<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/NCT03025386</url>
  </required_header>
  <id_info>
    <org_study_id>9735</org_study_id>
    <nct_id>NCT03025386</nct_id>
  </id_info>
  <brief_title>Establish a Concordance Between the Mismatch Negativity Amplitude and a Score of Logatoms Discrimination</brief_title>
  <acronym>EVODA-ICMN</acronym>
  <official_title>Establish a Concordance Between the Mismatch Negativity Amplitude and a Score of Logatoms Discrimination, Both Highlighting Capacities of Auditory Discrimination, in Adult Cochlear Implant Users</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Montpellier</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>
      A cochlear implant is a device for the rehabilitation of severe to profound hearing loss.&#xD;
      Despite the standardization of surgical procedures and rehabilitation, speech discrimination&#xD;
      performance varied significantly in cochlear implant users and could be improved by early&#xD;
      individualized cares. However, there is no objective method yet to evaluate phonemes&#xD;
      discrimination, especially in infants, which account for more than half of the indications&#xD;
      for implantation. In electroencephalography (EEG), it is possible to highlight the&#xD;
      discrimination of auditory stimuli studying the wave of MisMatch Negativity (MMN). In this&#xD;
      work, this study propose to use the MMN as an objective vocal audiometry method to evaluate&#xD;
      the ability to discriminate phonemes, the smallest units of oral language, in adult cochlear&#xD;
      implant users.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Context of the study Cochlear implant is an effective and recognized long-term solution for&#xD;
      people with severe to profound neurosensory hearing loss. Its principle is to collect sounds&#xD;
      of the environment, to analyze them, to transform them and, using an electrodes array placed&#xD;
      in the cochlea, to transmit them back to the auditory nerve by electrical impulses. With&#xD;
      practice, these are integrated and then recognized by the brain that associates a meaning.&#xD;
      For normal hearing persons, speech recognition involves several time and frequency cues that&#xD;
      the ear is able to decode. However, the cochlear implant distorts and alters some of these&#xD;
      speech cues; the implant easily retransmits the temporal features but the frequency ones are&#xD;
      much deteriorated. Thus, cochlear implant users preferentially use the temporal cues, which&#xD;
      provide truncated and incomplete information, which often results in a lower quality&#xD;
      understanding. Thus, learning or re-learning the language through the cochlear implant is&#xD;
      difficult for the young deaf child as for the deaf adults.&#xD;
&#xD;
      The cochlear implant setting is essentially based on perceptual features. A detection&#xD;
      threshold and a comfort level are fitting according to the perceptions of the patient and&#xD;
      several objective tools. These provide important information but do not on the validity of&#xD;
      the setting to ensure optimal speech understanding. The High Authority of Health suggests&#xD;
      speech therapy in the overall rehabilitation of cochlear implant users. This aims to develop&#xD;
      auditory skills according to four major perceptual axes: detection, identification,&#xD;
      discrimination and understanding of sounds.&#xD;
&#xD;
      Despite these cares, cochlear implant users have speech recognition scores lower than those&#xD;
      of normal-hearing people and have heterogeneous performances. Deafness etiology (auditory&#xD;
      neuropathy, demyelization, ...), integrity of the auditory nerve, position of the electrode&#xD;
      array in the cochlea, cognitive abilities, age implantation, duration of hearing loss,&#xD;
      quality of cortical integration, cerebral plasticity, speech therapy, the family environment,&#xD;
      implant fitting could affect subject performances.&#xD;
&#xD;
      Difficulties in speech understanding may be related to poor discrimination of phonemes, the&#xD;
      smallest units of oral language. These phonemic confusions can be tested in adults by several&#xD;
      tests such as the Phonetically Balanced Kindergarten test (PBK). However, in the very young&#xD;
      child, childs with polyhandicap or the disabled adult, the evaluation of the language is more&#xD;
      delicate and needs a long term.&#xD;
&#xD;
      Several electrophysiological techniques would nevertheless make it possible to objectively&#xD;
      demonstrate the ability to discriminate phonemes in one measure. For example, the mismatch&#xD;
      negativity wave (MMN) reflects a cognitive process showing the discrimination of two&#xD;
      different sounds by the auditory system. It is measurable in adults and children,&#xD;
      automatically and regardless of the level of vigilance. In this study use a MMN protocol to&#xD;
      highlight phonemic discrimination capacities and then link them to subjective performances in&#xD;
      the adult cochlear implant users. The first objective is to establish in these users a&#xD;
      concordance between the amplitude of the MMN and a test of discrimination of logatoms, both&#xD;
      highlighting the capacities of auditory discrimination. The second is to establish a&#xD;
      concordance between the amplitude of the MMN and the scores obtained with the PBK.&#xD;
&#xD;
      Method&#xD;
&#xD;
      A forced choice test will evaluate the discrimination of the most confusing logatoms in the&#xD;
      cochlear implant users, and representative of the French language. The following couples were&#xD;
      selected:&#xD;
&#xD;
        -  &quot; fa &quot; vs &quot; sa &quot;&#xD;
&#xD;
        -  &quot; la &quot; vs &quot; na &quot;&#xD;
&#xD;
        -  &quot; pan &quot; vs &quot; pa &quot;&#xD;
&#xD;
        -  &quot; pa &quot; vs &quot; ta &quot;&#xD;
&#xD;
        -  &quot; pon &quot; vs &quot; po &quot; Each couple of logatoms will be tested twenty times. If the score is&#xD;
           greater than 16/20, the discrimination of logatoms pair will be considered positive. The&#xD;
           test, carried out using Matlab MathWorks software, was automated so that the patient&#xD;
           could do it without the intervention of the experimenter; It remains under its&#xD;
           supervision in order to verify that the test is proceeding normally.&#xD;
&#xD;
      Obtaining the MMN requires a paradigm called &quot;oddball&quot;, during which a &quot;frequent&quot; stimulus is&#xD;
      emitted 80% of the time and a second stimulus called &quot;deviant&quot; is presented only 20% of the&#xD;
      time. The high repetition rate of the frequent stimulus (&quot;pa&quot; for example) creates an&#xD;
      electrophysiological baseline. When a deviant stimulus (&quot;ba&quot; for example) appears, this&#xD;
      introduces a break in the electrophysiological baseline which results in the appearance of a&#xD;
      so-called mismatch negative wave, the MMN. It shows the discrimination by the auditory system&#xD;
      of two different stimuli. By studying the amplitude of this wave, it is possible to evaluate&#xD;
      the quality of discrimination. A low or zero amplitude means that the subject did not&#xD;
      discriminate the two logatoms. Conversely, the higher the amplitude, the greater the&#xD;
      discrimination quality is. The wave latency can also be a variable to be observed. The&#xD;
      earlier it is, the more it marks the ease of discrimination.&#xD;
&#xD;
      For each subject, the concordance with the score in the logatoms discrimination test will be&#xD;
      analyzed separately for each pair. This will make it possible to evaluate the consistency of&#xD;
      this concordance according to the pairs of tested logatoms. The optimal threshold of the MMN&#xD;
      amplitude to identify subjects with good auditory discrimination is not yet known (innovative&#xD;
      method). The first stage of our analysis will be to search for this threshold by constructing&#xD;
      an receiver operating characteristic (ROC) curve to best distinguish patients with good and&#xD;
      bad auditory discrimination in the test of the logatoms (choice of the threshold by the index&#xD;
      of Youden). This threshold will then be used to classify subjects as having good or poor&#xD;
      auditory discrimination according to the EEG. The agreement between the results of the EEG&#xD;
      and the test of logatoms discrimination will then be analyzed by the calculation of a Kappa&#xD;
      coefficient.&#xD;
&#xD;
      The PBK test will be used to evaluate an overall comprehension score. This test consists of 4&#xD;
      lists of 50 words respecting the occurrence of the phonemes of the French language and using&#xD;
      mono- and bi-syllabic words. A score above 70% is accepted as a good performance. The&#xD;
      concordance between the results of the EEG procedure for each logatoms (good and bad auditory&#xD;
      discrimination defined as above) and the result of the PBK test will be analyzed using Kappa&#xD;
      coefficients.&#xD;
&#xD;
      Finally, different secondary data will be collected: type of cochlear implant (mark, internal&#xD;
      and external part), duration of implantation in months, etiology, data related to the implant&#xD;
      setting (number of active electrodes , Thresholds C and T, IDR, automatic functions like&#xD;
      SCAN, ADRO, ...)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 18, 2017</start_date>
  <completion_date type="Anticipated">February 2023</completion_date>
  <primary_completion_date type="Anticipated">January 2023</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>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between MMN amplitude and logatoms discrimination score in the discrimination capacity</measure>
    <time_frame>30 days</time_frame>
    <description>The discrimination capacity (positive/ negative) defined by an MMN amplitude above a threshold will be estimated using a ROC curve based on the logatoms discrimination scores The discrimination capacity defined by logatoms test will be positive if the discrimination score is higher or equal to 80%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between MMN amplitude and the Phonetically Balanced Kindergarten score and Vocoder test</measure>
    <time_frame>within the first 30 days after the first visit</time_frame>
    <description>The discrimination capacity will be positive if the correlation score is higher or equal to 70%.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">47</enrollment>
  <condition>Cochlear Implant</condition>
  <arm_group>
    <arm_group_label>Adult cochlear implant users</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Evaluation of a concordance between the mismatch negativity amplitude mesured by electroencephalography and the capacity of logatoms discrimination by using a logatoms test</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>logatoms test</intervention_name>
    <description>A forced choice test will evaluate the discrimination of the most confusing logatoms in the cochlear implant users, and representative of the French language.</description>
    <arm_group_label>Adult cochlear implant users</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Electroencephalography</intervention_name>
    <description>Mesure of the mismatch negativity wave</description>
    <arm_group_label>Adult cochlear implant users</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Aged from 18 to 75&#xD;
&#xD;
          -  Severe to profound deafness&#xD;
&#xD;
          -  Cochlear implant user for over a year&#xD;
&#xD;
          -  Affiliation or beneficiary of the social insurance&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Phonetically balanced kindergarten score less than 25%&#xD;
&#xD;
          -  No steady setting&#xD;
&#xD;
          -  Contralateral hearing aid&#xD;
&#xD;
          -  Electroacoustic stimulation device or bilateral cochlear implant user&#xD;
&#xD;
          -  Inactive electrodes &gt; 3&#xD;
&#xD;
          -  Cochlear Implant wore less than 7 hours per day&#xD;
&#xD;
          -  Disorders of memory, attention or executive functions&#xD;
&#xD;
          -  Associated disorders with deafness&#xD;
&#xD;
          -  No informed consent&#xD;
&#xD;
          -  Patient participating in other biomedical research&#xD;
&#xD;
          -  Patient who has undergone cochlear reimplantation or brain surgery&#xD;
&#xD;
          -  Withdrawal of consents&#xD;
&#xD;
          -  Patient lost to follow-up&#xD;
&#xD;
          -  Death&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frédéric VENAIL, PH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Montpellier</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Frédéric VENAIL, PH</last_name>
    <phone>0467336800</phone>
    <phone_ext>+33</phone_ext>
    <email>f-venail@chu-montpellier.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Antoine LORENZI</last_name>
    <email>a-lorenzi@chu-montpellier.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CHU Montpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>VENAIL Frédéric, PUPH</last_name>
      <email>f-venail@chu-montpellier.fr</email>
    </contact>
    <contact_backup>
      <last_name>LORENZI Antoine</last_name>
      <email>a-lorenzi@chu-montpellier.fr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>January 16, 2017</study_first_submitted>
  <study_first_submitted_qc>January 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 19, 2017</study_first_posted>
  <last_update_submitted>January 13, 2023</last_update_submitted>
  <last_update_submitted_qc>January 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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/NCT03025386
org study id: 9735
nct id: NCT03025386
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A cochlear implant is a device for the rehabilitation of severe to profound hearing loss.
      Despite the standardization of surgical procedures and rehabilitation, speech discrimination
      performance varied significantly in cochlear implant users and could be improved by early
      individualized cares. However, there is no objective method yet to evaluate phonemes
      discrimination, especially in infants, which account for more than half of the indications
      for implantation. In electroencephalography (EEG), it is possible to highlight the
      discrimination of auditory stimuli studying the wave of MisMatch Negativity (MMN). In this
      work, this study propose to use the MMN as an objective vocal audiometry method to evaluate
      the ability to discriminate phonemes, the smallest units of oral language, in adult cochlear
      implant users.
Context of the study Cochlear implant is an effective and recognized long-term solution for
      people with severe to profound neurosensory hearing loss. Its principle is to collect sounds
      of the environment, to analyze them, to transform them and, using an electrodes array placed
      in the cochlea, to transmit them back to the auditory nerve by electrical impulses. With
      practice, these are integrated and then recognized by the brain that associates a meaning.
      For normal hearing persons, speech recognition involves several time and frequency cues that
      the ear is able to decode. However, the cochlear implant distorts and alters some of these
      speech cues; the implant easily retransmits the temporal features but the frequency ones are
      much deteriorated. Thus, cochlear implant users preferentially use the temporal cues, which
      provide truncated and incomplete information, which often results in a lower quality
      understanding. Thus, learning or re-learning the language through the cochlear implant is
      difficult for the young deaf child as for the deaf adults.

      The cochlear implant setting is essentially based on perceptual features. A detection
      threshold and a comfort level are fitting according to the perceptions of the patient and
      several objective tools. These provide important information but do not on the validity of
      the setting to ensure optimal speech understanding. The High Authority of Health suggests
      speech therapy in the overall rehabilitation of cochlear implant users. This aims to develop
      auditory skills according to four major perceptual axes: detection, identification,
      discrimination and understanding of sounds.

      Despite these cares, cochlear implant users have speech recognition scores lower than those
      of normal-hearing people and have heterogeneous performances. Deafness etiology (auditory
      neuropathy, demyelization, ...), integrity of the auditory nerve, position of the electrode
      array in the cochlea, cognitive abilities, age implantation, duration of hearing loss,
      quality of cortical integration, cerebral plasticity, speech therapy, the family environment,
      implant fitting could affect subject performances.

      Difficulties in speech understanding may be related to poor discrimination of phonemes, the
      smallest units of oral language. These phonemic confusions can be tested in adults by several
      tests such as the Phonetically Balanced Kindergarten test (PBK). However, in the very young
      child, childs with polyhandicap or the disabled adult, the evaluation of the language is more
      delicate and needs a long term.

      Several electrophysiological techniques would nevertheless make it possible to objectively
      demonstrate the ability to discriminate phonemes in one measure. For example, the mismatch
      negativity wave (MMN) reflects a cognitive process showing the discrimination of two
      different sounds by the auditory system. It is measurable in adults and children,
      automatically and regardless of the level of vigilance. In this study use a MMN protocol to
      highlight phonemic discrimination capacities and then link them to subjective performances in
      the adult cochlear implant users. The first objective is to establish in these users a
      concordance between the amplitude of the MMN and a test of discrimination of logatoms, both
      highlighting the capacities of auditory discrimination. The second is to establish a
      concordance between the amplitude of the MMN and the scores obtained with the PBK.

      Method

      A forced choice test will evaluate the discrimination of the most confusing logatoms in the
      cochlear implant users, and representative of the French language. The following couples were
      selected:

        -  " fa " vs " sa "

        -  " la " vs " na "

        -  " pan " vs " pa "

        -  " pa " vs " ta "

        -  " pon " vs " po " Each couple of logatoms will be tested twenty times. If the score is
           greater than 16/20, the discrimination of logatoms pair will be considered positive. The
           test, carried out using Matlab MathWorks software, was automated so that the patient
           could do it without the intervention of the experimenter; It remains under its
           supervision in order to verify that the test is proceeding normally.

      Obtaining the MMN requires a paradigm called "oddball", during which a "frequent" stimulus is
      emitted 80% of the time and a second stimulus called "deviant" is presented only 20% of the
      time. The high repetition rate of the frequent stimulus ("pa" for example) creates an
      electrophysiological baseline. When a deviant stimulus ("ba" for example) appears, this
      introduces a break in the electrophysiological baseline which results in the appearance of a
      so-called mismatch negative wave, the MMN. It shows the discrimination by the auditory system
      of two different stimuli. By studying the amplitude of this wave, it is possible to evaluate
      the quality of discrimination. A low or zero amplitude means that the subject did not
      discriminate the two logatoms. Conversely, the higher the amplitude, the greater the
      discrimination quality is. The wave latency can also be a variable to be observed. The
      earlier it is, the more it marks the ease of discrimination.

      For each subject, the concordance with the score in the logatoms discrimination test will be
      analyzed separately for each pair. This will make it possible to evaluate the consistency of
      this concordance according to the pairs of tested logatoms. The optimal threshold of the MMN
      amplitude to identify subjects with good auditory discrimination is not yet known (innovative
      method). The first stage of our analysis will be to search for this threshold by constructing
      an receiver operating characteristic (ROC) curve to best distinguish patients with good and
      bad auditory discrimination in the test of the logatoms (choice of the threshold by the index
      of Youden). This threshold will then be used to classify subjects as having good or poor
      auditory discrimination according to the EEG. The agreement between the results of the EEG
      and the test of logatoms discrimination will then be analyzed by the calculation of a Kappa
      coefficient.

      The PBK test will be used to evaluate an overall comprehension score. This test consists of 4
      lists of 50 words respecting the occurrence of the phonemes of the French language and using
      mono- and bi-syllabic words. A score above 70% is accepted as a good performance. The
      concordance between the results of the EEG procedure for each logatoms (good and bad auditory
      discrimination defined as above) and the result of the PBK test will be analyzed using Kappa
      coefficients.

      Finally, different secondary data will be collected: type of cochlear implant (mark, internal
      and external part), duration of implantation in months, etiology, data related to the implant
      setting (number of active electrodes , Thresholds C and T, IDR, automatic functions like
      SCAN, ADRO, ...)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Correlation between MMN amplitude and logatoms discrimination score in the discrimination capacity
time frame: 30 days
description: The discrimination capacity (positive/ negative) defined by an MMN amplitude above a threshold will be estimated using a ROC curve based on the logatoms discrimination scores The discrimination capacity defined by logatoms test will be positive if the discrimination score is higher or equal to 80%.
measure: Correlation between MMN amplitude and the Phonetically Balanced Kindergarten score and Vocoder test
time frame: within the first 30 days after the first visit
description: The discrimination capacity will be positive if the correlation score is higher or equal to 70%.
arm group label: Adult cochlear implant users
arm group type: Other
description: Evaluation of a concordance between the mismatch negativity amplitude mesured by electroencephalography and the capacity of logatoms discrimination by using a logatoms test
intervention type: Other
intervention name: logatoms test
description: A forced choice test will evaluate the discrimination of the most confusing logatoms in the cochlear implant users, and representative of the French language.
arm group label: Adult cochlear implant users
intervention type: Other
intervention name: Electroencephalography
description: Mesure of the mismatch negativity wave
arm group label: Adult cochlear implant users
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Frédéric VENAIL, PH
role: Principal Investigator
affiliation: University Hospital, Montpellier
last name: Frédéric VENAIL, PH
phone: 0467336800
phone ext: +33
email: f-venail@chu-montpellier.fr
last name: Antoine LORENZI
email: a-lorenzi@chu-montpellier.fr
facility: 
status: Recruiting
contact: 
contact backup: 
country: France
responsible party type: Sponsor
sharing ipd: No