<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/NCT03827187</url>
  </required_header>
  <id_info>
    <org_study_id>136640</org_study_id>
    <nct_id>NCT03827187</nct_id>
  </id_info>
  <brief_title>Awareness Detection and Communication in Disorders of Consciousness</brief_title>
  <official_title>EEG Based Awareness Detection and Communication in Prolonged Disorders of Consciousness and Physical Disability</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Ulster</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Rehabilitation Hospital, Ireland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Belfast Health and Social Care Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Western Health and Social Care Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Southern Health and Social Care Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Northern Health and Social Care Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Barnsley Hospital NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>NHS Lothian</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Walton Centre NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hull University Teaching Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Imperial College Healthcare NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Royal Hospital for Neuro-disability</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>South Warwickshire NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sheffield Teaching Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oxford University Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Castel Froma Neuro Care</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Inspire Neurocare</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Huntercombe Group</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Active Care Group</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Ulster</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>
      STUDY OVERVIEW Brain injury can result in a loss of consciousness or awareness, to varying&#xD;
      degrees. Some injuries are mild and cause relatively minor changes in consciousness. However,&#xD;
      in severe cases a person can be left in a state where they are &quot;awake&quot; but unaware, which is&#xD;
      called unresponsive wakefulness syndrome (UWS, previously known as a vegetative state). Up to&#xD;
      43% of patients with a UWS diagnosis, regain some conscious awareness, and are then&#xD;
      reclassified as minimally conscious after further assessment by clinical experts. Many of&#xD;
      those in the minimally conscious state (MCS) and all with unresponsive wakefulness syndrome&#xD;
      (UWS) are incapable of providing any, or consistent, overt motor responses and therefore, in&#xD;
      some cases, existing measures of consciousness are not able to provide an accurate&#xD;
      assessment. Furthermore, patients with locked-in syndrome (LIS), which is not a disorder of&#xD;
      consciousness as patients are wholly aware, also, struggle to produce overt motor responses&#xD;
      due to paralysis and anarthria, leading to long delays in accurate diagnoses using current&#xD;
      measures to determine levels of consciousness and awareness. There is evidence that LIS&#xD;
      patients, and a subset of patients with prolonged disorders of consciousness (DoC), can&#xD;
      imagine movement (such as imagining lifting a heavy weight with their right arm) when given&#xD;
      instructions presented either auditorily or visually - and the pattern of brain activity that&#xD;
      they produce when imagining these movements, can be recorded using a method known as&#xD;
      electroencephalography (or EEG). With these findings, the investigators have gathered&#xD;
      evidence that EEG-based bedside detection of conscious awareness is possible using Brain-&#xD;
      Computer Interface (BCI) technology - whereby a computer programme translates information&#xD;
      from the users EEG-recorded patterns of activity, to computer commands that allow the user to&#xD;
      interact via a user interface. The BCI system for the current study employs three possible&#xD;
      imagined movement combinations for a two-class movement classification; left- vs right-arm,&#xD;
      right-arm vs feet, and left-arm vs feet. Participants are trained, using real-time feedback&#xD;
      on their performance, to use one of these combinations of imagined movement to respond to&#xD;
      'yes' or 'no' answer questions in the Q&amp;A sessions, by imagining one movement for 'yes' and&#xD;
      the other for 'no'. A single combination of movements is chosen for each participant at the&#xD;
      outset, and this participant-specific combination is used throughout their sessions. The&#xD;
      study comprises three phases. The assessment Phase I (sessions 1-2) is to determine if the&#xD;
      patient can imagine movements and produce detectable modulation in sensorimotor rhythms and&#xD;
      thus is responding to instructions. Phase II (sessions 3-6) involves motor-imagery (MI) -BCI&#xD;
      training with neurofeedback to facilitate learning of brain activity modulation; Phase III&#xD;
      (sessions 7-10) assesses patients' MI-BCI response to closed questions, categorized to assess&#xD;
      biographical, numerical, logical, and situational awareness. The present study augments the&#xD;
      evidence of the efficacy for EEG-based BCI technology as an objective movement-independent&#xD;
      diagnostic tool for the assessment of, and distinction between, PDoC and LIS patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRINCIPLE RESEARCH QUESTIONS The project will address a number key principal research&#xD;
      questions largely based on two phases to the study.&#xD;
&#xD;
      Phase/study 1&#xD;
&#xD;
        1. What percentage of disorder of consciousness patients assessed provide evidence of&#xD;
           awareness using EEG-based BCI technology?&#xD;
&#xD;
        2. How does this differ from their clinical diagnosis/prognosis?&#xD;
&#xD;
        3. Does the EEG-based information complement or augment the clinical assessment and&#xD;
           diagnosis process?&#xD;
&#xD;
        4. Do any of those participants who are diagnosed as being in a vegetative state (or MCS)&#xD;
           show signs of awareness beyond the vegetative state based on the EEG-based detection of&#xD;
           awareness protocol?&#xD;
&#xD;
      Phase/study 2&#xD;
&#xD;
        1. Is it possible to train those participants who show clear signs of awareness, as&#xD;
           indicated by significant brain activation during the initial assessment in study 1, to&#xD;
           produce a more prominent and/or consistent response over a number of training sessions&#xD;
           using BCI based training and feedback protocols?&#xD;
&#xD;
        2. Can a subset of the participants use BCI technology to communicate simple responses to&#xD;
           questions at the end of the study or is there enough evidence to suggest that with&#xD;
           further training over a longer period that the participant may use BCI technology as an&#xD;
           alternative or an exclusive communication channel?&#xD;
&#xD;
        3. Does neurotechnology offer any other therapeutic benefits to patients, for example, a&#xD;
           means of technology interaction that is movement independent and engaging brain areas&#xD;
           otherwise not engaged?&#xD;
&#xD;
      SECONDARY RESEARCH Q UESTIONS&#xD;
&#xD;
        1. Does the technology aid feedback/interpretation on assessment outcomes from consultants?&#xD;
&#xD;
        2. How might the experiment provide an opportunity for training others in the deployment of&#xD;
           the technology in a clinical setting?&#xD;
&#xD;
        3. What types of BCI methods of feedback are best auditory/visual or both, musical or&#xD;
           broadband noise, games or applications etc?&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 8, 2022</start_date>
  <completion_date type="Anticipated">August 2026</completion_date>
  <primary_completion_date type="Anticipated">August 2026</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in performance accuracy of BCI use pre- and post- training</measure>
    <time_frame>~10 sessions of ~1.5 hours</time_frame>
    <description>The main primary outcome measure is BCI performance (e.g., accuracy in % for repeated binary choice selections using the BCI e.g., movement free control of cursor towards one of two targets using EEG-based BCI or accuracy in discriminating different brain responses associated with imagined movement of different limbs.&#xD;
Multiple cross validation will be performed to assess the significance of the difference between a baseline accuracy (pre cue- where accuracy in the response is expected to be around 50% (chance level)) and the peak accuracy (where the accuracy of discriminating event related brain response peaks following the cue).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in ability to use imagined movements to consistently communicate yes-no responses to closed questions over multiple sessions by participant with Prolonged Disorder of Consciousness</measure>
    <time_frame>3-4 sessions of ~1.5 hours</time_frame>
    <description>Accuracy rate when using the BCI system to provide known responses to statements will be used to build evidence to establish that participants could use the technology as an aided communication method. Examples of questions are given below.&#xD;
Yes Questions:&#xD;
Your name is David. You are 25 years old.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Diagnostic utility of BCI data provided through study completion to clinicians</measure>
    <time_frame>2 - 7 weeks. Duration of study which lasts 10 sessions of ~1.5 hours in addition to some time for analysis/reporting of results</time_frame>
    <description>The performance accuracy of the participant in producing consistent cue- induced imagined movements appropriately in timed paradigms will be assessed across sessions, to determine variability and consistency in performance accuracy. The affects of real-time feedback will be looked at, alongside differences in performance accuracy across question subcategories. Performance accuracy per question subcategory will be assessed to evaluate awareness of self versus awareness of environment and understanding of numbers and letters, and logic.&#xD;
Whether this information is in line with the patient's current diagnosis/CRS-R and WHIM scores will be assessed in order to further understand whether the technology can aid feedback/interpretation on assessment outcomes from consultants?</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Wessex Head Injury Matrix and Coma Recovery Scale Scores due to potential therapeutic benefit of engaging in motor imagery</measure>
    <time_frame>~10 sessions of ~1.5 hours</time_frame>
    <description>Is there a benefit to intentionally modulating motor cortex regions in response to a command in a timed paradigm over multiple sessions. In participants with a Prolonged Disorder of Consciousness the scores for The Wessex Head Injury Matrix and Coma-Recovery Scale Revised taken at each session will be looked at to seek out therapeutic benefit. Here therapeutic benefit is defined in terms of changes in state of arousal and awareness of self/environment. Therapeutic benefit may also be assessed via performance given as an accuracy percentage of motor imagery trials successfully completed, and how this changes over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in performance accuracy as a factor of whether feedback was presented as music or broadband noise,</measure>
    <time_frame>~10 sessions of ~1.5hours</time_frame>
    <description>Is there a significant difference in performance as a function of type of feedback participant was receiving - music clips or broadband noise.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in performance accuracy as a results of time of day of research experimentation</measure>
    <time_frame>~10 sessions of ~1.5hours</time_frame>
    <description>Arousability varies with time of day - is this reflected in BCI use performance or do some patients perform more optimally at a particular time? The aim is to perform 5 sessions in the morning and 5 in the afternoon to look at the affects of time of day.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Disorder of Consciousness</condition>
  <condition>Paralysis</condition>
  <condition>Motor Neuron Disease</condition>
  <condition>Stroke</condition>
  <condition>Physical Disability</condition>
  <arm_group>
    <arm_group_label>Motor imagery based Brain computer interfacing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Brief assessment of motor imagery in response to command, auditory feedback training and responding to binary yes-no closed questions through Electroencephalography based Brain-computer interfacing.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Motor imagery based EEG-BCI</intervention_name>
    <description>Information gathered in this study may be useful when considering diagnosis of prolonged disorder of consciousness and successful adoption of device could lead to assistive communication intervention with therapeutic benefits. Participants undergo quick assessment to test ability to engage in task, if successful this implies they are minimally conscious, have some awareness of self and memory intact to remember commands. During training participant undergoes multiple sessions whereby they are conducting two different imagined movements to move a sound across the azimuthal plane in a direction dictated by an auditory cue. Participant will receive auditory feedback on the position of the sound which acts as a reflection of how well the participant is engaged in the task in terms of performance and consistency across trials. The participant will move on to use the imagined movements to answer a series of biographical, situational, basic logic and numbers/letters questions.</description>
    <arm_group_label>Motor imagery based Brain computer interfacing</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Study 1 - Initial assessment/screening&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Disorder of consciousness or low awareness state diagnosis ranging from unclear&#xD;
             diagnosis in low awareness states, vegetative state and minimally conscious diagnosis.&#xD;
             Those with locked in syndrome / completed locked in syndrome resulting from injury or&#xD;
             disease e.g., motor neuron disease who do not have health problems that would preclude&#xD;
             them from participating may be assessed but considered as a separate cohort to those&#xD;
             with low awareness states.&#xD;
&#xD;
          -  acute, post-acute patients where appropriate&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants with brain related diseases or illnesses (e.g., progressive neurological&#xD;
             condition or uncontrolled epilepsy) or suffer from pain (these may adversely affect&#xD;
             the brain data produced) and are deemed to be unsuitable for the trials by clinical&#xD;
             teams.&#xD;
&#xD;
          -  Current consumption of medications that cause excessive fatigue or adversely affect&#xD;
             cognitive functioning&#xD;
&#xD;
          -  Where English is not the individual's first language&#xD;
&#xD;
          -  Participant with excessive uncontrollable arm or head movement or teeth grinding as&#xD;
             EEG signal quality will be degraded significantly.&#xD;
&#xD;
        Study 2 - BCI training&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
        - Those identified in study 1 to have a level of awareness based on observed appropriate&#xD;
        brain activations and/or those who have known awareness but are target groups for movement&#xD;
        independent assistive devices and technologies controlled using a brain-computer interface.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Participants who have shown no active brain responses in study 1 where the difference&#xD;
        between baseline&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Damien Coyle, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Ulster</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Damien Coyle, PhD</last_name>
    <phone>+44 28 7167 5170</phone>
    <email>dh.coyle@ulster.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Naomi du Bois, PhD</last_name>
    <phone>+44 28 7167 5321</phone>
    <email>n.du-bois@ulster.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Rehabilitation Hospital of Ireland</name>
      <address>
        <city>Dublin</city>
        <zip>A96 E2H2</zip>
        <country>Ireland</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dr Valerie Twomey</last_name>
      <email>Valerie.Twomey@nrh.ie</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Castel Froma Neuro Care</name>
      <address>
        <city>Warwick</city>
        <state>Warwickshire</state>
        <zip>CV32 6LL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elizabeth Jackson</last_name>
      <email>elizabeth.jackson@castelfroma.org.uk</email>
    </contact>
    <contact_backup>
      <last_name>Damon Hoad</last_name>
      <email>Damon.Hoad@warwick.ac.uk</email>
    </contact_backup>
    <investigator>
      <last_name>Damon Hoad</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Northern Health and Social Care Trust</name>
      <address>
        <city>Antrim</city>
        <zip>BT41 2RL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jacqueline Pogue</last_name>
      <email>jacqueline.pogue@northerntrust.hscni.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Barnsley Hospital NHS Foundation Trust</name>
      <address>
        <city>Barnsley</city>
        <zip>S75 2EP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Simon Judge, MEng</last_name>
      <email>simon.judge@nhs.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Belfast Health and Social Care Trust</name>
      <address>
        <city>Belfast</city>
        <zip>BT9 7AB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sheena Caldwell, MB BCh FRCP(UK)</last_name>
      <email>sheena.caldwell@belfasttrust.hscni.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Frenchay Brain Injury Rehabilitation Centre</name>
      <address>
        <city>Bristol</city>
        <zip>BS16 2UU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suzanne Moss</last_name>
      <email>Suzanne.Moss@huntercombe.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>NHS Lothian</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH9 2HL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr Alasdair Fitzgerald</last_name>
      <email>alasdair.fitzgerald@nhslothian.scot.nhs.uk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hull University Teaching Hospitals NHS Trust</name>
      <address>
        <city>Hull</city>
        <zip>HU3 2JZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Abayomi Salawu, MBBS, FWACS, FRCSI, PGCME, MSc</last_name>
      <email>abayomi.salawu@nhs.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Walton Centre NHS Foundation Trust</name>
      <address>
        <city>Liverpool</city>
        <zip>L9 7LJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ganesh Bavikatte, MBBS, MD, FRCP(London), FEBPRM</last_name>
      <phone>07816 078 294</phone>
      <phone_ext>+44</phone_ext>
      <email>ganesh.bavikatte@thewaltoncentre.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Ganesh Bavikatte, MBBS, MD, FRCP(London), FEBPRM</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Western Health and Social Care Trust</name>
      <address>
        <city>Londonderry</city>
        <zip>BT47 6SB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr Paul Johnson</last_name>
      <email>paul.johnson@westerntrust.hscni.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Huntercombe Group</name>
      <address>
        <city>London</city>
        <zip>SE10 8AD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Samantha Mcantagart</last_name>
      <email>samantha.mcantagart@huntercombe.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Hospital for Neuro-Disability</name>
      <address>
        <city>London</city>
        <zip>SW15 3SW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lloyd Bradley, MD</last_name>
      <email>lbradley@rhn.org.uk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Imperial College Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <zip>W6 8RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr Paul Bentley</last_name>
      <email>p.bentley@imperial.ac.uk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Oxford University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Oxford</city>
        <zip>OX3 7HE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emma Dodds</last_name>
      <email>Emma.Dodds@ouh.nhs.uk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Southern Health and Social Care Trust</name>
      <address>
        <city>Portadown</city>
        <zip>BT63 5QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr Bernadette Salisbury</last_name>
      <email>Bernadette.Salisbury@southerntrust.hscni.ne</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sheffield Teaching Hospitals NHS Foundation Trust</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2JF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sivaraman Nair, DM, FRCP</last_name>
      <email>siva.nair@nhs.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>South Warwickshire NHS Foundation Trust</name>
      <address>
        <city>Warwick</city>
        <zip>CV34 5BW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr Damon Hoad</last_name>
      <email>Damon.Hoad@swft.nhs.uk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Inspire Neurocare Worcester</name>
      <address>
        <city>Worcester</city>
        <zip>WR2 6AS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Harriet Miller</last_name>
      <email>Worcester.CL@inspireneurocare.co.uk</email>
    </contact>
    <contact_backup>
      <last_name>Damon Hoad</last_name>
      <email>Damon.Hoad@warwick.ac.uk</email>
    </contact_backup>
    <investigator>
      <last_name>Damon Hoad</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Ireland</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>September 5, 2018</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>June 28, 2023</last_update_submitted>
  <last_update_submitted_qc>June 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</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>Paralysis</mesh_term>
    <mesh_term>Consciousness Disorders</mesh_term>
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03827187
org study id: 136640
nct id: NCT03827187
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has dmc: No
is fda regulated drug: No
is fda regulated device: No
STUDY OVERVIEW Brain injury can result in a loss of consciousness or awareness, to varying
      degrees. Some injuries are mild and cause relatively minor changes in consciousness. However,
      in severe cases a person can be left in a state where they are "awake" but unaware, which is
      called unresponsive wakefulness syndrome (UWS, previously known as a vegetative state). Up to
      43% of patients with a UWS diagnosis, regain some conscious awareness, and are then
      reclassified as minimally conscious after further assessment by clinical experts. Many of
      those in the minimally conscious state (MCS) and all with unresponsive wakefulness syndrome
      (UWS) are incapable of providing any, or consistent, overt motor responses and therefore, in
      some cases, existing measures of consciousness are not able to provide an accurate
      assessment. Furthermore, patients with locked-in syndrome (LIS), which is not a disorder of
      consciousness as patients are wholly aware, also, struggle to produce overt motor responses
      due to paralysis and anarthria, leading to long delays in accurate diagnoses using current
      measures to determine levels of consciousness and awareness. There is evidence that LIS
      patients, and a subset of patients with prolonged disorders of consciousness (DoC), can
      imagine movement (such as imagining lifting a heavy weight with their right arm) when given
      instructions presented either auditorily or visually - and the pattern of brain activity that
      they produce when imagining these movements, can be recorded using a method known as
      electroencephalography (or EEG). With these findings, the investigators have gathered
      evidence that EEG-based bedside detection of conscious awareness is possible using Brain-
      Computer Interface (BCI) technology - whereby a computer programme translates information
      from the users EEG-recorded patterns of activity, to computer commands that allow the user to
      interact via a user interface. The BCI system for the current study employs three possible
      imagined movement combinations for a two-class movement classification; left- vs right-arm,
      right-arm vs feet, and left-arm vs feet. Participants are trained, using real-time feedback
      on their performance, to use one of these combinations of imagined movement to respond to
      'yes' or 'no' answer questions in the Q&A sessions, by imagining one movement for 'yes' and
      the other for 'no'. A single combination of movements is chosen for each participant at the
      outset, and this participant-specific combination is used throughout their sessions. The
      study comprises three phases. The assessment Phase I (sessions 1-2) is to determine if the
      patient can imagine movements and produce detectable modulation in sensorimotor rhythms and
      thus is responding to instructions. Phase II (sessions 3-6) involves motor-imagery (MI) -BCI
      training with neurofeedback to facilitate learning of brain activity modulation; Phase III
      (sessions 7-10) assesses patients' MI-BCI response to closed questions, categorized to assess
      biographical, numerical, logical, and situational awareness. The present study augments the
      evidence of the efficacy for EEG-based BCI technology as an objective movement-independent
      diagnostic tool for the assessment of, and distinction between, PDoC and LIS patients.
PRINCIPLE RESEARCH QUESTIONS The project will address a number key principal research
      questions largely based on two phases to the study.

      Phase/study 1

        1. What percentage of disorder of consciousness patients assessed provide evidence of
           awareness using EEG-based BCI technology?

        2. How does this differ from their clinical diagnosis/prognosis?

        3. Does the EEG-based information complement or augment the clinical assessment and
           diagnosis process?

        4. Do any of those participants who are diagnosed as being in a vegetative state (or MCS)
           show signs of awareness beyond the vegetative state based on the EEG-based detection of
           awareness protocol?

      Phase/study 2

        1. Is it possible to train those participants who show clear signs of awareness, as
           indicated by significant brain activation during the initial assessment in study 1, to
           produce a more prominent and/or consistent response over a number of training sessions
           using BCI based training and feedback protocols?

        2. Can a subset of the participants use BCI technology to communicate simple responses to
           questions at the end of the study or is there enough evidence to suggest that with
           further training over a longer period that the participant may use BCI technology as an
           alternative or an exclusive communication channel?

        3. Does neurotechnology offer any other therapeutic benefits to patients, for example, a
           means of technology interaction that is movement independent and engaging brain areas
           otherwise not engaged?

      SECONDARY RESEARCH Q UESTIONS

        1. Does the technology aid feedback/interpretation on assessment outcomes from consultants?

        2. How might the experiment provide an opportunity for training others in the deployment of
           the technology in a clinical setting?

        3. What types of BCI methods of feedback are best auditory/visual or both, musical or
           broadband noise, games or applications etc?
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in performance accuracy of BCI use pre- and post- training
time frame: ~10 sessions of ~1.5 hours
description: The main primary outcome measure is BCI performance (e.g., accuracy in % for repeated binary choice selections using the BCI e.g., movement free control of cursor towards one of two targets using EEG-based BCI or accuracy in discriminating different brain responses associated with imagined movement of different limbs.
Multiple cross validation will be performed to assess the significance of the difference between a baseline accuracy (pre cue- where accuracy in the response is expected to be around 50% (chance level)) and the peak accuracy (where the accuracy of discriminating event related brain response peaks following the cue).
measure: Change in ability to use imagined movements to consistently communicate yes-no responses to closed questions over multiple sessions by participant with Prolonged Disorder of Consciousness
time frame: 3-4 sessions of ~1.5 hours
description: Accuracy rate when using the BCI system to provide known responses to statements will be used to build evidence to establish that participants could use the technology as an aided communication method. Examples of questions are given below.
Yes Questions:
Your name is David. You are 25 years old.
measure: Diagnostic utility of BCI data provided through study completion to clinicians
time frame: 2 - 7 weeks. Duration of study which lasts 10 sessions of ~1.5 hours in addition to some time for analysis/reporting of results
description: The performance accuracy of the participant in producing consistent cue- induced imagined movements appropriately in timed paradigms will be assessed across sessions, to determine variability and consistency in performance accuracy. The affects of real-time feedback will be looked at, alongside differences in performance accuracy across question subcategories. Performance accuracy per question subcategory will be assessed to evaluate awareness of self versus awareness of environment and understanding of numbers and letters, and logic.
Whether this information is in line with the patient's current diagnosis/CRS-R and WHIM scores will be assessed in order to further understand whether the technology can aid feedback/interpretation on assessment outcomes from consultants?
measure: Changes in Wessex Head Injury Matrix and Coma Recovery Scale Scores due to potential therapeutic benefit of engaging in motor imagery
time frame: ~10 sessions of ~1.5 hours
description: Is there a benefit to intentionally modulating motor cortex regions in response to a command in a timed paradigm over multiple sessions. In participants with a Prolonged Disorder of Consciousness the scores for The Wessex Head Injury Matrix and Coma-Recovery Scale Revised taken at each session will be looked at to seek out therapeutic benefit. Here therapeutic benefit is defined in terms of changes in state of arousal and awareness of self/environment. Therapeutic benefit may also be assessed via performance given as an accuracy percentage of motor imagery trials successfully completed, and how this changes over time.
measure: Change in performance accuracy as a factor of whether feedback was presented as music or broadband noise,
time frame: ~10 sessions of ~1.5hours
description: Is there a significant difference in performance as a function of type of feedback participant was receiving - music clips or broadband noise.
measure: Changes in performance accuracy as a results of time of day of research experimentation
time frame: ~10 sessions of ~1.5hours
description: Arousability varies with time of day - is this reflected in BCI use performance or do some patients perform more optimally at a particular time? The aim is to perform 5 sessions in the morning and 5 in the afternoon to look at the affects of time of day.
arm group label: Motor imagery based Brain computer interfacing
arm group type: Experimental
description: Brief assessment of motor imagery in response to command, auditory feedback training and responding to binary yes-no closed questions through Electroencephalography based Brain-computer interfacing.
intervention type: Other
intervention name: Motor imagery based EEG-BCI
description: Information gathered in this study may be useful when considering diagnosis of prolonged disorder of consciousness and successful adoption of device could lead to assistive communication intervention with therapeutic benefits. Participants undergo quick assessment to test ability to engage in task, if successful this implies they are minimally conscious, have some awareness of self and memory intact to remember commands. During training participant undergoes multiple sessions whereby they are conducting two different imagined movements to move a sound across the azimuthal plane in a direction dictated by an auditory cue. Participant will receive auditory feedback on the position of the sound which acts as a reflection of how well the participant is engaged in the task in terms of performance and consistency across trials. The participant will move on to use the imagined movements to answer a series of biographical, situational, basic logic and numbers/letters questions.
arm group label: Motor imagery based Brain computer interfacing
criteria: 
gender: All
minimum age: 10 Years
maximum age: 80 Years
healthy volunteers: No
last name: Damien Coyle, PhD
role: Principal Investigator
affiliation: University of Ulster
last name: Damien Coyle, PhD
phone: +44 28 7167 5170
email: dh.coyle@ulster.ac.uk
last name: Naomi du Bois, PhD
phone: +44 28 7167 5321
email: n.du-bois@ulster.ac.uk
facility: 
status: Not yet recruiting
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status: Recruiting
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country: Ireland
country: United Kingdom
responsible party type: Sponsor
mesh term: Paralysis
mesh term: Consciousness Disorders
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
sharing ipd: Undecided