<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/NCT02224469</url>
  </required_header>
  <id_info>
    <org_study_id>UMCU 12-370</org_study_id>
    <secondary_id>STW 12803</secondary_id>
    <nct_id>NCT02224469</nct_id>
  </id_info>
  <brief_title>First Study With a Brain Implant to Help Locked-in Patients Communicate at Home</brief_title>
  <acronym>UNP</acronym>
  <official_title>Utrecht Neural Prosthesis (UNP): A Pilot Study on Controllability of Brain Signals and Application in locked-in Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UMC Utrecht</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>UMC Utrecht</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study a new means of communication for people with locked-in syndrome will be tested.&#xD;
      The investigators will record brain signals directly from the surface of the brain by means&#xD;
      of a completely implantable system. These brain signals are fed wirelessly into an assistive&#xD;
      technology device and will control this device for communication and environmental control at&#xD;
      the users home.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this pilot study we will provide locked-in people with a new means of communication which&#xD;
      has not been possible up to now. For the first time, we will test whether we can record and&#xD;
      decode neural signals obtained directly from the brain, for control over a computer. The&#xD;
      target population is people with locked-in syndrome. For these patients there is no technique&#xD;
      available to allow them to communicate unaided. We have developed a brain-computer interface&#xD;
      (BCI) system that can read activity directly from the brain, and can convert the activity to&#xD;
      a digital switch. The system, called the Utrecht Neural Prosthesis (UNP), consists of an&#xD;
      implantable amplifier for electrical brain signals, a set of electrodes positioned on the&#xD;
      surface of the brain and a wireless receiver, placed outside of the body. A dedicated&#xD;
      computer will convert the signals to electrical pulses for standard Assistive Technology&#xD;
      devices. The UNP can in principle enable the patient to engage in any activity that is&#xD;
      offered by commercial Assistive Technology companies that can be performed with switch&#xD;
      signals, for instance operating home apparatus or writing text. Most importantly, we aim to&#xD;
      achieve unsupervised function of the BCI, meaning that the patient will be able to use it at&#xD;
      home without the aid of researchers or other experts (but with minimal caregiver assistance).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 21, 2013</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Unsupervised BCI performance</measure>
    <time_frame>up to 1 year</time_frame>
    <description>The system correctly detects a switch brain signal within 10 sec in a real life, cognitively engaging context, such as operating a spelling device. A formal test has been designed, in which the patient has to copy a 30 character sentence within 30 minutes, with a margin of 20% faulty characters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient Satisfaction</measure>
    <time_frame>up to 1 year</time_frame>
    <description>subjective ratings, hours use of BCI system per week, quality of life</description>
  </secondary_outcome>
  <other_outcome>
    <measure>supervised BCI performance</measure>
    <time_frame>up to 28 weeks</time_frame>
    <description>The patient is able to generate switch commands with at least 80 % correct, with the help of a BCI researcher and/or caregiver (using a formal test)</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Locked-In Syndrome</condition>
  <arm_group>
    <arm_group_label>ECoG (electrocorticography) sensing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Use ECoG-based Brain Computer interface to control assistive technology</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>ECoG (electrocorticography) sensing</intervention_name>
    <description>Implant electrodes and sensing device and use for control of Assistive Technology</description>
    <arm_group_label>ECoG (electrocorticography) sensing</arm_group_label>
    <other_name>Activa PC + S</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 - 75&#xD;
&#xD;
          -  Locked-in status (i.e. severely paralyzed with communication problems)&#xD;
&#xD;
               -  in case of trauma or stroke: at least 1 year after the event&#xD;
&#xD;
               -  in case of a neuromuscular disease: slow progression allowed&#xD;
&#xD;
          -  Rudimentary form of communication possible (e.g. through assistive technology, eye&#xD;
             blinks or eye movements, severely impaired speech)&#xD;
&#xD;
          -  Mentally and physically capable of giving informed consent&#xD;
&#xD;
          -  Lives in or close to the Netherlands&#xD;
&#xD;
          -  MR compatible&#xD;
&#xD;
               -  able to lie flat in the scanner&#xD;
&#xD;
               -  no metal objects in or attached to the body&#xD;
&#xD;
               -  no claustrophobia&#xD;
&#xD;
          -  Visus (largely) intact&#xD;
&#xD;
          -  Cognition intact (IQ&gt;80)&#xD;
&#xD;
          -  Compatible with implantation procedure&#xD;
&#xD;
               -  good respiratory function or stable respiratory situation using ventilation&#xD;
                  assistance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Strong and frequent spasms&#xD;
&#xD;
          -  Vital indication for blood thinners&#xD;
&#xD;
          -  Current brain tumor or history of tumor resection&#xD;
&#xD;
          -  Quick medical or neurological deterioration&#xD;
&#xD;
          -  Patients who are considered legally incapable (and who therefore will not be able to&#xD;
             give informed consent)&#xD;
&#xD;
          -  Current or recent psychiatric disorder&#xD;
&#xD;
          -  Catabolic state&#xD;
&#xD;
          -  Allergy to the materials of the implant&#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>Nick F Ramsey, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UMC Utrecht</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Medical Center</name>
      <address>
        <city>Utrecht</city>
        <zip>3584CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <link>
    <url>http://www.neuroprosthesis.eu</url>
    <description>Related Info for laymen</description>
  </link>
  <link>
    <url>http://www.nick-ramsey.eu</url>
    <description>Info on research group</description>
  </link>
  <reference>
    <citation>Vansteensel MJ, Hermes D, Aarnoutse EJ, Bleichner MG, Schalk G, van Rijen PC, Leijten FS, Ramsey NF. Brain-computer interfacing based on cognitive control. Ann Neurol. 2010 Jun;67(6):809-16. doi: 10.1002/ana.21985.</citation>
    <PMID>20517943</PMID>
  </reference>
  <reference>
    <citation>Torres Valderrama A, Paclik P, Vansteensel MJ, Aarnoutse EJ, Ramsey NF. Error probability of intracranial brain computer interfaces under non-task elicited brain states. Clin Neurophysiol. 2012 Dec;123(12):2392-401. doi: 10.1016/j.clinph.2012.05.006. Epub 2012 Jun 12.</citation>
    <PMID>22695047</PMID>
  </reference>
  <results_reference>
    <citation>Vansteensel MJ, Pels EGM, Bleichner MG, Branco MP, Denison T, Freudenburg ZV, Gosselaar P, Leinders S, Ottens TH, Van Den Boom MA, Van Rijen PC, Aarnoutse EJ, Ramsey NF. Fully Implanted Brain-Computer Interface in a Locked-In Patient with ALS. N Engl J Med. 2016 Nov 24;375(21):2060-2066. doi: 10.1056/NEJMoa1608085. Epub 2016 Nov 12.</citation>
    <PMID>27959736</PMID>
  </results_reference>
  <results_reference>
    <citation>Freudenburg ZV, Branco MP, Leinders S, van der Vijgh BH, Pels EGM, Denison T, van den Berg LH, Miller KJ, Aarnoutse EJ, Ramsey NF, Vansteensel MJ. Sensorimotor ECoG Signal Features for BCI Control: A Comparison Between People With Locked-In Syndrome and Able-Bodied Controls. Front Neurosci. 2019 Oct 16;13:1058. doi: 10.3389/fnins.2019.01058. eCollection 2019.</citation>
    <PMID>31680806</PMID>
  </results_reference>
  <results_reference>
    <citation>Pels EGM, Aarnoutse EJ, Leinders S, Freudenburg ZV, Branco MP, van der Vijgh BH, Snijders TJ, Denison T, Vansteensel MJ, Ramsey NF. Stability of a chronic implanted brain-computer interface in late-stage amyotrophic lateral sclerosis. Clin Neurophysiol. 2019 Oct;130(10):1798-1803. doi: 10.1016/j.clinph.2019.07.020. Epub 2019 Jul 27.</citation>
    <PMID>31401488</PMID>
  </results_reference>
  <results_reference>
    <citation>Pels EGM, Aarnoutse EJ, Ramsey NF, Vansteensel MJ. Estimated Prevalence of the Target Population for Brain-Computer Interface Neurotechnology in the Netherlands. Neurorehabil Neural Repair. 2017 Jul;31(7):677-685. doi: 10.1177/1545968317714577. Epub 2017 Jun 22.</citation>
    <PMID>28639486</PMID>
  </results_reference>
  <results_reference>
    <citation>Leinders S, Vansteensel MJ, Branco MP, Freudenburg ZV, Pels EGM, Van der Vijgh B, Van Zandvoort MJE, Ramsey NF, Aarnoutse EJ. Dorsolateral prefrontal cortex-based control with an implanted brain-computer interface. Sci Rep. 2020 Sep 22;10(1):15448. doi: 10.1038/s41598-020-71774-5.</citation>
    <PMID>32963279</PMID>
  </results_reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 21, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 25, 2014</study_first_posted>
  <last_update_submitted>January 20, 2023</last_update_submitted>
  <last_update_submitted_qc>January 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>UMC Utrecht</investigator_affiliation>
    <investigator_full_name>Dr E. J. Aarnoutse</investigator_full_name>
    <investigator_title>Study Coordinator</investigator_title>
  </responsible_party>
  <keyword>Brain-Computer Interface</keyword>
  <keyword>Motor Cortex</keyword>
  <keyword>Dorsolateral Prefrontal Cortex</keyword>
  <keyword>Quality of Life</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Locked-In Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>selected datasets will be available through a public repository after publication of results</ipd_description>
    <ipd_time_frame>From Nov 14, 2016, no end date</ipd_time_frame>
    <ipd_access_criteria>According to http://datadryad.org/pages/policies</ipd_access_criteria>
    <ipd_url>http://datadryad.org/resource/doi:10.5061/dryad.k9f10</ipd_url>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_id>k9f10</doc_id>
      <doc_type>Individual Participant Data Set</doc_type>
      <doc_url>http://datadryad.org/resource/doi:10.5061/dryad.k9f10</doc_url>
    </study_doc>
  </study_docs>
  <!-- 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/NCT02224469
org study id: UMCU 12-370
secondary id: STW 12803
nct id: NCT02224469
lead sponsor: 
has dmc: Yes
In this study a new means of communication for people with locked-in syndrome will be tested.
      The investigators will record brain signals directly from the surface of the brain by means
      of a completely implantable system. These brain signals are fed wirelessly into an assistive
      technology device and will control this device for communication and environmental control at
      the users home.
In this pilot study we will provide locked-in people with a new means of communication which
      has not been possible up to now. For the first time, we will test whether we can record and
      decode neural signals obtained directly from the brain, for control over a computer. The
      target population is people with locked-in syndrome. For these patients there is no technique
      available to allow them to communicate unaided. We have developed a brain-computer interface
      (BCI) system that can read activity directly from the brain, and can convert the activity to
      a digital switch. The system, called the Utrecht Neural Prosthesis (UNP), consists of an
      implantable amplifier for electrical brain signals, a set of electrodes positioned on the
      surface of the brain and a wireless receiver, placed outside of the body. A dedicated
      computer will convert the signals to electrical pulses for standard Assistive Technology
      devices. The UNP can in principle enable the patient to engage in any activity that is
      offered by commercial Assistive Technology companies that can be performed with switch
      signals, for instance operating home apparatus or writing text. Most importantly, we aim to
      achieve unsupervised function of the BCI, meaning that the patient will be able to use it at
      home without the aid of researchers or other experts (but with minimal caregiver assistance).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Unsupervised BCI performance
time frame: up to 1 year
description: The system correctly detects a switch brain signal within 10 sec in a real life, cognitively engaging context, such as operating a spelling device. A formal test has been designed, in which the patient has to copy a 30 character sentence within 30 minutes, with a margin of 20% faulty characters.
measure: Patient Satisfaction
time frame: up to 1 year
description: subjective ratings, hours use of BCI system per week, quality of life
measure: supervised BCI performance
time frame: up to 28 weeks
description: The patient is able to generate switch commands with at least 80 % correct, with the help of a BCI researcher and/or caregiver (using a formal test)
arm group label: ECoG (electrocorticography) sensing
arm group type: Experimental
description: Use ECoG-based Brain Computer interface to control assistive technology
intervention type: Device
intervention name: ECoG (electrocorticography) sensing
description: Implant electrodes and sensing device and use for control of Assistive Technology
arm group label: ECoG (electrocorticography) sensing
other name: Activa PC + S
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Nick F Ramsey, PhD
role: Principal Investigator
affiliation: UMC Utrecht
facility: 
country: Netherlands
url: http://www.neuroprosthesis.eu
description: Related Info for laymen
url: http://www.nick-ramsey.eu
description: Info on research group
citation: Vansteensel MJ, Hermes D, Aarnoutse EJ, Bleichner MG, Schalk G, van Rijen PC, Leijten FS, Ramsey NF. Brain-computer interfacing based on cognitive control. Ann Neurol. 2010 Jun;67(6):809-16. doi: 10.1002/ana.21985.
PMID: 20517943
citation: Torres Valderrama A, Paclik P, Vansteensel MJ, Aarnoutse EJ, Ramsey NF. Error probability of intracranial brain computer interfaces under non-task elicited brain states. Clin Neurophysiol. 2012 Dec;123(12):2392-401. doi: 10.1016/j.clinph.2012.05.006. Epub 2012 Jun 12.
PMID: 22695047
citation: Vansteensel MJ, Pels EGM, Bleichner MG, Branco MP, Denison T, Freudenburg ZV, Gosselaar P, Leinders S, Ottens TH, Van Den Boom MA, Van Rijen PC, Aarnoutse EJ, Ramsey NF. Fully Implanted Brain-Computer Interface in a Locked-In Patient with ALS. N Engl J Med. 2016 Nov 24;375(21):2060-2066. doi: 10.1056/NEJMoa1608085. Epub 2016 Nov 12.
PMID: 27959736
citation: Freudenburg ZV, Branco MP, Leinders S, van der Vijgh BH, Pels EGM, Denison T, van den Berg LH, Miller KJ, Aarnoutse EJ, Ramsey NF, Vansteensel MJ. Sensorimotor ECoG Signal Features for BCI Control: A Comparison Between People With Locked-In Syndrome and Able-Bodied Controls. Front Neurosci. 2019 Oct 16;13:1058. doi: 10.3389/fnins.2019.01058. eCollection 2019.
PMID: 31680806
citation: Pels EGM, Aarnoutse EJ, Leinders S, Freudenburg ZV, Branco MP, van der Vijgh BH, Snijders TJ, Denison T, Vansteensel MJ, Ramsey NF. Stability of a chronic implanted brain-computer interface in late-stage amyotrophic lateral sclerosis. Clin Neurophysiol. 2019 Oct;130(10):1798-1803. doi: 10.1016/j.clinph.2019.07.020. Epub 2019 Jul 27.
PMID: 31401488
citation: Pels EGM, Aarnoutse EJ, Ramsey NF, Vansteensel MJ. Estimated Prevalence of the Target Population for Brain-Computer Interface Neurotechnology in the Netherlands. Neurorehabil Neural Repair. 2017 Jul;31(7):677-685. doi: 10.1177/1545968317714577. Epub 2017 Jun 22.
PMID: 28639486
citation: Leinders S, Vansteensel MJ, Branco MP, Freudenburg ZV, Pels EGM, Van der Vijgh B, Van Zandvoort MJE, Ramsey NF, Aarnoutse EJ. Dorsolateral prefrontal cortex-based control with an implanted brain-computer interface. Sci Rep. 2020 Sep 22;10(1):15448. doi: 10.1038/s41598-020-71774-5.
PMID: 32963279
responsible party type: Principal Investigator
investigator affiliation: UMC Utrecht
investigator full name: Dr E. J. Aarnoutse
investigator title: Study Coordinator
mesh term: Locked-In Syndrome
sharing ipd: Yes
ipd description: selected datasets will be available through a public repository after publication of results
ipd time frame: From Nov 14, 2016, no end date
ipd access criteria: According to http://datadryad.org/pages/policies
ipd url: http://datadryad.org/resource/doi:10.5061/dryad.k9f10
study doc: 