;
      The therapy will consist of 10 neuro-feedback training sessions of 29 minutes over 5 weeks.&#xD;
      Each session will be composed of 6 blocks of 3 min in which the patient will be incited to&#xD;
      practise a specific cognitive strategy (mental exercise such as &quot;think to a music you like&quot;)&#xD;
      and resting state measurements.&#xD;
&#xD;
      Each patient who has been recruited to fit our inclusion and non-inclusion criteria will&#xD;
      first go through a clinical assessment of his initial judgment criteria metrics. Then&#xD;
      subjects will go through the 5-week training and then will be evaluated on the same criteria&#xD;
      just after the end of the therapy and at 3 months after the end of it.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 28, 2018</start_date>
  <completion_date type="Anticipated">January 15, 2019</completion_date>
  <primary_completion_date type="Anticipated">January 15, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>An efficiency multicentric pilot study on a targeted population for development and use of Neuro-feedback therapy for treating tinnitus.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison of initial and final Tinnitus Handicap Inventory (THI) distributions</measure>
    <time_frame>Comparison of initial and final THI before and after treatment for a Time frame of 5 weeks.</time_frame>
    <description>This primary outcome measure denotes the evolution of the deterioration of the quality of life of patients due to tinnitus. THI is a questionnaire composed of 25 questions each with 3 response options converting in 0, 2, and 4 points scoring, making it a scale from 0 to 100 points.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of initial and final Visual Analog Scale (VAS) distributions</measure>
    <time_frame>Comparison of initial and final VAS before and after treatment for a Time frame of 5 weeks.</time_frame>
    <description>The secondary outcome measure denotes the evolution of the intensity of tinnitus and the disturbance associated measured by two scales. First the Visual Analog Scale (VAS) for intensity of Tinnitus enables the patient to rate his tinnitus intensity with integers values between 1 to 10 (included). Second, the Visual Analog Scale (VAS) for Tinnitus associated disturbance enables the patient to rate his tinnitus associated diturbance with integers values between 1 to 10 (included). For both scales, a high value (near 10) indicates a high gravity of the symptom, regarding either its intensity or its associated disturbance, while low values (near 1), indicate lighter impact of the symptom regarding its intensity or its associated disturbance. The scores are assessed subjectively by the patient when asked.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of Tinnitus Handicap Inventory (THI) and Visual Analog Scales (VAS) on tinnitus intensity and associated disturbance 3 month after the treatment</measure>
    <time_frame>3 months after the end of the 5 week treatment</time_frame>
    <description>Evaluation of maintenance of effects perceived 3 months after the treatment. The THI and the VAS scales are used similarly to the precedent outcome measures. THI is a questionnaire composed of 25 questions each with 3 response options converting in 0, 2, and 4 points scoring, making it a scale from 0 to 100 points. the Visual Analog Scale (VAS) for intensity of Tinnitus enables the patient to rate his tinnitus intensity with integers values between 1 to 10 (included). The Visual Analog Scale (VAS) for Tinnitus associated disturbance enables the patient to rate his tinnitus associated diturbance with integers values between 1 to 10 (included). For both visual analog scales, a high value (near 10) indicates a high gravity of the symptom, regarding either its intensity or its associated disturbance, while low values (near 1), indicate lighter impact of the symptom regarding its intensity or its associated disturbance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side effects</measure>
    <time_frame>The total duration of the study</time_frame>
    <description>Evaluation of potential side effects during the study. At each session patients will be asked if they want to declare any side effects they believe to be related to the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of pathological attention level (BAHIA) standing for (in french) Biphasique, Acouphène, Hyperacousie, Insensibilité de la face et Autres sensations.</measure>
    <time_frame>Comparison of initial and final BAHIA before and after treatment for a Time frame of 5 weeks.</time_frame>
    <description>Evaluation of the proportion of daily time that the patient reports experiencing and being disturbed by his tinnitus through 4 questions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of the electrophysiological measurements and the THI/VAS measurements</measure>
    <time_frame>Over the 5 weeks of treatment</time_frame>
    <description>Correlation between the plastic effects induced by therapy on electrophysiological measurements and the assessment of the severity of tinnitus through the THI/VAS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of the THI, BAHIA, and VAS scores, expressed as a percentage of the initial value</measure>
    <time_frame>Comparison of initial and final measurements before and after treatment for a Time frame of 5 weeks.</time_frame>
    <description>Evolution of the precedent quoted measures before and after treatment measured as percentages of the initial value (proportion of evolution of the THI, VAS and BAHIA measurements).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Tinnitus</condition>
  <condition>Hearing Loss</condition>
  <arm_group>
    <arm_group_label>Neuro-feedback therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EEG headset is placed on the patients head and the electrodes record the brain activity from F3, F4, FC1 and FC2 (on the 10-10 international localization system of EEG electrodes) and generate feedback.&#xD;
Each session is composed of 6 blocks of 3 minutes in which the patient is incited to practice a specific cognitive strategy. During the 4 first session, 8 strategies are explored. Then through the therapy, the best cognitive strategies are gradually selected through an automatized process taking in account objective performances and subjective feedback.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Neuro-feedback therapy</intervention_name>
    <description>The therapy consists of 10 Neuro-feedback training sessions, 2 times per week over 5 weeks.</description>
    <arm_group_label>Neuro-feedback therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria :&#xD;
&#xD;
          -  Age &gt; 18&#xD;
&#xD;
          -  Social security affiliation&#xD;
&#xD;
          -  Permanent, non-fluctuation, high pitch, bilateral or assimilated, tinnitus&#xD;
&#xD;
          -  Mean value of the VAS at least at 6 between the intensity and the disturbance criteria&#xD;
             at the recruitment interview.&#xD;
&#xD;
          -  THI score superior or equal to 40 at the recruitment interview&#xD;
&#xD;
          -  Written consent to the protocol&#xD;
&#xD;
          -  Associated hearing-loss characterized by :&#xD;
&#xD;
          -  mean value of the hearing threshold loss for the 250, 500 and 1000 Hz thresholds&#xD;
             strictly under 25 dB (deciBel).&#xD;
&#xD;
          -  at least one hearing threshold among the 2000, 4000, 6000 and 8000 Hz with at least 30&#xD;
             dB of hearing loss.&#xD;
&#xD;
          -  mean value of the hearing threshold loss for the 2000, 4000, 6000 and 8000 Hz&#xD;
             thresholds strictly under 70 dB.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects under legal protection (guardianship, trusteeship or judicial protection)&#xD;
&#xD;
          -  Notable cognitive disability impeding to understanding or performing the cognitive&#xD;
             tasks&#xD;
&#xD;
          -  Meniere's disease, chronic or serous otitis, acoustic neuroma&#xD;
&#xD;
          -  Pulsatile tinnitus, somatosensorial tinnitus&#xD;
&#xD;
          -  Epilepsy&#xD;
&#xD;
          -  No antidepressant or anti-epileptic drug treatment&#xD;
&#xD;
          -  DET (DETresse) questionnaire (measure of tinnitus associated distress) above or equal&#xD;
             to 40&#xD;
&#xD;
          -  Use of a sound generator during the therapy&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Inability to wear the electrodes headset of the neuro-feedback device&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marie-Josée FRAYSSE</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Toulouse</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alain LONDERO</last_name>
    <phone>05 61 77 21 19</phone>
    <email>Alain.londero@aphp.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Renaud SIMEON</last_name>
    <phone>01 40 19 36 61</phone>
    <email>r.simeon@ch-bry.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Audika Research Center</name>
      <address>
        <city>Paris</city>
        <state>Ile De France</state>
        <zip>75005</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>ROBIN GUILLARD</last_name>
      <phone>0033642480836</phone>
      <email>r@zetatech.fr</email>
    </contact>
    <contact_backup>
      <last_name>THOMAS CERVONI</last_name>
      <phone>0033638895203</phone>
      <email>t@zetatech.fr</email>
    </contact_backup>
    <investigator>
      <last_name>ALAIN LONDERO</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>RENAUD SIMEON</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Purpan University hospital</name>
      <address>
        <city>Toulouse</city>
        <state>Languedoc-Roussillon-Midi-Pyrénées</state>
        <zip>31300</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jonathan SCHMUTZ</last_name>
      <phone>0033634390378</phone>
      <email>j@zetatech.fr</email>
    </contact>
    <contact_backup>
      <last_name>Agnès AGASSE</last_name>
      <phone>00335 61 77 77 70</phone>
    </contact_backup>
    <investigator>
      <last_name>Marie-Josée FRAYSSE</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <link>
    <url>https://www.hindawi.com/journals/np/2014/436146/</url>
    <description>Reduced Variability of Auditory Alpha Activity in Chronic Tinnitus</description>
  </link>
  <reference>
    <citation>Crocetti A, Forti S, Del Bo L. Neurofeedback for subjective tinnitus patients. Auris Nasus Larynx. 2011 Dec;38(6):735-8. doi: 10.1016/j.anl.2011.02.003. Epub 2011 May 17.</citation>
    <PMID>21592701</PMID>
  </reference>
  <reference>
    <citation>Dohrmann K, Weisz N, Schlee W, Hartmann T, Elbert T. Neurofeedback for treating tinnitus. Prog Brain Res. 2007;166:473-85. doi: 10.1016/S0079-6123(07)66046-4.</citation>
    <PMID>17956812</PMID>
  </reference>
  <reference>
    <citation>Hartmann T, Lorenz I, Muller N, Langguth B, Weisz N. The effects of neurofeedback on oscillatory processes related to tinnitus. Brain Topogr. 2014 Jan;27(1):149-57. doi: 10.1007/s10548-013-0295-9. Epub 2013 May 23.</citation>
    <PMID>23700271</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>October 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>December 11, 2018</last_update_submitted>
  <last_update_submitted_qc>December 11, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Tinnitus</keyword>
  <keyword>Neuro-feedback</keyword>
  <keyword>Male</keyword>
  <keyword>Female</keyword>
  <keyword>Tinnitus Handicap Inventory</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hearing Loss</mesh_term>
    <mesh_term>Tinnitus</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03773926
org study id: 2018-A00604-51
nct id: NCT03773926
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Neuro-feedback for treating tinnitus seem to be a promising approach to help people suffering
      from chronic tinnitus. The past studies on this approach suffered interindividual variability
      in their results. The investigators' current hypothesis is that the variability of the
      results is the consequences of two possible flaws: lack of appropriate patient selection and
      lack of support of the patient during the therapy. This study is aimed at testing these
      hypotheses.
Many individuals with tinnitus have abnormal oscillatory brain activity in their temporal
      areas (Weisz et al. (2005), Schlee et al. (2014)). Led by this finding, attempts to normalize
      such localized pathological activity by neuro-feedback techniques have been tested (Dohrmann
      et al. (2007), Gütenspenger et al. (2017)). These attempts highlighted interindividual
      variability that can be explained by lack of selection of the patient population and lack of
      guidance through the therapy. The present study is aimed at addressing these issues by
      choosing more selectively a patient subpopulation (tinnitus associated with moderate hearing
      loss) and by implementing a guidance interface during the treatment.

      The therapy will consist of 10 neuro-feedback training sessions of 29 minutes over 5 weeks.
      Each session will be composed of 6 blocks of 3 min in which the patient will be incited to
      practise a specific cognitive strategy (mental exercise such as "think to a music you like")
      and resting state measurements.

      Each patient who has been recruited to fit our inclusion and non-inclusion criteria will
      first go through a clinical assessment of his initial judgment criteria metrics. Then
      subjects will go through the 5-week training and then will be evaluated on the same criteria
      just after the end of the therapy and at 3 months after the end of it.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: An efficiency multicentric pilot study on a targeted population for development and use of Neuro-feedback therapy for treating tinnitus.
primary purpose: Treatment
masking: None (Open Label)
measure: Comparison of initial and final Tinnitus Handicap Inventory (THI) distributions
time frame: Comparison of initial and final THI before and after treatment for a Time frame of 5 weeks.
description: This primary outcome measure denotes the evolution of the deterioration of the quality of life of patients due to tinnitus. THI is a questionnaire composed of 25 questions each with 3 response options converting in 0, 2, and 4 points scoring, making it a scale from 0 to 100 points.
measure: Comparison of initial and final Visual Analog Scale (VAS) distributions
time frame: Comparison of initial and final VAS before and after treatment for a Time frame of 5 weeks.
description: The secondary outcome measure denotes the evolution of the intensity of tinnitus and the disturbance associated measured by two scales. First the Visual Analog Scale (VAS) for intensity of Tinnitus enables the patient to rate his tinnitus intensity with integers values between 1 to 10 (included). Second, the Visual Analog Scale (VAS) for Tinnitus associated disturbance enables the patient to rate his tinnitus associated diturbance with integers values between 1 to 10 (included). For both scales, a high value (near 10) indicates a high gravity of the symptom, regarding either its intensity or its associated disturbance, while low values (near 1), indicate lighter impact of the symptom regarding its intensity or its associated disturbance. The scores are assessed subjectively by the patient when asked.
measure: Evolution of Tinnitus Handicap Inventory (THI) and Visual Analog Scales (VAS) on tinnitus intensity and associated disturbance 3 month after the treatment
time frame: 3 months after the end of the 5 week treatment
description: Evaluation of maintenance of effects perceived 3 months after the treatment. The THI and the VAS scales are used similarly to the precedent outcome measures. THI is a questionnaire composed of 25 questions each with 3 response options converting in 0, 2, and 4 points scoring, making it a scale from 0 to 100 points. the Visual Analog Scale (VAS) for intensity of Tinnitus enables the patient to rate his tinnitus intensity with integers values between 1 to 10 (included). The Visual Analog Scale (VAS) for Tinnitus associated disturbance enables the patient to rate his tinnitus associated diturbance with integers values between 1 to 10 (included). For both visual analog scales, a high value (near 10) indicates a high gravity of the symptom, regarding either its intensity or its associated disturbance, while low values (near 1), indicate lighter impact of the symptom regarding its intensity or its associated disturbance.
measure: Side effects
time frame: The total duration of the study
description: Evaluation of potential side effects during the study. At each session patients will be asked if they want to declare any side effects they believe to be related to the treatment.
measure: Evolution of pathological attention level (BAHIA) standing for (in french) Biphasique, Acouphène, Hyperacousie, Insensibilité de la face et Autres sensations.
time frame: Comparison of initial and final BAHIA before and after treatment for a Time frame of 5 weeks.
description: Evaluation of the proportion of daily time that the patient reports experiencing and being disturbed by his tinnitus through 4 questions.
measure: Correlation of the electrophysiological measurements and the THI/VAS measurements
time frame: Over the 5 weeks of treatment
description: Correlation between the plastic effects induced by therapy on electrophysiological measurements and the assessment of the severity of tinnitus through the THI/VAS.
measure: Evolution of the THI, BAHIA, and VAS scores, expressed as a percentage of the initial value
time frame: Comparison of initial and final measurements before and after treatment for a Time frame of 5 weeks.
description: Evolution of the precedent quoted measures before and after treatment measured as percentages of the initial value (proportion of evolution of the THI, VAS and BAHIA measurements).
arm group label: Neuro-feedback therapy
arm group type: Experimental
description: EEG headset is placed on the patients head and the electrodes record the brain activity from F3, F4, FC1 and FC2 (on the 10-10 international localization system of EEG electrodes) and generate feedback.
Each session is composed of 6 blocks of 3 minutes in which the patient is incited to practice a specific cognitive strategy. During the 4 first session, 8 strategies are explored. Then through the therapy, the best cognitive strategies are gradually selected through an automatized process taking in account objective performances and subjective feedback.
intervention type: Device
intervention name: Neuro-feedback therapy
description: The therapy consists of 10 Neuro-feedback training sessions, 2 times per week over 5 weeks.
arm group label: Neuro-feedback therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marie-Josée FRAYSSE
role: Principal Investigator
affiliation: University Hospital, Toulouse
last name: Alain LONDERO
phone: 05 61 77 21 19
email: Alain.londero@aphp.fr
last name: Renaud SIMEON
phone: 01 40 19 36 61
email: r.simeon@ch-bry.org
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: France
url: https://www.hindawi.com/journals/np/2014/436146/
description: Reduced Variability of Auditory Alpha Activity in Chronic Tinnitus
citation: Crocetti A, Forti S, Del Bo L. Neurofeedback for subjective tinnitus patients. Auris Nasus Larynx. 2011 Dec;38(6):735-8. doi: 10.1016/j.anl.2011.02.003. Epub 2011 May 17.
PMID: 21592701
citation: Dohrmann K, Weisz N, Schlee W, Hartmann T, Elbert T. Neurofeedback for treating tinnitus. Prog Brain Res. 2007;166:473-85. doi: 10.1016/S0079-6123(07)66046-4.
PMID: 17956812
citation: Hartmann T, Lorenz I, Muller N, Langguth B, Weisz N. The effects of neurofeedback on oscillatory processes related to tinnitus. Brain Topogr. 2014 Jan;27(1):149-57. doi: 10.1007/s10548-013-0295-9. Epub 2013 May 23.
PMID: 23700271
responsible party type: Sponsor
mesh term: Hearing Loss
mesh term: Tinnitus
sharing ipd: No