<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/NCT04468074</url>
  </required_header>
  <id_info>
    <org_study_id>19-0526</org_study_id>
    <secondary_id>1R43NR017575-01A1</secondary_id>
    <nct_id>NCT04468074</nct_id>
  </id_info>
  <brief_title>Virtual Reality Treatment for Adults With Chronic Back Pain</brief_title>
  <official_title>Study on the Use of Virtual Reality Neuropsychological Therapy Technology (VRNT) for Chronic Back Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CognifiSense Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Colorado, Boulder</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Nursing Research (NINR)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>CognifiSense Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Participants with chronic back pain will complete an online eligibility questionnaire. After&#xD;
      signing a consent form, eligible participants enter a two-week baseline period (&quot;Baseline&#xD;
      Period&quot;) during which they complete a daily pain survey. Following the Baseline Period all&#xD;
      participants complete an MRI scan. After the MRI, scan participants are randomized into a&#xD;
      treatment group (&quot;Therapy Group&quot;) or a no-intervention group (&quot;Standard of Care Group&quot; or&#xD;
      &quot;SOC Group&quot;) with a ratio of 1:1 (treatment:SOC). Therapy Group participants receive&#xD;
      education about chronic pain. They also participate in sessions to personalize their Virtual&#xD;
      Reality (VR) experience, and to complete training on the use of the VR hardware and software.&#xD;
      Therapy Group participants complete the treatment for 8 weeks (&quot;Therapy Period&quot;), after which&#xD;
      they return the VR equipment. All participants take a second MRI scan approximately 8-weeks&#xD;
      after the first MRI; for the Therapy Group this is at the end of the Therapy Period. After&#xD;
      the Therapy Period, Therapy Group participants continue to complete daily pain surveys during&#xD;
      a two-week follow-up period (&quot;Follow-Up Period&quot;). All participants complete self-reported&#xD;
      clinical outcomes and behavioral measures surveys before and after the Baseline Period, 4&#xD;
      weeks after the first MRI (for Therapy Group this is mid-way through the Therapy Period), and&#xD;
      before and after the Follow-Up Period. For Therapy Group participants the study ends with the&#xD;
      final surveys and an exit interview at the end of the Follow-up Period. Study Extension&#xD;
      (Add-on): SOC Group participants may receive the treatment after the Follow-Up period. Those&#xD;
      who elect to do so will complete the same set of surveys as the Therapy Group did during the&#xD;
      treatment phase; however, since there is no comparison group, data from this study extension&#xD;
      is not used in the main outcomes analyses.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 9, 2020</start_date>
  <completion_date type="Actual">June 14, 2021</completion_date>
  <primary_completion_date type="Actual">April 13, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Pain Intensity and Interference.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Brief Pain Inventory-short form (BPI-SF). Measured on Scale of 0 to 10, 0 = no pain, 10 = worst pain imaginable.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of Life.</measure>
    <time_frame>Baseline (average of survey data at beginning and end of a 2-week baseline period) and at the end of the 8 week therapy / control period.</time_frame>
    <description>Quality of Life (HRQoL SF-12) Questionnaire: yes / no questions and 3-point / 6-point Likert Scale questions; e.g., 1 = [negative impact] all of the time (worse outcome), 6 = [negative impact] none of the time. HRQoL results in two sub-scales / components (Physical and Mental). The mean of these was taken to result in a single value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Back Pain Disability.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Oswestry Low Back Pain Disability Questionnaire (OLBPD). 6-point Likert Scale questions on impact of pain on various life aspects; e.g., 1 = no negative impact, 6 = prevents normal activity (worse outcome). Participants completed questionnaire at the beginning and end of a 2-week baseline period and at the end of the 8 week therapy / control period. The starting values were the average of the two reported pain measures at the beginning and end of the baseline period</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in Pain Bothersomeness.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Pain Bothersomeness Scale. 0-10 scale: 0 = not at all bothersome; 10 = extremely bothersome) (Source: Cherkin et al. 2016).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Medications and Therapies.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>A questionnaire asking participants to list the type and dosage / frequency of medication and therapies the participant is using for their back pain and for any other medical conditions. The list and dosage of medications and the type and frequencies of therapies will be compared pre- and post-treatment (8-week interval) to assess change in other pain therapies.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Pain Catastrophizing.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Pain Catastrophizing Questionnaire (PCS). 4-point Likert scale: = not at all, 4 = all the time (worse outcome).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Fear of Pain.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Fear of Pain Questionnaire. 5-point Likert scale: = not at all, 5 = extreme (worse outcome).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Fear of Movement.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Tampa Scale of Kinesiophobia (TSK). 4-point Likert scale: = strongly disagree, 4 = strongly agree (worse outcome).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Sleep Quality.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Patient Reported Outcomes Measurement Information System (PROMIS) short form for Sleep Disturbance: 8 items. 5-point Likert scales: 5 = not at all, 1 = very much (worse outcome).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Fatigue Symptoms.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Patient Reported Outcomes Measurement Information System (PROMIS) short form for Fatigue: 8 items. 5-point Likert scales: 1 = not at all, 5 = very much (worse outcome).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Depression.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Patient Reported Outcomes Measurement Information System (PROMIS) short form for Depression: 8 items. 5-point Likert scales: 5 = never, 1 = always (worse outcome).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Pain Attitudes.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Survey of Pain Attitudes (SOPA) Short Form. 6-point Likert scale: 5 = This is very untrue for me, 1 = This is very true for me [worse outcome].</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Self-efficacy.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>General Self-Efficacy Scale. 4-point Likert scale: 1 = not at all true [worse outcome], 4 = exactly true.</description>
  </other_outcome>
  <other_outcome>
    <measure>Expectations of Treatment Success.</measure>
    <time_frame>Before Therapy Period begins (pre-treatment; after 2-week baseline).</time_frame>
    <description>Expectations of Treatment Success Survey. 0 to 10 scale: 0 = none, 10 = most (best outcome).</description>
  </other_outcome>
  <other_outcome>
    <measure>Impression of Treatment Success.</measure>
    <time_frame>At the end of the Therapy Period (post-treatment; approx. 10 weeks into study).</time_frame>
    <description>Patient Global Impression of Change (PGIC). 7-point scale: 0 = no change (condition has got worse [worst outcome]), 10 = a great deal better, and a considerable improvement that has made all the difference.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Optimism</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Life Orientation Test (LOT-R). 5-point Likert scale: 0 = strongly disagree, 4 = strongly agree (worse outcome is a function of the question).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Emotion Regulation.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Emotion Regulation Questionnaire (ERQ). 7-point Likert scale: 1 = strongly disagree, 7 = strongly agree (worse outcome is a function of the question).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Mindfulness.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Mindful Attention Awareness Scale (MAAS). 7-point Likert scale: 0 = almost always (worse outcome), 7 = almost never.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Pain Coping Strategies.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Coping Strategies Questionnaire (CSQ). 7-point Likert scale: 0 = never do, 7 = always do that (worse outcome is a function of the question).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Structural (Brain) MRI.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Acquire 2 structural MRI brain scans (before and after treatment) to measure brain gray matter changes due to treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Resting-State Functional MRI.</measure>
    <time_frame>from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Acquire 2 functional MRI brain scans (before and after treatment), during which the participants will rest, to measure functional brain changes due to treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Diffusion Tensor Imaging (DTI) MRI.</measure>
    <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
    <description>Acquire 2 DTI MRI scans (before and after treatment) to measure brain white matter changes due to treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Assessment of Usability of VR Device.</measure>
    <time_frame>At the end of the Therapy Period (post-treatment; approx. 10 weeks into study).</time_frame>
    <description>Questionnaire with 10 questions on usability of the VR device; 5-point Likert scale: 1 = strongly disagree, 5 = strongly agree (worse outcome is a function of the question).</description>
  </other_outcome>
  <other_outcome>
    <measure>Assessment of Sense of Presence in the VR Environment.</measure>
    <time_frame>At the end of the Therapy Period (post-treatment; approx. 10 weeks into study).</time_frame>
    <description>Questionnaire with 14 questions about the participant's sense of presence in the virtual environment - based on IGP Presence Questionnaire; 5-point Likert scale: 1 = fully disagree, 5 = fully agree (worse outcome is a function of the question).</description>
  </other_outcome>
  <other_outcome>
    <measure>Assessment of Sense of Embodiment in the VR Environment.</measure>
    <time_frame>At the end of the Therapy Period (post-treatment; approx. 10 weeks into study)</time_frame>
    <description>Questionnaire with 10 questions about the participant's sense of embodiment in the virtual reality environment - based on the Gonzalez-Franko Embodiment Questionnaire; 7-point Likert scale from -3 = strongly disagree to +3 = strongly agree (worse outcome is a function of the question).</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Chronic Pain</condition>
  <condition>Back Pain Lower Back Chronic</condition>
  <condition>Back Pain</condition>
  <arm_group>
    <arm_group_label>Therapy Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Therapy Group participants start the treatment period with three 1 ½ hour introductory sessions:&#xD;
An education session on the science behind chronic pain and a basic overview of the VR therapy.&#xD;
A session to customize the VR experience to match the participant's own pain experience.&#xD;
A training session on the use of the VR hardware and software.&#xD;
Upon completion, participants begin using the VR therapy app at home once a day, 5 times a week (minimum), for a total of 8 weeks. The VR app contains different training exercises. A workbook provides a schedule and background on each of the training sessions.&#xD;
Therapy Group participants may continue their other pain treatment regimes, and are asked to notify the research team of any changes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care (SOC) Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The SOC Group (no-intervention) completes a daily pain survey. SOC Group participants are asked to maintain their pain treatment regimes, and are asked to notify the research team of any changes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Virtual Reality Therapy for Chronic Pain</intervention_name>
    <description>A 1 1/2 PowerPoint-based education session on the science behind chronic pain and a basic overview of the VR therapy&#xD;
Virtual Reality Therapy: a virtual reality therapy consisting of different psychological training exercises</description>
    <arm_group_label>Therapy Group</arm_group_label>
    <other_name>Virtual Reality Neuropsychological Therapy (VRNT)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants aged 21 to 70 with Chronic Back Pain.&#xD;
&#xD;
          -  Chronic Back Pain will be defined according to criteria established by recent NIH task&#xD;
             force. Pain duration must be ≥ 3 months, with back pain being an ongoing problem for&#xD;
             at least half the days of last 6 months; i.e., either pain every day for past 3&#xD;
             months, or half or more of the days for past 6+ months.&#xD;
&#xD;
          -  Subjects must rate pain intensity at ≥ 4/10 on Brief Pain Inventory (average pain over&#xD;
             the last week).&#xD;
&#xD;
          -  Participants must also be comfortable and able to communicate via email, text message,&#xD;
             or phone in English. Participants must also be comfortable using a video-conferencing&#xD;
             service such as Zoom to complete the on-line sessions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Applicants, who are pregnant, planning pregnancy, or breastfeeding&#xD;
&#xD;
          -  Back pain associated with compensation / litigation within 1 year.&#xD;
&#xD;
          -  Leg pain greater than back pain (suggests neuropathic pain; may be less responsive to&#xD;
             psychological therapy).&#xD;
&#xD;
          -  Chronic pain other than chronic back pain.&#xD;
&#xD;
          -  Diagnoses of schizophrenia, multiple personality dissociative identity disorder.&#xD;
&#xD;
          -  History of major depressive disorder not controlled with medication or other&#xD;
             conditions that produce significant cognitive or emotional disability.&#xD;
&#xD;
          -  History of substance abuse.&#xD;
&#xD;
          -  Inability to undergo MRI (determined at screening; see XVI: Risks to Participants).&#xD;
&#xD;
          -  Any clinically significant unstable medical abnormality or acute or chronic disease of&#xD;
             cardiovascular, gastrointestinal, respiratory (e.g., chronic obstructive pulmonary&#xD;
             disease), hepatic, or renal systems; including: history of cardiovascular disease or&#xD;
             issues (e.g., recent heart attack), stroke; brain surgery, or brain tumor; Diabetes;&#xD;
             cancer (last 12 months); diagnosis of a specific inflammatory disorder: rheumatoid&#xD;
             arthritis, polymyalgia rheumatica, scleroderma, Lupus; polymyositis; or Cauda Equina&#xD;
             syndrome.&#xD;
&#xD;
          -  History of seizure disorder, epilepsy, convulsions, or increased intracranial pressure&#xD;
             anytime except pediatric febrile seizures.&#xD;
&#xD;
          -  History of vertigo, dizziness, susceptibility to motion sickness&#xD;
&#xD;
          -  History of head injury within 6 months,&#xD;
&#xD;
          -  Unexplained, unintended weight loss of 'â• 20 lbs in past year.&#xD;
&#xD;
          -  Self-reported history of (digital) eye strain or computer vision syndrome.&#xD;
&#xD;
          -  Unable or unwilling to meet study attendance requirements.&#xD;
&#xD;
          -  MRI contraindications as determined by MRI safety screen (e.g., pregnancy, metal in&#xD;
             body, claustrophobia, using the standard screen conducted by the MRI imaging&#xD;
             facility).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marta Ceko, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Boulder</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lynn Webster, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CognifiSense Inc.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Tassilo Baeuerle</last_name>
    <role>Principal Investigator</role>
    <affiliation>CognifiSense Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado, Boulder</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Cherkin DC, Sherman KJ, Balderson BH, Cook AJ, Anderson ML, Hawkes RJ, Hansen KE, Turner JA. Effect of Mindfulness-Based Stress Reduction vs Cognitive Behavioral Therapy or Usual Care on Back Pain and Functional Limitations in Adults With Chronic Low Back Pain: A Randomized Clinical Trial. JAMA. 2016 Mar 22-29;315(12):1240-9. doi: 10.1001/jama.2016.2323.</citation>
    <PMID>27002445</PMID>
  </reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <results_first_submitted>April 13, 2022</results_first_submitted>
  <results_first_submitted_qc>May 27, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 23, 2022</results_first_posted>
  <last_update_submitted>May 27, 2022</last_update_submitted>
  <last_update_submitted_qc>May 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2022</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>Back Pain</mesh_term>
    <mesh_term>Chronic Pain</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 29, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT04468074/Prot_003.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 12, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT04468074/SAP_004.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 19, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT04468074/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited via online (e.g., social media) advertising between December 2019 and September 2020. The first participant was enrolled on June 9, 2020, and the last participant was enrolled in October 2020.</recruitment_details>
      <pre_assignment_details>Of 1,346 applicants, 270 met inclusion criteria. Of these, 72 were enrolled in the study; however, 11 withdrew before start / randomization. 61 participants started the study (completed randomization). After a 2-week baseline period, participants were randomized into the Experimental and No Intervention Groups.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Therapy Group</title>
          <description>Therapy Group participants start the treatment period with three 1 ½ hour introductory sessions:&#xD;
An education session on the science behind chronic pain and a basic overview of the VR therapy.&#xD;
A session to customize the VR experience to match the participant's own pain experience.&#xD;
A training session on the use of the VR hardware and software.&#xD;
Upon completion, participants begin using the VR therapy app at home once a day, 5 times a week (minimum), for a total of 8 weeks. The VR app contains different training exercises. A workbook provides a schedule and background on each of the training sessions.&#xD;
Therapy Group participants may continue their other pain treatment regimes, and are asked to notify the research team of any changes.&#xD;
Virtual Reality Therapy for Chronic Pain: 1) A 1 1/2 PowerPoint-based education session on the science behind chronic pain and a basic overview of the VR therapy 2) Virtual Reality Therapy: a virtual reality therapy consisting of different psychological training exercises</description>
        </group>
        <group group_id="P2">
          <title>Standard of Care (SOC) Group</title>
          <description>The SOC Group (no-intervention) completes a daily pain survey. SOC Group participants are asked to maintain their pain treatment regimes, and are asked to notify the research team of any changes.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Therapy Group</title>
          <description>Therapy Group participants start the treatment period with three 1 ½ hour introductory sessions:&#xD;
An education session on the science behind chronic pain and a basic overview of the VR therapy.&#xD;
A session to customize the VR experience to match the participant's own pain experience.&#xD;
A training session on the use of the VR hardware and software.&#xD;
Upon completion, participants begin using the VR therapy app at home once a day, 5 times a week (minimum), for a total of 8 weeks. The VR app contains different training exercises. A workbook provides a schedule and background on each of the training sessions.&#xD;
Therapy Group participants may continue their other pain treatment regimes, and are asked to notify the research team of any changes.&#xD;
Virtual Reality Therapy for Chronic Pain: 1) A 1 1/2 PowerPoint-based education session on the science behind chronic pain and a basic overview of the VR therapy 2) Virtual Reality Therapy: a virtual reality therapy consisting of different psychological training exercises</description>
        </group>
        <group group_id="B2">
          <title>Standard of Care (SOC) Group</title>
          <description>The SOC Group (no-intervention) completes a daily pain survey. SOC Group participants are asked to maintain their pain treatment regimes, and are asked to notify the research team of any changes.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="31"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="61"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35.1" spread="10"/>
                    <measurement group_id="B2" value="33.5" spread="9.2"/>
                    <measurement group_id="B3" value="34.2" spread="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Pain Intensity and Interference.</title>
        <description>Brief Pain Inventory-short form (BPI-SF). Measured on Scale of 0 to 10, 0 = no pain, 10 = worst pain imaginable.</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Therapy Group</title>
            <description>Therapy Group participants start the treatment period with three 1 ½ hour introductory sessions:&#xD;
An education session on the science behind chronic pain and a basic overview of the VR therapy.&#xD;
A session to customize the VR experience to match the participant's own pain experience.&#xD;
A training session on the use of the VR hardware and software.&#xD;
Upon completion, participants begin using the VR therapy app at home once a day, 5 times a week (minimum), for a total of 8 weeks. The VR app contains different training exercises. A workbook provides a schedule and background on each of the training sessions.&#xD;
Therapy Group participants may continue their other pain treatment regimes, and are asked to notify the research team of any changes.&#xD;
Virtual Reality Therapy for Chronic Pain: 1) A 1 1/2 PowerPoint-based education session on the science behind chronic pain and a basic overview of the VR therapy 2) Virtual Reality Therapy: a virtual reality therapy consisting of different psychological training exercises</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care (SOC) Group</title>
            <description>The SOC Group (no-intervention) completes a daily pain survey. SOC Group participants are asked to maintain their pain treatment regimes, and are asked to notify the research team of any changes.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Pain Intensity and Interference.</title>
          <description>Brief Pain Inventory-short form (BPI-SF). Measured on Scale of 0 to 10, 0 = no pain, 10 = worst pain imaginable.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" spread="1.7"/>
                    <measurement group_id="O2" value="-0.5" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.014</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>1</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Quality of Life.</title>
        <description>Quality of Life (HRQoL SF-12) Questionnaire: yes / no questions and 3-point / 6-point Likert Scale questions; e.g., 1 = [negative impact] all of the time (worse outcome), 6 = [negative impact] none of the time. HRQoL results in two sub-scales / components (Physical and Mental). The mean of these was taken to result in a single value.</description>
        <time_frame>Baseline (average of survey data at beginning and end of a 2-week baseline period) and at the end of the 8 week therapy / control period.</time_frame>
        <population>Intent to Treat</population>
        <group_list>
          <group group_id="O1">
            <title>Therapy Group</title>
            <description>Therapy Group participants start the treatment period with three 1 ½ hour introductory sessions:&#xD;
An education session on the science behind chronic pain and a basic overview of the VR therapy.&#xD;
A session to customize the VR experience to match the participant's own pain experience.&#xD;
A training session on the use of the VR hardware and software.&#xD;
Upon completion, participants begin using the VR therapy app at home once a day, 5 times a week (minimum), for a total of 8 weeks. The VR app contains different training exercises. A workbook provides a schedule and background on each of the training sessions.&#xD;
Therapy Group participants may continue their other pain treatment regimes, and are asked to notify the research team of any changes.&#xD;
Virtual Reality Therapy for Chronic Pain: 1) A 1 1/2 PowerPoint-based education session on the science behind chronic pain and a basic overview of the VR therapy 2) Virtual Reality Therapy: a virtual reality therapy consisting of different psychological training exercises</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care (SOC) Group</title>
            <description>The SOC Group (no-intervention) completes a daily pain survey. SOC Group participants are asked to maintain their pain treatment regimes, and are asked to notify the research team of any changes.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Quality of Life.</title>
          <description>Quality of Life (HRQoL SF-12) Questionnaire: yes / no questions and 3-point / 6-point Likert Scale questions; e.g., 1 = [negative impact] all of the time (worse outcome), 6 = [negative impact] none of the time. HRQoL results in two sub-scales / components (Physical and Mental). The mean of these was taken to result in a single value.</description>
          <population>Intent to Treat</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.68" spread="4.7"/>
                    <measurement group_id="O2" value=".89" spread="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0159</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>2.79</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Back Pain Disability.</title>
        <description>Oswestry Low Back Pain Disability Questionnaire (OLBPD). 6-point Likert Scale questions on impact of pain on various life aspects; e.g., 1 = no negative impact, 6 = prevents normal activity (worse outcome). Participants completed questionnaire at the beginning and end of a 2-week baseline period and at the end of the 8 week therapy / control period. The starting values were the average of the two reported pain measures at the beginning and end of the baseline period</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Therapy Group</title>
            <description>Therapy Group participants start the treatment period with three 1 ½ hour introductory sessions:&#xD;
An education session on the science behind chronic pain and a basic overview of the VR therapy.&#xD;
A session to customize the VR experience to match the participant's own pain experience.&#xD;
A training session on the use of the VR hardware and software.&#xD;
Upon completion, participants begin using the VR therapy app at home once a day, 5 times a week (minimum), for a total of 8 weeks. The VR app contains different training exercises. A workbook provides a schedule and background on each of the training sessions.&#xD;
Therapy Group participants may continue their other pain treatment regimes, and are asked to notify the research team of any changes.&#xD;
Virtual Reality Therapy for Chronic Pain: 1) A 1 1/2 PowerPoint-based education session on the science behind chronic pain and a basic overview of the VR therapy 2) Virtual Reality Therapy: a virtual reality therapy consisting of different psychological training exercises</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care (SOC) Group</title>
            <description>The SOC Group (no-intervention) completes a daily pain survey. SOC Group participants are asked to maintain their pain treatment regimes, and are asked to notify the research team of any changes.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Back Pain Disability.</title>
          <description>Oswestry Low Back Pain Disability Questionnaire (OLBPD). 6-point Likert Scale questions on impact of pain on various life aspects; e.g., 1 = no negative impact, 6 = prevents normal activity (worse outcome). Participants completed questionnaire at the beginning and end of a 2-week baseline period and at the end of the 8 week therapy / control period. The starting values were the average of the two reported pain measures at the beginning and end of the baseline period</description>
          <population>Intent to treat</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.22" spread="6.2"/>
                    <measurement group_id="O2" value="-.37" spread="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0066</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Median Difference (Net)</param_type>
            <param_value>-3.85</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Pain Bothersomeness.</title>
        <description>Pain Bothersomeness Scale. 0-10 scale: 0 = not at all bothersome; 10 = extremely bothersome) (Source: Cherkin et al. 2016).</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Medications and Therapies.</title>
        <description>A questionnaire asking participants to list the type and dosage / frequency of medication and therapies the participant is using for their back pain and for any other medical conditions. The list and dosage of medications and the type and frequencies of therapies will be compared pre- and post-treatment (8-week interval) to assess change in other pain therapies.</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Pain Catastrophizing.</title>
        <description>Pain Catastrophizing Questionnaire (PCS). 4-point Likert scale: = not at all, 4 = all the time (worse outcome).</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Fear of Pain.</title>
        <description>Fear of Pain Questionnaire. 5-point Likert scale: = not at all, 5 = extreme (worse outcome).</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Fear of Movement.</title>
        <description>Tampa Scale of Kinesiophobia (TSK). 4-point Likert scale: = strongly disagree, 4 = strongly agree (worse outcome).</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Sleep Quality.</title>
        <description>Patient Reported Outcomes Measurement Information System (PROMIS) short form for Sleep Disturbance: 8 items. 5-point Likert scales: 5 = not at all, 1 = very much (worse outcome).</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Fatigue Symptoms.</title>
        <description>Patient Reported Outcomes Measurement Information System (PROMIS) short form for Fatigue: 8 items. 5-point Likert scales: 1 = not at all, 5 = very much (worse outcome).</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Depression.</title>
        <description>Patient Reported Outcomes Measurement Information System (PROMIS) short form for Depression: 8 items. 5-point Likert scales: 5 = never, 1 = always (worse outcome).</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Pain Attitudes.</title>
        <description>Survey of Pain Attitudes (SOPA) Short Form. 6-point Likert scale: 5 = This is very untrue for me, 1 = This is very true for me [worse outcome].</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Self-efficacy.</title>
        <description>General Self-Efficacy Scale. 4-point Likert scale: 1 = not at all true [worse outcome], 4 = exactly true.</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Expectations of Treatment Success.</title>
        <description>Expectations of Treatment Success Survey. 0 to 10 scale: 0 = none, 10 = most (best outcome).</description>
        <time_frame>Before Therapy Period begins (pre-treatment; after 2-week baseline).</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Impression of Treatment Success.</title>
        <description>Patient Global Impression of Change (PGIC). 7-point scale: 0 = no change (condition has got worse [worst outcome]), 10 = a great deal better, and a considerable improvement that has made all the difference.</description>
        <time_frame>At the end of the Therapy Period (post-treatment; approx. 10 weeks into study).</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Optimism</title>
        <description>Life Orientation Test (LOT-R). 5-point Likert scale: 0 = strongly disagree, 4 = strongly agree (worse outcome is a function of the question).</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Emotion Regulation.</title>
        <description>Emotion Regulation Questionnaire (ERQ). 7-point Likert scale: 1 = strongly disagree, 7 = strongly agree (worse outcome is a function of the question).</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Mindfulness.</title>
        <description>Mindful Attention Awareness Scale (MAAS). 7-point Likert scale: 0 = almost always (worse outcome), 7 = almost never.</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Pain Coping Strategies.</title>
        <description>Coping Strategies Questionnaire (CSQ). 7-point Likert scale: 0 = never do, 7 = always do that (worse outcome is a function of the question).</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Structural (Brain) MRI.</title>
        <description>Acquire 2 structural MRI brain scans (before and after treatment) to measure brain gray matter changes due to treatment.</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Resting-State Functional MRI.</title>
        <description>Acquire 2 functional MRI brain scans (before and after treatment), during which the participants will rest, to measure functional brain changes due to treatment.</description>
        <time_frame>from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Diffusion Tensor Imaging (DTI) MRI.</title>
        <description>Acquire 2 DTI MRI scans (before and after treatment) to measure brain white matter changes due to treatment.</description>
        <time_frame>Change from pre-treatment to post-treatment = 8 weeks.</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Assessment of Usability of VR Device.</title>
        <description>Questionnaire with 10 questions on usability of the VR device; 5-point Likert scale: 1 = strongly disagree, 5 = strongly agree (worse outcome is a function of the question).</description>
        <time_frame>At the end of the Therapy Period (post-treatment; approx. 10 weeks into study).</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Assessment of Sense of Presence in the VR Environment.</title>
        <description>Questionnaire with 14 questions about the participant's sense of presence in the virtual environment - based on IGP Presence Questionnaire; 5-point Likert scale: 1 = fully disagree, 5 = fully agree (worse outcome is a function of the question).</description>
        <time_frame>At the end of the Therapy Period (post-treatment; approx. 10 weeks into study).</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Assessment of Sense of Embodiment in the VR Environment.</title>
        <description>Questionnaire with 10 questions about the participant's sense of embodiment in the virtual reality environment - based on the Gonzalez-Franko Embodiment Questionnaire; 7-point Likert scale from -3 = strongly disagree to +3 = strongly agree (worse outcome is a function of the question).</description>
        <time_frame>At the end of the Therapy Period (post-treatment; approx. 10 weeks into study)</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Therapy Group</title>
          <description>Therapy Group participants start the treatment period with three 1 ½ hour introductory sessions:&#xD;
An education session on the science behind chronic pain and a basic overview of the VR therapy.&#xD;
A session to customize the VR experience to match the participant's own pain experience.&#xD;
A training session on the use of the VR hardware and software.&#xD;
Upon completion, participants begin using the VR therapy app at home once a day, 5 times a week (minimum), for a total of 8 weeks. The VR app contains different training exercises. A workbook provides a schedule and background on each of the training sessions.&#xD;
Therapy Group participants may continue their other pain treatment regimes, and are asked to notify the research team of any changes.&#xD;
Virtual Reality Therapy for Chronic Pain: 1) A 1 1/2 PowerPoint-based education session on the science behind chronic pain and a basic overview of the VR therapy 2) Virtual Reality Therapy: a virtual reality therapy consisting of different psychological training exercises</description>
        </group>
        <group group_id="E2">
          <title>Standard of Care (SOC) Group</title>
          <description>The SOC Group (no-intervention) completes a daily pain survey. SOC Group participants are asked to maintain their pain treatment regimes, and are asked to notify the research team of any changes.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Marta Ceko</name_or_title>
      <organization>University of Colorado, Boulder</organization>
      <phone>443-835-6587</phone>
      <email>Marta.Ceko@colorado.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04468074
org study id: 19-0526
secondary id: 1R43NR017575-01A1
nct id: NCT04468074
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
is us export: No
Participants with chronic back pain will complete an online eligibility questionnaire. After
      signing a consent form, eligible participants enter a two-week baseline period ("Baseline
      Period") during which they complete a daily pain survey. Following the Baseline Period all
      participants complete an MRI scan. After the MRI, scan participants are randomized into a
      treatment group ("Therapy Group") or a no-intervention group ("Standard of Care Group" or
      "SOC Group") with a ratio of 1:1 (treatment:SOC). Therapy Group participants receive
      education about chronic pain. They also participate in sessions to personalize their Virtual
      Reality (VR) experience, and to complete training on the use of the VR hardware and software.
      Therapy Group participants complete the treatment for 8 weeks ("Therapy Period"), after which
      they return the VR equipment. All participants take a second MRI scan approximately 8-weeks
      after the first MRI; for the Therapy Group this is at the end of the Therapy Period. After
      the Therapy Period, Therapy Group participants continue to complete daily pain surveys during
      a two-week follow-up period ("Follow-Up Period"). All participants complete self-reported
      clinical outcomes and behavioral measures surveys before and after the Baseline Period, 4
      weeks after the first MRI (for Therapy Group this is mid-way through the Therapy Period), and
      before and after the Follow-Up Period. For Therapy Group participants the study ends with the
      final surveys and an exit interview at the end of the Follow-up Period. Study Extension
      (Add-on): SOC Group participants may receive the treatment after the Follow-Up period. Those
      who elect to do so will complete the same set of surveys as the Therapy Group did during the
      treatment phase; however, since there is no comparison group, data from this study extension
      is not used in the main outcomes analyses.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Change in Pain Intensity and Interference.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Brief Pain Inventory-short form (BPI-SF). Measured on Scale of 0 to 10, 0 = no pain, 10 = worst pain imaginable.
measure: Change in Quality of Life.
time frame: Baseline (average of survey data at beginning and end of a 2-week baseline period) and at the end of the 8 week therapy / control period.
description: Quality of Life (HRQoL SF-12) Questionnaire: yes / no questions and 3-point / 6-point Likert Scale questions; e.g., 1 = [negative impact] all of the time (worse outcome), 6 = [negative impact] none of the time. HRQoL results in two sub-scales / components (Physical and Mental). The mean of these was taken to result in a single value.
measure: Change in Back Pain Disability.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Oswestry Low Back Pain Disability Questionnaire (OLBPD). 6-point Likert Scale questions on impact of pain on various life aspects; e.g., 1 = no negative impact, 6 = prevents normal activity (worse outcome). Participants completed questionnaire at the beginning and end of a 2-week baseline period and at the end of the 8 week therapy / control period. The starting values were the average of the two reported pain measures at the beginning and end of the baseline period
measure: Change in Pain Bothersomeness.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Pain Bothersomeness Scale. 0-10 scale: 0 = not at all bothersome; 10 = extremely bothersome) (Source: Cherkin et al. 2016).
measure: Change in Medications and Therapies.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: A questionnaire asking participants to list the type and dosage / frequency of medication and therapies the participant is using for their back pain and for any other medical conditions. The list and dosage of medications and the type and frequencies of therapies will be compared pre- and post-treatment (8-week interval) to assess change in other pain therapies.
measure: Change in Pain Catastrophizing.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Pain Catastrophizing Questionnaire (PCS). 4-point Likert scale: = not at all, 4 = all the time (worse outcome).
measure: Change in Fear of Pain.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Fear of Pain Questionnaire. 5-point Likert scale: = not at all, 5 = extreme (worse outcome).
measure: Change in Fear of Movement.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Tampa Scale of Kinesiophobia (TSK). 4-point Likert scale: = strongly disagree, 4 = strongly agree (worse outcome).
measure: Change in Sleep Quality.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Patient Reported Outcomes Measurement Information System (PROMIS) short form for Sleep Disturbance: 8 items. 5-point Likert scales: 5 = not at all, 1 = very much (worse outcome).
measure: Change in Fatigue Symptoms.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Patient Reported Outcomes Measurement Information System (PROMIS) short form for Fatigue: 8 items. 5-point Likert scales: 1 = not at all, 5 = very much (worse outcome).
measure: Change in Depression.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Patient Reported Outcomes Measurement Information System (PROMIS) short form for Depression: 8 items. 5-point Likert scales: 5 = never, 1 = always (worse outcome).
measure: Change in Pain Attitudes.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Survey of Pain Attitudes (SOPA) Short Form. 6-point Likert scale: 5 = This is very untrue for me, 1 = This is very true for me [worse outcome].
measure: Change in Self-efficacy.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: General Self-Efficacy Scale. 4-point Likert scale: 1 = not at all true [worse outcome], 4 = exactly true.
measure: Expectations of Treatment Success.
time frame: Before Therapy Period begins (pre-treatment; after 2-week baseline).
description: Expectations of Treatment Success Survey. 0 to 10 scale: 0 = none, 10 = most (best outcome).
measure: Impression of Treatment Success.
time frame: At the end of the Therapy Period (post-treatment; approx. 10 weeks into study).
description: Patient Global Impression of Change (PGIC). 7-point scale: 0 = no change (condition has got worse [worst outcome]), 10 = a great deal better, and a considerable improvement that has made all the difference.
measure: Change in Optimism
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Life Orientation Test (LOT-R). 5-point Likert scale: 0 = strongly disagree, 4 = strongly agree (worse outcome is a function of the question).
measure: Change in Emotion Regulation.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Emotion Regulation Questionnaire (ERQ). 7-point Likert scale: 1 = strongly disagree, 7 = strongly agree (worse outcome is a function of the question).
measure: Change in Mindfulness.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Mindful Attention Awareness Scale (MAAS). 7-point Likert scale: 0 = almost always (worse outcome), 7 = almost never.
measure: Change in Pain Coping Strategies.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Coping Strategies Questionnaire (CSQ). 7-point Likert scale: 0 = never do, 7 = always do that (worse outcome is a function of the question).
measure: Change in Structural (Brain) MRI.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Acquire 2 structural MRI brain scans (before and after treatment) to measure brain gray matter changes due to treatment.
measure: Change in Resting-State Functional MRI.
time frame: from pre-treatment to post-treatment = 8 weeks.
description: Acquire 2 functional MRI brain scans (before and after treatment), during which the participants will rest, to measure functional brain changes due to treatment.
measure: Change in Diffusion Tensor Imaging (DTI) MRI.
time frame: Change from pre-treatment to post-treatment = 8 weeks.
description: Acquire 2 DTI MRI scans (before and after treatment) to measure brain white matter changes due to treatment.
measure: Assessment of Usability of VR Device.
time frame: At the end of the Therapy Period (post-treatment; approx. 10 weeks into study).
description: Questionnaire with 10 questions on usability of the VR device; 5-point Likert scale: 1 = strongly disagree, 5 = strongly agree (worse outcome is a function of the question).
measure: Assessment of Sense of Presence in the VR Environment.
time frame: At the end of the Therapy Period (post-treatment; approx. 10 weeks into study).
description: Questionnaire with 14 questions about the participant's sense of presence in the virtual environment - based on IGP Presence Questionnaire; 5-point Likert scale: 1 = fully disagree, 5 = fully agree (worse outcome is a function of the question).
measure: Assessment of Sense of Embodiment in the VR Environment.
time frame: At the end of the Therapy Period (post-treatment; approx. 10 weeks into study)
description: Questionnaire with 10 questions about the participant's sense of embodiment in the virtual reality environment - based on the Gonzalez-Franko Embodiment Questionnaire; 7-point Likert scale from -3 = strongly disagree to +3 = strongly agree (worse outcome is a function of the question).
arm group label: Therapy Group
arm group type: Experimental
description: Therapy Group participants start the treatment period with three 1 ½ hour introductory sessions:
An education session on the science behind chronic pain and a basic overview of the VR therapy.
A session to customize the VR experience to match the participant's own pain experience.
A training session on the use of the VR hardware and software.
Upon completion, participants begin using the VR therapy app at home once a day, 5 times a week (minimum), for a total of 8 weeks. The VR app contains different training exercises. A workbook provides a schedule and background on each of the training sessions.
Therapy Group participants may continue their other pain treatment regimes, and are asked to notify the research team of any changes.
arm group label: Standard of Care (SOC) Group
arm group type: No Intervention
description: The SOC Group (no-intervention) completes a daily pain survey. SOC Group participants are asked to maintain their pain treatment regimes, and are asked to notify the research team of any changes.
intervention type: Device
intervention name: Virtual Reality Therapy for Chronic Pain
description: A 1 1/2 PowerPoint-based education session on the science behind chronic pain and a basic overview of the VR therapy
Virtual Reality Therapy: a virtual reality therapy consisting of different psychological training exercises
arm group label: Therapy Group
other name: Virtual Reality Neuropsychological Therapy (VRNT)
criteria: 
gender: All
minimum age: 21 Years
maximum age: 70 Years
healthy volunteers: No
last name: Marta Ceko, Ph.D.
role: Principal Investigator
affiliation: University of Colorado, Boulder
last name: Lynn Webster, MD
role: Principal Investigator
affiliation: CognifiSense Inc.
last name: Tassilo Baeuerle
role: Principal Investigator
affiliation: CognifiSense Inc.
facility: 
country: United States
citation: Cherkin DC, Sherman KJ, Balderson BH, Cook AJ, Anderson ML, Hawkes RJ, Hansen KE, Turner JA. Effect of Mindfulness-Based Stress Reduction vs Cognitive Behavioral Therapy or Usual Care on Back Pain and Functional Limitations in Adults With Chronic Low Back Pain: A Randomized Clinical Trial. JAMA. 2016 Mar 22-29;315(12):1240-9. doi: 10.1001/jama.2016.2323.
PMID: 27002445
responsible party type: Sponsor
mesh term: Back Pain
mesh term: Chronic Pain
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 