<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/NCT02984202</url>
  </required_header>
  <id_info>
    <org_study_id>NIH U01 DC013030</org_study_id>
    <nct_id>NCT02984202</nct_id>
  </id_info>
  <brief_title>Auditory Midbrain Implant Study</brief_title>
  <official_title>Phase I Safety Study for a New Two-Shank Auditory Midbrain Implant (AMI)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hannover Medical School</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cochlear</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hannover Medical School</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objectives of the clinical study are to implant five deaf patients (those with&#xD;
      Neurofibromatosis Type II, NF2) with a new two-shank auditory midbrain implant array (AMI;&#xD;
      developed by Cochlear Limited) into the central nucleus of the inferior colliculus in order&#xD;
      to assess the safety, reliability, consistency of placement, and performance of the AMI&#xD;
      device. The clinical trial is being performed at Hannover Medical School in Germany in&#xD;
      collaboration with University of Minnesota (USA) and Cochlear Limited (Australia). The&#xD;
      clinical trial is being managed by Hannover Clinical Trial Center in Germany.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cochlear implants are used in the cochlea (part of the inner ear) where they send electrical&#xD;
      signals for activation of the auditory nerve to restore hearing to deaf patients. For&#xD;
      patients without a functioning auditory nerve, there is an auditory brainstem implant (ABI),&#xD;
      which is placed on the surface of the brainstem in a more central location to restore&#xD;
      hearing. Unfortunately, the hearing performance of the ABI is typically lower than the&#xD;
      performance of the cochlear implant. There are several reasons for the lower success of the&#xD;
      ABI. Due to the tumor and/or tumor removal process for the NF2 condition, there is potential&#xD;
      damage caused at the brainstem level that has been linked to the poorer performance. The&#xD;
      anatomical changes caused by the tumor also make it difficult to properly visualize and place&#xD;
      the ABI surface array into the correct location. In addition, if there is a large tumor that&#xD;
      needs to or has been removed, then there can be a large cavity in the brainstem space with&#xD;
      the possibility that the ABI surface array can move from its initial location over time.&#xD;
&#xD;
      Therefore, for the past 16 years, a new implant has been developed in an international&#xD;
      collaboration that presents electrical stimuli into a midbrain region, the inferior&#xD;
      colliculus. This new implant is called the auditory midbrain implant (AMI). The current&#xD;
      version consists of two shanks with with 11 electrode contacts linearly spaced along each&#xD;
      shank. The two shanks are inserted into the inferior colliculus to align the electrodes along&#xD;
      different pitch layers to be able to stimulate them individually with varying temporal pulse&#xD;
      patterns.&#xD;
&#xD;
      In the period from 2006 to 2010, a former version of the current AMI was implanted and&#xD;
      evaluated in five NF2 deaf patients for hearing restoration. This first AMI implant consisted&#xD;
      of only one shank in contrast with the current two-shank array. Encouragingly, the clinical&#xD;
      trial at that time showed that the AMI was safe for all five patients. All patients achieved&#xD;
      improvements in their hearing capacity, especially in the form of environmental sound&#xD;
      awareness and lip-reading enhancement. One patient additionally attained good speech&#xD;
      perception that is within the upper range of ABI NF2 patients. However, this speech&#xD;
      perception is not yet at the level that can be attained in cochlear implant patients.&#xD;
&#xD;
      Based on these experiences and additional studies in animals, we have developed the second&#xD;
      version of the AMI that consists of two shanks that will be implanted into the inferior&#xD;
      colliculus and is expected to provide significant improvements in hearing performance&#xD;
      compared to the previous AMI by stimulating more effectively across the three-dimensional&#xD;
      inferior colliculus.&#xD;
&#xD;
      The purpose of this clinical trial is to evaluate the safety, reliability, and performance of&#xD;
      the new two-shank AMI in deaf NF2 patients. The ability to consistency place the AMI array&#xD;
      into the inferior colliculus will also be evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 17, 2016</start_date>
  <completion_date type="Actual">June 25, 2020</completion_date>
  <primary_completion_date type="Actual">June 25, 2020</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Collection of serious adverse events of AMI</measure>
    <time_frame>24 months</time_frame>
    <description>Collection of investigational device related serious adverse events during the evaluation period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Position of AMI array in midbrain</measure>
    <time_frame>24 months</time_frame>
    <description>Evaluation of the final position of the two shanks of the AMI array in the inferior colliculus which includes angles and insertion locations of each shank relative to specific anatomical landmarks. The frequency/pitch ordering of the sites along each shank will also be measured which provides how many electrode sites are correctly positioned into the inferior colliculus and thus the depth location of each shank relative to the surface of the midbrain. All of these measurements provide the final position of the AMI array in the midbrain.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Speech perception performance of AMI</measure>
    <time_frame>24 months</time_frame>
    <description>Relative difference of the speech perception score between current ABI recipients with NF2 (collected data from the same clinical site) and AMI recipients with NF2 at the two-year post-operative evaluation visit.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Deafness; Perception</condition>
  <arm_group>
    <arm_group_label>Safety/Efficacy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be implanted with the AMI and evaluated for safety and efficacy over a 2-year period. The placement of the AMI array into the inferior colliculus will also be evaluated.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>auditory midbrain implant (AMI)</intervention_name>
    <arm_group_label>Safety/Efficacy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥18 and ≤75 years&#xD;
&#xD;
          2. Diagnosis of NF2 (i.e., Neurofibromatosis Type 2)&#xD;
&#xD;
          3. Bilateral deafness without a functional auditory nerve or insufficient residual&#xD;
             hearing while being ineligible for cochlear implant&#xD;
&#xD;
          4. Eligible for brainstem or midbrain surgery for a standard clinical procedure,&#xD;
             including to remove a tumor, replace or reposition an existing ABI, or implant a new&#xD;
             ABI&#xD;
&#xD;
          5. No or minimal benefit from a previously implanted auditory brainstem implant (ABI)&#xD;
             (i.e. patient has requested an alternative hearing option due to insufficient benefit&#xD;
             on a daily basis); or poor performance expected with an ABI due to a high risk of&#xD;
             array movement associated with removal of a large tumor or anatomical&#xD;
             abnormalities/damage (e.g., associated with altered development, tumor compression,&#xD;
             radiation therapy, surgical intervention, or other treatments)&#xD;
&#xD;
          6. No further lesions of the auditory pathway from the inferior colliculus (IC) to the&#xD;
             auditory cortex&#xD;
&#xD;
          7. Post-linguistic onset of contralateral severe-to-profound neural hearing loss&#xD;
&#xD;
          8. Women with childbearing potential: willingness to use a reliable contraceptive method&#xD;
             (e.g. copper intrauterine devices or hormonal methods) after consulting their&#xD;
             gynecologists&#xD;
&#xD;
          9. Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Medical, neurological, or psychological conditions that would contra-indicate&#xD;
             undergoing surgery, e.g. acute cardiac infarction, history of stroke, dementia&#xD;
&#xD;
          2. Additional handicaps that would prevent participation in evaluations&#xD;
&#xD;
          3. Pregnant and breast feeding woman, prisoners, or anyone in custody&#xD;
&#xD;
          4. Known allergies to one of the components of the implant&#xD;
&#xD;
          5. Other active devices with potential interference with brain implants, such as&#xD;
             transcranial magnetic stimulators&#xD;
&#xD;
          6. Additionally, in the event of other serious diseases (e.g. progressive carcinoma or&#xD;
             chronic renal failure) the investigators will decide on a case-by-case basis whether&#xD;
             to enroll the patient in the trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hannover Medical School</name>
      <address>
        <city>Hannover</city>
        <state>Lower Saxony</state>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>July 31, 2020</last_update_submitted>
  <last_update_submitted_qc>July 31, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Deafness</mesh_term>
    <mesh_term>Hearing Loss, Sensorineural</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/NCT02984202
org study id: NIH U01 DC013030
nct id: NCT02984202
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The objectives of the clinical study are to implant five deaf patients (those with
      Neurofibromatosis Type II, NF2) with a new two-shank auditory midbrain implant array (AMI;
      developed by Cochlear Limited) into the central nucleus of the inferior colliculus in order
      to assess the safety, reliability, consistency of placement, and performance of the AMI
      device. The clinical trial is being performed at Hannover Medical School in Germany in
      collaboration with University of Minnesota (USA) and Cochlear Limited (Australia). The
      clinical trial is being managed by Hannover Clinical Trial Center in Germany.
Cochlear implants are used in the cochlea (part of the inner ear) where they send electrical
      signals for activation of the auditory nerve to restore hearing to deaf patients. For
      patients without a functioning auditory nerve, there is an auditory brainstem implant (ABI),
      which is placed on the surface of the brainstem in a more central location to restore
      hearing. Unfortunately, the hearing performance of the ABI is typically lower than the
      performance of the cochlear implant. There are several reasons for the lower success of the
      ABI. Due to the tumor and/or tumor removal process for the NF2 condition, there is potential
      damage caused at the brainstem level that has been linked to the poorer performance. The
      anatomical changes caused by the tumor also make it difficult to properly visualize and place
      the ABI surface array into the correct location. In addition, if there is a large tumor that
      needs to or has been removed, then there can be a large cavity in the brainstem space with
      the possibility that the ABI surface array can move from its initial location over time.

      Therefore, for the past 16 years, a new implant has been developed in an international
      collaboration that presents electrical stimuli into a midbrain region, the inferior
      colliculus. This new implant is called the auditory midbrain implant (AMI). The current
      version consists of two shanks with with 11 electrode contacts linearly spaced along each
      shank. The two shanks are inserted into the inferior colliculus to align the electrodes along
      different pitch layers to be able to stimulate them individually with varying temporal pulse
      patterns.

      In the period from 2006 to 2010, a former version of the current AMI was implanted and
      evaluated in five NF2 deaf patients for hearing restoration. This first AMI implant consisted
      of only one shank in contrast with the current two-shank array. Encouragingly, the clinical
      trial at that time showed that the AMI was safe for all five patients. All patients achieved
      improvements in their hearing capacity, especially in the form of environmental sound
      awareness and lip-reading enhancement. One patient additionally attained good speech
      perception that is within the upper range of ABI NF2 patients. However, this speech
      perception is not yet at the level that can be attained in cochlear implant patients.

      Based on these experiences and additional studies in animals, we have developed the second
      version of the AMI that consists of two shanks that will be implanted into the inferior
      colliculus and is expected to provide significant improvements in hearing performance
      compared to the previous AMI by stimulating more effectively across the three-dimensional
      inferior colliculus.

      The purpose of this clinical trial is to evaluate the safety, reliability, and performance of
      the new two-shank AMI in deaf NF2 patients. The ability to consistency place the AMI array
      into the inferior colliculus will also be evaluated.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Collection of serious adverse events of AMI
time frame: 24 months
description: Collection of investigational device related serious adverse events during the evaluation period.
measure: Position of AMI array in midbrain
time frame: 24 months
description: Evaluation of the final position of the two shanks of the AMI array in the inferior colliculus which includes angles and insertion locations of each shank relative to specific anatomical landmarks. The frequency/pitch ordering of the sites along each shank will also be measured which provides how many electrode sites are correctly positioned into the inferior colliculus and thus the depth location of each shank relative to the surface of the midbrain. All of these measurements provide the final position of the AMI array in the midbrain.
measure: Speech perception performance of AMI
time frame: 24 months
description: Relative difference of the speech perception score between current ABI recipients with NF2 (collected data from the same clinical site) and AMI recipients with NF2 at the two-year post-operative evaluation visit.
arm group label: Safety/Efficacy
arm group type: Experimental
description: Patients will be implanted with the AMI and evaluated for safety and efficacy over a 2-year period. The placement of the AMI array into the inferior colliculus will also be evaluated.
intervention type: Device
intervention name: auditory midbrain implant (AMI)
arm group label: Safety/Efficacy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Deafness
mesh term: Hearing Loss, Sensorineural