<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/NCT03032497</url>
  </required_header>
  <id_info>
    <org_study_id>2016/00516</org_study_id>
    <secondary_id>RRG1/16013</secondary_id>
    <nct_id>NCT03032497</nct_id>
  </id_info>
  <brief_title>Brain-Computer Interface (BCI)-Based Feedback for Chronic Pain Management</brief_title>
  <official_title>Feasibility of a Brain-Computer Interface (BCI)-Based Adaptive Sensing and Feedback for Chronic Pain Management</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tan Tock Seng Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institute for Infocomm Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Tan Tock Seng Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The feasibility study proposed here will primarily examine the sensitivity of an&#xD;
      electroencephalogram (EEG)-based Brain Computer Interface (BCI) in detecting significant&#xD;
      differences in brain signals in patients with chronic low back pain (N=10), lower limb pain&#xD;
      (N=10) and healthy controls (N=10) through perceived movements via a video and during actual&#xD;
      movements. The BCI device has been approved for use in previous trials (e.g. NNI-IRB/07/001,&#xD;
      DSRB Domain D/09/608, DSRB Domain D/10/072) and the safety and effectiveness of this&#xD;
      non-invasive EEG-based BCI device validated through these trials. However, the validation has&#xD;
      not been specific to its use in pain. Related to the primary objective of the study, we will&#xD;
      develop and validate an adaptive and participant-specific pain detection and analysis program&#xD;
      by exploring and identifying discriminative and robust patterns in spontaneous EEG from our&#xD;
      study sample.&#xD;
&#xD;
      For the secondary objective, we will develop and validate a BCI and computer based pain and&#xD;
      attention diversion training system with interactive audio-visual feedbacks for Phase 2 of&#xD;
      the study. These feedbacks will inform the user about the current brain activation level and&#xD;
      attention level, and guide the user in learning to modulate the EEG characteristics and&#xD;
      develop skills to manage attention to alleviate perceived fear-related pains. The BCI system&#xD;
      captures EEG signals and decodes the underlying brain states in relation to cognition and&#xD;
      fear-related pain perception. Such decoded brain states are then presented to the participant&#xD;
      in visual or other form to guide the participant to learn to regulate the brain states&#xD;
      towards better pain management. For example, the participant may over a few sessions learn to&#xD;
      focus on the visual feedback while inhibiting the brain function activity in relation to&#xD;
      fear-related pain perception. With practice, the user is encouraged to achieve brain activity&#xD;
      modulation without external feedback so fear-related pain can be reduced in realistic&#xD;
      situations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We hypothesize that, using appropriately designed system learning and computing techniques, a&#xD;
      brain-computer interface (BCI) technology can detect specific brain wave patterns in patients&#xD;
      with chronic low back pain or lower limb pain compared to healthy controls. Also, that BCI&#xD;
      technology can detect specific brain wave patterns for fear avoidance behaviours in motor&#xD;
      activities known to trigger pain in such chronic pain patients.&#xD;
&#xD;
      This is a validation and feasibility study. We calculated sufficient funding to cover 10&#xD;
      participants each with low back pain, lower limb pain, healthy controls and BCI training&#xD;
      respectively. Participants will be screened and undergo a comprehensive assessment by the&#xD;
      Rehabilitation Physician (RP) on the study team. The aim of the comprehensive assessment is&#xD;
      to establish the safety and suitability of participants to be study subjects according to&#xD;
      inclusion and exclusion criteria.To ensure a high level of compliance given the high&#xD;
      frequency of visits of the subject during the study, it is important that motivated&#xD;
      volunteers are chosen.&#xD;
&#xD;
      Consent will be taken in an outpatient consultation room at the pain management clinic(PMC)&#xD;
      at Tan Tock Seng Hospital, with full provision for privacy. PMC is where the study will be&#xD;
      conducted. Informed consent will be taken at the convenience of the potential participant. A&#xD;
      full explanation of the participant information sheet will be given and any questions&#xD;
      answered.&#xD;
&#xD;
      The study is conducted over 3 phases. Total span of study participation: 11-months.&#xD;
&#xD;
      Phase 1: A total of 2 visits to the study site over 2 consecutive weeks is required. Each&#xD;
      visit will take approximately 1 hour 15 minutes. The 1st session involves a visit to the&#xD;
      doctor's office for a screening assessment-history taking, physical examination, and&#xD;
      electronic notes review no different from the current standard pain consultation. Those found&#xD;
      to be suitable and decide to take part, will be asked at the 2nd session to:&#xD;
&#xD;
        1. Complete a digital set of self-report measures and a 6-minute walking test. These&#xD;
           measures are completed at the start and end of the second session. The walking test will&#xD;
           be conducted by a trained physiotherapist familiar with this measure.&#xD;
&#xD;
        2. Participants then participate in two sets of non-invasive experiments one after another.&#xD;
           The BCI system set-up comprising of a laptop connected to a brain signal recorder and a&#xD;
           headset to record brain signals will be used. Sensors to measure sweat and pulse rate&#xD;
           will also be used in the experiments. The brain signal recorder together with the&#xD;
           sensors will be secured in a backpack and worn by participants during the experiments.&#xD;
&#xD;
      Exp 1-participants watch 15 videos of people doing daily activities. Each video frame is&#xD;
      approximately 1 min long. EEG signal patterns are recorded for each video frame.&#xD;
&#xD;
      Exp 2-participants go through a series of 15 physical movements as guided by the&#xD;
      physiotherapist. Participants are required to complete 15 repetitions each, within 1 min. EEG&#xD;
      signal patterns are recorded for each movement. Two buzzers (labelled &quot;lesser pain&quot; and &quot;more&#xD;
      pain&quot;) are available for participants to press accordingly should they experience 'lesser' or&#xD;
      'more' pain at any point during the experiment. If 'more' pain is experienced, the&#xD;
      physiotherapist will assess the participant's condition and the participant will have a&#xD;
      choice to either (1) continue the experiment at a lower intensity or (2) stop the experiment.&#xD;
&#xD;
      Phase 2: Approximately 6 months after participants' participation in Phase 1 and span a&#xD;
      period of 7 weeks. If selected to complete Phase 2, participants will undergo 18 sessions (3&#xD;
      sessions/week) of brain training over a period of 6 consecutive weeks. Sessions are conducted&#xD;
      on alternate days in the week with each session lasting approximately 1 hour. The same system&#xD;
      set-up used in Phase 1 is used in each training session.&#xD;
&#xD;
      At the start of the first session in week 1, and immediately after completing the last&#xD;
      training session in Week 6 participants will also complete the same set of self-report&#xD;
      questionnaires and the 6-minute walking test (as assessed in Phase 1). At week 7 (1 week post&#xD;
      training) participants will complete the same full set of measures as set out in the second&#xD;
      session of Phase 1.&#xD;
&#xD;
      Phase 3: A total of 2 visits to the study site is required. Each visit will take&#xD;
      approximately 1 hour 15 minutes. These 2 visits will be scheduled approximately 8.5 mths and&#xD;
      10.5 mths after completing Phase 1. Both visit sessions involve a repeat of the full set of&#xD;
      measures that participants completed at the 2nd session in Phase 1.&#xD;
&#xD;
      Potential Risks&#xD;
&#xD;
        1. The potential risks to participants are minimal as none of the measures and components&#xD;
           of the system are invasive. There are currently no known safety issues with the headset&#xD;
           and sensors. However participants will be kept informed of any new findings.&#xD;
&#xD;
        2. Participants may experience temporary exertion related discomfort in the main muscle&#xD;
           groups that are used in the physiotherapy guided movement experiment (Experiment 2)&#xD;
           although the were designed to fit within participants' abilities. Participants will be&#xD;
           advised to contact the Principal Investigator (PI) should the muscular discomfort&#xD;
           persist for more than 24 hours.&#xD;
&#xD;
        3. If participants are screened positive for depression at any point on the study, the PI&#xD;
           who is a trained psychologist will screen them for active depression and where&#xD;
           appropriate refer to the RP for further treatment recommendations. In this case, the&#xD;
           participant will be excluded or withdrawn from the study.&#xD;
&#xD;
        4. Due to the potential of the videos and the guided movements to elicit fear of pain,&#xD;
           participants may experience some increase in anxiety and slight worsening of usual&#xD;
           pains. Experiment 2 is performed under close supervision of the physiotherapist to&#xD;
           prevent any possible strain caused by incorrect movements. If participants experience&#xD;
           'more' pain, the physiotherapist will assess their condition and participants will have&#xD;
           a choice to either (1) continue the experiment at a lower intensity or (2) stop the&#xD;
           experiment.&#xD;
&#xD;
           In the event that participants experience anxiety from participating on any of the&#xD;
           experiments, the PI will assess their symptoms of anxiety and be able to administer&#xD;
           appropriate intervention onsite as necessary at no cost. If further treatment is&#xD;
           required, participants stop the experiment, get re-assessed by the RP and appropriate&#xD;
           referrals will be made for treatment follow-up.&#xD;
&#xD;
        5. As no other medication except simple analgesics such as Paracetamol,&#xD;
           Paracetamol/Orphenadrine, Non-steroidal anti-inflammatory drugs or Tramadol to treat&#xD;
           pain can be taken while participating on the study, there is a possibility pain may be&#xD;
           exacerbated and their condition may worsen. If this occurs, the RP will re-assess their&#xD;
           condition and make appropriate treatment recommendations.&#xD;
&#xD;
        6. If participants pain condition is exacerbated at any point during the course of the&#xD;
           study for reasons not indicated in points 1-4 above, they will be referred to the RP on&#xD;
           the study team for an assessment who will then make appropriate treatment&#xD;
           recommendations.&#xD;
&#xD;
        7. if participants develop significant symptoms because of study participation which&#xD;
           warrants medical intervention, a subsidized medical consult and follow-up treatment will&#xD;
           be at their own costs. The RP on the study team will facilitate a fast tracked&#xD;
           appointment at PMC within 2 weeks.&#xD;
&#xD;
           Study Withdrawal: (a) Participants may withdraw voluntarily from participation in the&#xD;
           study at any time. Participants may also withdraw voluntarily from receiving the study&#xD;
           intervention for any reason. If voluntary withdrawal occurs, the participant will not be&#xD;
           asked to continue scheduled evaluations and their involvement in the study will cease.&#xD;
&#xD;
           (b) Any participant will be withdrawn from further participation on the study if a&#xD;
           serious adverse event classified as having a reasonable causal relationship to the study&#xD;
           occurs. In this case the participant will be given appropriate medical care until the&#xD;
           symptoms resolve or the condition becomes stable. The participant will not be asked to&#xD;
           continue scheduled evaluations and their involvement in the study will cease.&#xD;
&#xD;
           (c) All participants will be withdrawn if there is study closure due to Domain Specific&#xD;
           Review Board (DSRB) review. Participants who drop out of the study will not be replaced.&#xD;
&#xD;
           (d) Any participant can be withdrawn from further participation on the study if the&#xD;
           study team deem it is the best interest of the participant. This can also happen when&#xD;
           the participant does not follow instructions required to complete the study adequately,&#xD;
           or develops other medical problems during the study period.&#xD;
&#xD;
           Specific Restrictions / Requirements:&#xD;
&#xD;
           (a) Standard over the counter pregnancy testing kits will be used for the purposes of&#xD;
           determining if a female of childbearing age is pregnant. (b) All forms of contraception&#xD;
           are allowed during the entire duration of the study (c) Participants are limited to only&#xD;
           taking simple analgesics such as Paracetamol, Paracetamol/Orphenadrine, Non-steroidal&#xD;
           anti-inflammatory drugs (NSAIDs) or Tramadol while participating in the study (d) All&#xD;
           medications (prescription and over the counter), vitamin and mineral supplements, and /&#xD;
           or herbs taken by the participant will be documented.&#xD;
&#xD;
           Data analysis: Self-report outcome measures and data from the walking test will be&#xD;
           analysed via the Statistical Package for the Social Sciences (SPSS) package utilizing&#xD;
           t-tests to measure group differences and pearson bivariate correlations to measure&#xD;
           potential relationships between outcome measures and responses made on Exp 1 (video&#xD;
           condition) and Exp 2 (physiotherapy guided movement condition). EEG patterns will be&#xD;
           analysed via feature analysis in association with clinical signals and user&#xD;
           states/condition including physiological measures of skin conductance and pulse rate.&#xD;
&#xD;
           Data Storage: 1. All hardcopy data, will be stored in designated locked cabinet(s) that&#xD;
           are accessible to authorized study personnel only. 2. All electronic data, they will be&#xD;
           stored on in a secured computer that is password-protected. The databases will not&#xD;
           contain participant identifiers and the data linking participant identifiers and the&#xD;
           participant identification codes will be stored separately including those using&#xD;
           portable media (e.g. CD, USB drives etc.).&#xD;
&#xD;
           Data Access: 1. All study team members will have access to the research data which has&#xD;
           password protection. 2. Data will not be released and shared with individuals or&#xD;
           entities outside the institution. 3. Data will be destroyed after it has been stored for&#xD;
           6 years or minimum duration of retention period as specific by our institutional policy,&#xD;
           whichever that is longer.&#xD;
&#xD;
           Data Monitoring: 1. Safety data will be monitored at every visit with participants asked&#xD;
           to report adverse events since the last visit. 2.There are no anticipated adverse events&#xD;
           or complications expected. However reported adverse events if any, will be fully&#xD;
           recorded, graded in terms of severity, and classified as either not related to the&#xD;
           study, or having a reasonable causal relationship to the study. 3. The PI will be&#xD;
           responsible for reporting all adverse events to DSRB. If excess risk to the&#xD;
           participant/s is observed, or a statistically significant benefit is observed, the study&#xD;
           is stopped early and the patient informed of the results. Futility is not used as a&#xD;
           stopping criteria as this is a feasibility trial design of which there is limited data,&#xD;
           and of a small sample size. The final study results are needed to proof the study&#xD;
           concept here. 4. The PI will be responsible for the dissemination of any data and safety&#xD;
           information to the study site. Communication will be conducted weekly via secure e-mail&#xD;
           to the study team during active phase of the study in Phase 1, 2 and 3. A monthly&#xD;
           face-to-face meetings and where necessary ad hoc meetings during the period of the&#xD;
           study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 5, 2017</start_date>
  <completion_date type="Actual">March 31, 2019</completion_date>
  <primary_completion_date type="Actual">March 31, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assessing change in Numerical pain rating scale</measure>
    <time_frame>Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9</time_frame>
    <description>Measure of pain intensity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessing change in Tampa Kinesiophobia Scale (Miller et al., 1991)</measure>
    <time_frame>Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9</time_frame>
    <description>Measure of fear-avoidance</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessing change in Photograph series of daily activities (PHODA-SeV) scale (Leeuw et al., 2007)</measure>
    <time_frame>Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9</time_frame>
    <description>Measure of patients' perceptions about the consequences of harmful situations based on a series of photographs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessing change in Pain Interference Scale on the Brief Pain Inventory (BPI) (Cleeland &amp; Ryan, 1994)</measure>
    <time_frame>Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9</time_frame>
    <description>Measure of pain interference on daily activities</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessing change in Short-form 36 questionnaire (SF-36) (Ware &amp; Sherbourne, 1992)</measure>
    <time_frame>Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9</time_frame>
    <description>Measure of quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessing change in Patient Health Questionnaire-9 (PHQ-9) (Spitzer et al., 1999)</measure>
    <time_frame>Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9</time_frame>
    <description>Measure of Depressive Symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessing change in Pain Catastrophizing Scale (PCS) (Sullivan et al., 1995)</measure>
    <time_frame>Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9</time_frame>
    <description>Measure of pain related catastrophizing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessing change in 6 minute Shuttle Walk Test</measure>
    <time_frame>Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9</time_frame>
    <description>Objective measure of disability</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Pain, Chronic</condition>
  <arm_group>
    <arm_group_label>EEG-based BCI analysis of fear avoidance</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants complete two experiments one after another-EEG patterns, skin conductance and pulse rate are recorded. The EEG cap is mounted on the participant's head, the GSR sensor secured on the fingers and the PPG sensor secured on the wrist using a Velcro strap. Exp 1-participants watch a series of 15, 1 min videos of people doing daily activities. Exp 2-participants do 15 movements (15 reps each in 1 min) as guided by a physiotherapist. 2 identical buzzers (labelled &quot;lesser pain&quot; and &quot;more pain&quot;) are available to press accordingly should participants experience 'lesser' or 'more' pain any time during the experiment. If 'more' pain experienced, participants' condition will be assessed and they can choose to continue the experiment at a lower intensity or stop.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>EEG-based BCI analysis of fear avoidance</intervention_name>
    <description>Scalp EEG signals that are acquired and recorded from experiment 1 and 2 are analysed for healthy controls, participants with low back pain and participants with lower limb pain. Comparisons of signal patterns are made between groups. Assuming unique signal patterns are obtained for each groups, these signals are further analysed and used to develop a feedback brain training system to better manage pain and ideally reduce fear-avoidant behaviors towards pain.</description>
    <arm_group_label>EEG-based BCI analysis of fear avoidance</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Only English speaking participants are recruited.&#xD;
&#xD;
          -  Participants who are healthy controls need to meet the following inclusion criteria:&#xD;
&#xD;
               1. Not suffering from any active pain condition&#xD;
&#xD;
               2. Without any known disease&#xD;
&#xD;
               3. Not on any long- term medication or health supplements AND&#xD;
&#xD;
               4. Able to complete a digital self-report questionnaire in English without need for&#xD;
                  translation.&#xD;
&#xD;
        Participants who have either low back pain or lower limb pain need to meet the following&#xD;
        inclusion criteria:&#xD;
&#xD;
          1. Diagnosed to have musculoskeletal low back pain OR lower limb pain lasting for &gt; 3&#xD;
             months.&#xD;
&#xD;
          2. Not currently on any active therapy (Example: physiotherapy, stabilisation exercise&#xD;
             therapy) or medication EXCEPT simple analgesics (Paracetamol,&#xD;
             Paracetamol/Orphenadrine, Non-steriodal anti-inflammatory drugs (NSAIDs), Tramadol).&#xD;
&#xD;
          3. Able to complete a digital self-report questionnaire without need for translation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants are excluded from the study if they meet any of the following criteria:&#xD;
&#xD;
               1. Pregnant or lactating.&#xD;
&#xD;
               2. History of drug or alcohol abuse&#xD;
&#xD;
               3. History of significant moderate to severe systemic disease including a confirmed&#xD;
                  diagnosis or current investigation for neoplasm, immunological condition&#xD;
                  involving musculo-skeletal system; active liver, heart and or renal failure;&#xD;
                  respiratory diseases needing supplementary oxygen or Bilevel Positive Airway&#xD;
                  Pressure (BiPAP) machine and any other conditions that make it improbable to&#xD;
                  engage in physical movements.&#xD;
&#xD;
               4. History of psychiatric condition- in particular a psychiatric diagnosis meeting&#xD;
                  Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) criteria for&#xD;
                  major depression, anxiety, phobias or any other conditions that make it&#xD;
                  improbable to engage in physical movements.&#xD;
&#xD;
               5. History of back surgery and surgery involving the joints and bones of the lower&#xD;
                  limbs, such as knee and hip replacement surgery.&#xD;
&#xD;
               6. Spine or lower limb pain that has not been medically stabilised.&#xD;
&#xD;
               7. History of previous injuries to the head and/or brain, including but not limited&#xD;
                  to epilepsy, skull defects or cranioplasty&#xD;
&#xD;
               8. Ongoing compensation claims or litigation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Su-Yin Yang, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tan Tock Seng Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tan Tock Seng Hospital, Pain Management Clinic</name>
      <address>
        <city>Singapore</city>
        <zip>308433</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>Jensen MP, Sherlin LH, Fregni F, Gianas A, Howe JD, Hakimian S. Baseline brain activity predicts response to neuromodulatory pain treatment. Pain Med. 2014 Dec;15(12):2055-63. doi: 10.1111/pme.12546. Epub 2014 Oct 7.</citation>
    <PMID>25287554</PMID>
  </reference>
  <reference>
    <citation>Jensen MP, Hakimian S, Sherlin LH, Fregni F. New insights into neuromodulatory approaches for the treatment of pain. J Pain. 2008 Mar;9(3):193-9. doi: 10.1016/j.jpain.2007.11.003. Epub 2007 Dec 21.</citation>
    <PMID>18096437</PMID>
  </reference>
  <reference>
    <citation>Pinheiro ES, de Queiros FC, Montoya P, Santos CL, do Nascimento MA, Ito CH, Silva M, Nunes Santos DB, Benevides S, Miranda JG, Sa KN, Baptista AF. Electroencephalographic Patterns in Chronic Pain: A Systematic Review of the Literature. PLoS One. 2016 Feb 25;11(2):e0149085. doi: 10.1371/journal.pone.0149085. eCollection 2016.</citation>
    <PMID>26914356</PMID>
  </reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>September 12, 2019</last_update_submitted>
  <last_update_submitted_qc>September 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Brain Computer Interface</keyword>
  <keyword>Electroencephalogram (EEG)</keyword>
  <keyword>Chronic Pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chronic Pain</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is no plan to make IPD available to other researchers.</ipd_description>
  </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/NCT03032497
org study id: 2016/00516
secondary id: RRG1/16013
nct id: NCT03032497
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The feasibility study proposed here will primarily examine the sensitivity of an
      electroencephalogram (EEG)-based Brain Computer Interface (BCI) in detecting significant
      differences in brain signals in patients with chronic low back pain (N=10), lower limb pain
      (N=10) and healthy controls (N=10) through perceived movements via a video and during actual
      movements. The BCI device has been approved for use in previous trials (e.g. NNI-IRB/07/001,
      DSRB Domain D/09/608, DSRB Domain D/10/072) and the safety and effectiveness of this
      non-invasive EEG-based BCI device validated through these trials. However, the validation has
      not been specific to its use in pain. Related to the primary objective of the study, we will
      develop and validate an adaptive and participant-specific pain detection and analysis program
      by exploring and identifying discriminative and robust patterns in spontaneous EEG from our
      study sample.

      For the secondary objective, we will develop and validate a BCI and computer based pain and
      attention diversion training system with interactive audio-visual feedbacks for Phase 2 of
      the study. These feedbacks will inform the user about the current brain activation level and
      attention level, and guide the user in learning to modulate the EEG characteristics and
      develop skills to manage attention to alleviate perceived fear-related pains. The BCI system
      captures EEG signals and decodes the underlying brain states in relation to cognition and
      fear-related pain perception. Such decoded brain states are then presented to the participant
      in visual or other form to guide the participant to learn to regulate the brain states
      towards better pain management. For example, the participant may over a few sessions learn to
      focus on the visual feedback while inhibiting the brain function activity in relation to
      fear-related pain perception. With practice, the user is encouraged to achieve brain activity
      modulation without external feedback so fear-related pain can be reduced in realistic
      situations.
We hypothesize that, using appropriately designed system learning and computing techniques, a
      brain-computer interface (BCI) technology can detect specific brain wave patterns in patients
      with chronic low back pain or lower limb pain compared to healthy controls. Also, that BCI
      technology can detect specific brain wave patterns for fear avoidance behaviours in motor
      activities known to trigger pain in such chronic pain patients.

      This is a validation and feasibility study. We calculated sufficient funding to cover 10
      participants each with low back pain, lower limb pain, healthy controls and BCI training
      respectively. Participants will be screened and undergo a comprehensive assessment by the
      Rehabilitation Physician (RP) on the study team. The aim of the comprehensive assessment is
      to establish the safety and suitability of participants to be study subjects according to
      inclusion and exclusion criteria.To ensure a high level of compliance given the high
      frequency of visits of the subject during the study, it is important that motivated
      volunteers are chosen.

      Consent will be taken in an outpatient consultation room at the pain management clinic(PMC)
      at Tan Tock Seng Hospital, with full provision for privacy. PMC is where the study will be
      conducted. Informed consent will be taken at the convenience of the potential participant. A
      full explanation of the participant information sheet will be given and any questions
      answered.

      The study is conducted over 3 phases. Total span of study participation: 11-months.

      Phase 1: A total of 2 visits to the study site over 2 consecutive weeks is required. Each
      visit will take approximately 1 hour 15 minutes. The 1st session involves a visit to the
      doctor's office for a screening assessment-history taking, physical examination, and
      electronic notes review no different from the current standard pain consultation. Those found
      to be suitable and decide to take part, will be asked at the 2nd session to:

        1. Complete a digital set of self-report measures and a 6-minute walking test. These
           measures are completed at the start and end of the second session. The walking test will
           be conducted by a trained physiotherapist familiar with this measure.

        2. Participants then participate in two sets of non-invasive experiments one after another.
           The BCI system set-up comprising of a laptop connected to a brain signal recorder and a
           headset to record brain signals will be used. Sensors to measure sweat and pulse rate
           will also be used in the experiments. The brain signal recorder together with the
           sensors will be secured in a backpack and worn by participants during the experiments.

      Exp 1-participants watch 15 videos of people doing daily activities. Each video frame is
      approximately 1 min long. EEG signal patterns are recorded for each video frame.

      Exp 2-participants go through a series of 15 physical movements as guided by the
      physiotherapist. Participants are required to complete 15 repetitions each, within 1 min. EEG
      signal patterns are recorded for each movement. Two buzzers (labelled "lesser pain" and "more
      pain") are available for participants to press accordingly should they experience 'lesser' or
      'more' pain at any point during the experiment. If 'more' pain is experienced, the
      physiotherapist will assess the participant's condition and the participant will have a
      choice to either (1) continue the experiment at a lower intensity or (2) stop the experiment.

      Phase 2: Approximately 6 months after participants' participation in Phase 1 and span a
      period of 7 weeks. If selected to complete Phase 2, participants will undergo 18 sessions (3
      sessions/week) of brain training over a period of 6 consecutive weeks. Sessions are conducted
      on alternate days in the week with each session lasting approximately 1 hour. The same system
      set-up used in Phase 1 is used in each training session.

      At the start of the first session in week 1, and immediately after completing the last
      training session in Week 6 participants will also complete the same set of self-report
      questionnaires and the 6-minute walking test (as assessed in Phase 1). At week 7 (1 week post
      training) participants will complete the same full set of measures as set out in the second
      session of Phase 1.

      Phase 3: A total of 2 visits to the study site is required. Each visit will take
      approximately 1 hour 15 minutes. These 2 visits will be scheduled approximately 8.5 mths and
      10.5 mths after completing Phase 1. Both visit sessions involve a repeat of the full set of
      measures that participants completed at the 2nd session in Phase 1.

      Potential Risks

        1. The potential risks to participants are minimal as none of the measures and components
           of the system are invasive. There are currently no known safety issues with the headset
           and sensors. However participants will be kept informed of any new findings.

        2. Participants may experience temporary exertion related discomfort in the main muscle
           groups that are used in the physiotherapy guided movement experiment (Experiment 2)
           although the were designed to fit within participants' abilities. Participants will be
           advised to contact the Principal Investigator (PI) should the muscular discomfort
           persist for more than 24 hours.

        3. If participants are screened positive for depression at any point on the study, the PI
           who is a trained psychologist will screen them for active depression and where
           appropriate refer to the RP for further treatment recommendations. In this case, the
           participant will be excluded or withdrawn from the study.

        4. Due to the potential of the videos and the guided movements to elicit fear of pain,
           participants may experience some increase in anxiety and slight worsening of usual
           pains. Experiment 2 is performed under close supervision of the physiotherapist to
           prevent any possible strain caused by incorrect movements. If participants experience
           'more' pain, the physiotherapist will assess their condition and participants will have
           a choice to either (1) continue the experiment at a lower intensity or (2) stop the
           experiment.

           In the event that participants experience anxiety from participating on any of the
           experiments, the PI will assess their symptoms of anxiety and be able to administer
           appropriate intervention onsite as necessary at no cost. If further treatment is
           required, participants stop the experiment, get re-assessed by the RP and appropriate
           referrals will be made for treatment follow-up.

        5. As no other medication except simple analgesics such as Paracetamol,
           Paracetamol/Orphenadrine, Non-steroidal anti-inflammatory drugs or Tramadol to treat
           pain can be taken while participating on the study, there is a possibility pain may be
           exacerbated and their condition may worsen. If this occurs, the RP will re-assess their
           condition and make appropriate treatment recommendations.

        6. If participants pain condition is exacerbated at any point during the course of the
           study for reasons not indicated in points 1-4 above, they will be referred to the RP on
           the study team for an assessment who will then make appropriate treatment
           recommendations.

        7. if participants develop significant symptoms because of study participation which
           warrants medical intervention, a subsidized medical consult and follow-up treatment will
           be at their own costs. The RP on the study team will facilitate a fast tracked
           appointment at PMC within 2 weeks.

           Study Withdrawal: (a) Participants may withdraw voluntarily from participation in the
           study at any time. Participants may also withdraw voluntarily from receiving the study
           intervention for any reason. If voluntary withdrawal occurs, the participant will not be
           asked to continue scheduled evaluations and their involvement in the study will cease.

           (b) Any participant will be withdrawn from further participation on the study if a
           serious adverse event classified as having a reasonable causal relationship to the study
           occurs. In this case the participant will be given appropriate medical care until the
           symptoms resolve or the condition becomes stable. The participant will not be asked to
           continue scheduled evaluations and their involvement in the study will cease.

           (c) All participants will be withdrawn if there is study closure due to Domain Specific
           Review Board (DSRB) review. Participants who drop out of the study will not be replaced.

           (d) Any participant can be withdrawn from further participation on the study if the
           study team deem it is the best interest of the participant. This can also happen when
           the participant does not follow instructions required to complete the study adequately,
           or develops other medical problems during the study period.

           Specific Restrictions / Requirements:

           (a) Standard over the counter pregnancy testing kits will be used for the purposes of
           determining if a female of childbearing age is pregnant. (b) All forms of contraception
           are allowed during the entire duration of the study (c) Participants are limited to only
           taking simple analgesics such as Paracetamol, Paracetamol/Orphenadrine, Non-steroidal
           anti-inflammatory drugs (NSAIDs) or Tramadol while participating in the study (d) All
           medications (prescription and over the counter), vitamin and mineral supplements, and /
           or herbs taken by the participant will be documented.

           Data analysis: Self-report outcome measures and data from the walking test will be
           analysed via the Statistical Package for the Social Sciences (SPSS) package utilizing
           t-tests to measure group differences and pearson bivariate correlations to measure
           potential relationships between outcome measures and responses made on Exp 1 (video
           condition) and Exp 2 (physiotherapy guided movement condition). EEG patterns will be
           analysed via feature analysis in association with clinical signals and user
           states/condition including physiological measures of skin conductance and pulse rate.

           Data Storage: 1. All hardcopy data, will be stored in designated locked cabinet(s) that
           are accessible to authorized study personnel only. 2. All electronic data, they will be
           stored on in a secured computer that is password-protected. The databases will not
           contain participant identifiers and the data linking participant identifiers and the
           participant identification codes will be stored separately including those using
           portable media (e.g. CD, USB drives etc.).

           Data Access: 1. All study team members will have access to the research data which has
           password protection. 2. Data will not be released and shared with individuals or
           entities outside the institution. 3. Data will be destroyed after it has been stored for
           6 years or minimum duration of retention period as specific by our institutional policy,
           whichever that is longer.

           Data Monitoring: 1. Safety data will be monitored at every visit with participants asked
           to report adverse events since the last visit. 2.There are no anticipated adverse events
           or complications expected. However reported adverse events if any, will be fully
           recorded, graded in terms of severity, and classified as either not related to the
           study, or having a reasonable causal relationship to the study. 3. The PI will be
           responsible for reporting all adverse events to DSRB. If excess risk to the
           participant/s is observed, or a statistically significant benefit is observed, the study
           is stopped early and the patient informed of the results. Futility is not used as a
           stopping criteria as this is a feasibility trial design of which there is limited data,
           and of a small sample size. The final study results are needed to proof the study
           concept here. 4. The PI will be responsible for the dissemination of any data and safety
           information to the study site. Communication will be conducted weekly via secure e-mail
           to the study team during active phase of the study in Phase 1, 2 and 3. A monthly
           face-to-face meetings and where necessary ad hoc meetings during the period of the
           study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Assessing change in Numerical pain rating scale
time frame: Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9
description: Measure of pain intensity
measure: Assessing change in Tampa Kinesiophobia Scale (Miller et al., 1991)
time frame: Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9
description: Measure of fear-avoidance
measure: Assessing change in Photograph series of daily activities (PHODA-SeV) scale (Leeuw et al., 2007)
time frame: Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9
description: Measure of patients' perceptions about the consequences of harmful situations based on a series of photographs
measure: Assessing change in Pain Interference Scale on the Brief Pain Inventory (BPI) (Cleeland & Ryan, 1994)
time frame: Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9
description: Measure of pain interference on daily activities
measure: Assessing change in Short-form 36 questionnaire (SF-36) (Ware & Sherbourne, 1992)
time frame: Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9
description: Measure of quality of life
measure: Assessing change in Patient Health Questionnaire-9 (PHQ-9) (Spitzer et al., 1999)
time frame: Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9
description: Measure of Depressive Symptoms
measure: Assessing change in Pain Catastrophizing Scale (PCS) (Sullivan et al., 1995)
time frame: Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9
description: Measure of pain related catastrophizing
measure: Assessing change in 6 minute Shuttle Walk Test
time frame: Phase 1: week 1; Phase 2: Week 1, Week 6 and Week 7; Phase 3: Week 1 and week 9
description: Objective measure of disability
arm group label: EEG-based BCI analysis of fear avoidance
arm group type: Experimental
description: All participants complete two experiments one after another-EEG patterns, skin conductance and pulse rate are recorded. The EEG cap is mounted on the participant's head, the GSR sensor secured on the fingers and the PPG sensor secured on the wrist using a Velcro strap. Exp 1-participants watch a series of 15, 1 min videos of people doing daily activities. Exp 2-participants do 15 movements (15 reps each in 1 min) as guided by a physiotherapist. 2 identical buzzers (labelled "lesser pain" and "more pain") are available to press accordingly should participants experience 'lesser' or 'more' pain any time during the experiment. If 'more' pain experienced, participants' condition will be assessed and they can choose to continue the experiment at a lower intensity or stop.
intervention type: Device
intervention name: EEG-based BCI analysis of fear avoidance
description: Scalp EEG signals that are acquired and recorded from experiment 1 and 2 are analysed for healthy controls, participants with low back pain and participants with lower limb pain. Comparisons of signal patterns are made between groups. Assuming unique signal patterns are obtained for each groups, these signals are further analysed and used to develop a feedback brain training system to better manage pain and ideally reduce fear-avoidant behaviors towards pain.
arm group label: EEG-based BCI analysis of fear avoidance
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Su-Yin Yang, PhD
role: Principal Investigator
affiliation: Tan Tock Seng Hospital
facility: 
country: Singapore
citation: Jensen MP, Sherlin LH, Fregni F, Gianas A, Howe JD, Hakimian S. Baseline brain activity predicts response to neuromodulatory pain treatment. Pain Med. 2014 Dec;15(12):2055-63. doi: 10.1111/pme.12546. Epub 2014 Oct 7.
PMID: 25287554
citation: Jensen MP, Hakimian S, Sherlin LH, Fregni F. New insights into neuromodulatory approaches for the treatment of pain. J Pain. 2008 Mar;9(3):193-9. doi: 10.1016/j.jpain.2007.11.003. Epub 2007 Dec 21.
PMID: 18096437
citation: Pinheiro ES, de Queiros FC, Montoya P, Santos CL, do Nascimento MA, Ito CH, Silva M, Nunes Santos DB, Benevides S, Miranda JG, Sa KN, Baptista AF. Electroencephalographic Patterns in Chronic Pain: A Systematic Review of the Literature. PLoS One. 2016 Feb 25;11(2):e0149085. doi: 10.1371/journal.pone.0149085. eCollection 2016.
PMID: 26914356
responsible party type: Sponsor
mesh term: Chronic Pain
sharing ipd: No
ipd description: There is no plan to make IPD available to other researchers.