<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/NCT03304613</url>
  </required_header>
  <id_info>
    <org_study_id>HUM00124722</org_study_id>
    <secondary_id>5R01NR017096-05</secondary_id>
    <nct_id>NCT03304613</nct_id>
  </id_info>
  <brief_title>Resilience Skills Self-Management for Chronic Pain.</brief_title>
  <official_title>Resilience Skills Self-Management for Chronic Pain.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Nursing Research (NINR)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</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 investigators will conduct a randomized controlled trial of an 8-week resilience-enhanced&#xD;
      CBT online self-management program for chronic pain plus usual care (PRISM), standard e-CBT&#xD;
      self-management plus usual care (e-CBT), and usual care alone. Thus, 300 individuals with&#xD;
      chronic pain will undergo a comprehensive pre-intervention assessment that includes a blood&#xD;
      draw (T1). Participants will then be randomized 2:2:1 as follows: e-CBT (n=120), PRISM&#xD;
      (n=120) and usual care (n = 60). Immediately post-intervention (T2) and at 6 months (T3) and&#xD;
      12 months (T4) after that, participants undergo the same in-person assessment including blood&#xD;
      draw. Telomerase activity will be assessed at T1, T2 and T3; and telomere length at T1 and T4&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 16, 2017</start_date>
  <completion_date type="Actual">March 21, 2023</completion_date>
  <primary_completion_date type="Actual">February 28, 2022</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>
    <intervention_model_description>Participants will be randomized 2:2:1 as follows: e-CBT (n=120), PRISM (n=120) and usual care (n = 60).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fibromyalgia Impact Questionnaire-Revised (FIQ-R)</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>The Fibromyalgia Impact Questionnaire-Revised (FIQR) assesses the total spectrum of problems and responses to therapy. The 2009 revised version contains 21 items assessing broad domains such as physical function, overall impact, and a wide range of symptoms. The measure is self-report with a recall period of the past week and requires only several minutes to complete.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Brief Pain Inventory (BPI)</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>The BPI is a 15-item self-report measure that has been validated for use in a wide variety of pain states. The BPI assesses for the presence of pain, pain intensity (i.e., worst, least, average, current) and functional interference from pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pittsburgh Sleep Quality Index (PSQI)</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>The PSQI is a widely used, valid and reliable measure of global sleep quality and sleep-related symptoms.149 The 19-items yield 7 component-scores that reflect common sleep problems such as subjective sleep quality, sleep disturbance and use of sleep medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PROMIS Fatigue-Short Form</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>The PROMIS Fatigue-Short Form consists of 8 items that assess the impact and experience of fatigue in the past week. It uses a 5-point Likert-like scale with response options that range from &quot;Not at all&quot; to &quot;Very much.&quot; A raw score is calculated by summing scores across items then a conversion table is used to calculate T-scores with higher scores indicating greater fatigue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multidimensional Inventory of Subjective Cognitive Impairment (MISCI)</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>The MISCI is a 10-item measure based upon items developed for PROMIS that assesses perceived difficulties within 5 domains: mental clarity, memory, language, executive functioning, and attention/concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective well-being</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>Subjective well-being has at least three components: positive affective appraisal, negative affective appraisal, and life satisfaction. Composite scores for well-being will be calculated using scores obtained on Positive and Negative Affect Schedule (PANAS) and the Satisfaction with Life Scale (SWLS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Catastrophizing Scale (PCS)</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>. Catastrophizing will be measured using the Pain Catastrophizing Scale (PCS).144 The PCS contains 13 statements regarding various beliefs about pain. A total score is obtained by summing the responses to all items.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Health Questionnaire 9-item (PHQ-9):</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>The PHQ-9 is a 9-item multipurpose instrument that has utility for screening, diagnosing, monitoring, and measuring the severity of depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Generalized Anxiety Disorder 7-item (GAD-7)</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>The GAD-7 is a 7-item measure of anxiety. It has good reliability, criterion, construct, and factorial validity. It has a sensitivity of 89% and specificity of 82% for generalized anxiety disorder.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceived Stress Scale (PSS)</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>The 10-item PSS will be used evaluate an individual's assessment of stress. Participants rate stress on a numeric rating scale from 0 to 10 where higher scores reflect higher levels of stress. Total scores range from 0 to 100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Six-Minute Walk Test (6MWT)</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>The 6MWT measures the distance a participant is able to walk over a total of six minutes on a hard, flat surface. Participants are instructed to walk as far as possible, but allowed to self-pace and rest as needed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sit-to-Stand Test</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>Patients are instructed to stand up 5 times from a chair without arms as fast as possible. The test is repeated twice as this improves reliability. Average time is calculated in seconds.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Telomerase activity as measured by the Droplet Digital PCR (ddPCR) method</measure>
    <time_frame>At 8-week assessment point</time_frame>
    <description>The Blackburn lab collaborated with Biorad to develop a highly sensitive, quantitative and high throughput droplet digital PCR (ddPCR) method to measure telomerase activity in unstimulated PBMCs. This new method has over 10-fold increased sensitivity and over 5-fold increased throughput compared to the currently used gel method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Telomere length</measure>
    <time_frame>At 1 year assessment point</time_frame>
    <description>The DNA will then be analyzed for telomere length using a quantitative polymerase chain reaction (PCR) measurement assay adapted from the methods described by Cawthon with modifications by Lin (Co-I).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">300</enrollment>
  <condition>Chronic Spine Pain</condition>
  <condition>Fibromyalgia</condition>
  <arm_group>
    <arm_group_label>Standard Web-based Cognitive Behavioral Therapy (e-CBT)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomized to e-CBT will undergo &quot;Standard Web-based Cognitive Behavioral Therapy (e-CBT) Self-Management Program&quot; and meet with a study medical assistant (MA) for an orientation session. The MA provides an overview of the program, explains the rationale for treatment, and directs them to the FibroGuide website. FibroGuide features the CBT modules that will be used by both groups. Patients will complete one module per week. Materials needed for the 8-week intervention including the instructions for each activity and forms for the written aspects of an activity (worksheets) will be provided in the first visit and available online. The FibroGuide website evolved from the evidence-based website Living Well with Fibromyalgia that has established efficacy for improving functional status and reducing pain.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Resilience-Enhanced web-based CBT Program</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to PRISM will undergo &quot;Promoting Resilience through Innovative Self-Management&quot; (PRISM) and meet with the MA for an orientation session. The MA describes the program, explains the rationale for treatment, and directs them to the FibroGuide and PRISM websites. Materials and worksheets are provided in the first visit and available online. The e-CBT elements retained are the core elements of CBT for pain, while the resilience-based activities capitalize on the best practices for positive activities interventions including having multiple overlapping activities, making favored activities standard practice beyond the study and having a coaching component.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual Care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients randomized to the usual care only group will have no contact with the study MAs. Usual care patients return for the same follow-up assessments (and electronic medical record review) at 8 weeks and at 6 and 12 months. Whereas major surgery including surgeries for pain, are exclusion criteria, spine and pain injections will be permitted.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Web-based Cognitive Behavioral Therapy (e-CBT) Self-Management</intervention_name>
    <description>Already noted.</description>
    <arm_group_label>Standard Web-based Cognitive Behavioral Therapy (e-CBT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Promoting Resilience through Innovative Self-Management</intervention_name>
    <description>Already noted.</description>
    <arm_group_label>Resilience-Enhanced web-based CBT Program</arm_group_label>
    <other_name>PRISM</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primary back or spine pain diagnosis from the Back &amp; Pain Center at University of&#xD;
             Michigan.&#xD;
&#xD;
          -  High scores on the 2011 survey criteria for Fibromyalgia. The survey criteria for FM&#xD;
             consist of an assessment of widespread pain and symptom severity.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Co-morbid autoimmune disorders, including rheumatoid arthritis and systemic lupus&#xD;
             erythematosus.&#xD;
&#xD;
          -  Medical conditions that can impair health status independent of spine pain and FM,&#xD;
             including cardiopulmonary disorders (e.g. CHF, COPD), uncontrolled endocrine or&#xD;
             allergic disorders (e.g., thyroid dysfunction, Type I diabetes), or malignancy within&#xD;
             the preceding 2 years&#xD;
&#xD;
          -  Current psychotic disorder (schizophrenia, etc.), dissociative identity disorder,&#xD;
             untreated bipolar disorder, active suicide risk, or current alcohol / drug dependence.&#xD;
&#xD;
          -  Planned major surgery in the next 12 months;&#xD;
&#xD;
          -  Pregnancy or taking steroid medications&#xD;
&#xD;
          -  Recent pain interventions ≤6 weeks prior to study (e.g., back surgery, epidural&#xD;
             steroid injections) or planned interventions for the study period (e.g., surgery&#xD;
             scheduled). Ongoing physical therapy will be allowed and new physical therapy or&#xD;
             exercise regimen will be addressed during data analysis;&#xD;
&#xD;
          -  Cognitive impairment or dementia (inability to give consent or meaningfully&#xD;
             participate);&#xD;
&#xD;
          -  Pending or recently received (within 1 years) pain-related disability or Workman's&#xD;
             Compensation;&#xD;
&#xD;
          -  Unable to read or fluently converse in English;&#xD;
&#xD;
          -  Planning to move from the area in next 14 months;&#xD;
&#xD;
          -  In the judgment of the PIs the individual would not be able to meaningfully&#xD;
             participant.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Back &amp; Pain Center, University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>October 3, 2017</study_first_submitted>
  <study_first_submitted_qc>October 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 9, 2017</study_first_posted>
  <last_update_submitted>April 3, 2023</last_update_submitted>
  <last_update_submitted_qc>April 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Afton Hassett, Psy.D.</investigator_full_name>
    <investigator_title>Associate Research Scientist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibromyalgia</mesh_term>
    <mesh_term>Chronic Pain</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03304613
org study id: HUM00124722
secondary id: 5R01NR017096-05
nct id: NCT03304613
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The investigators will conduct a randomized controlled trial of an 8-week resilience-enhanced
      CBT online self-management program for chronic pain plus usual care (PRISM), standard e-CBT
      self-management plus usual care (e-CBT), and usual care alone. Thus, 300 individuals with
      chronic pain will undergo a comprehensive pre-intervention assessment that includes a blood
      draw (T1). Participants will then be randomized 2:2:1 as follows: e-CBT (n=120), PRISM
      (n=120) and usual care (n = 60). Immediately post-intervention (T2) and at 6 months (T3) and
      12 months (T4) after that, participants undergo the same in-person assessment including blood
      draw. Telomerase activity will be assessed at T1, T2 and T3; and telomere length at T1 and T4
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be randomized 2:2:1 as follows: e-CBT (n=120), PRISM (n=120) and usual care (n = 60).
primary purpose: Treatment
masking: None (Open Label)
measure: Fibromyalgia Impact Questionnaire-Revised (FIQ-R)
time frame: At 8-week assessment point
description: The Fibromyalgia Impact Questionnaire-Revised (FIQR) assesses the total spectrum of problems and responses to therapy. The 2009 revised version contains 21 items assessing broad domains such as physical function, overall impact, and a wide range of symptoms. The measure is self-report with a recall period of the past week and requires only several minutes to complete.
measure: Brief Pain Inventory (BPI)
time frame: At 8-week assessment point
description: The BPI is a 15-item self-report measure that has been validated for use in a wide variety of pain states. The BPI assesses for the presence of pain, pain intensity (i.e., worst, least, average, current) and functional interference from pain.
measure: Pittsburgh Sleep Quality Index (PSQI)
time frame: At 8-week assessment point
description: The PSQI is a widely used, valid and reliable measure of global sleep quality and sleep-related symptoms.149 The 19-items yield 7 component-scores that reflect common sleep problems such as subjective sleep quality, sleep disturbance and use of sleep medication.
measure: PROMIS Fatigue-Short Form
time frame: At 8-week assessment point
description: The PROMIS Fatigue-Short Form consists of 8 items that assess the impact and experience of fatigue in the past week. It uses a 5-point Likert-like scale with response options that range from "Not at all" to "Very much." A raw score is calculated by summing scores across items then a conversion table is used to calculate T-scores with higher scores indicating greater fatigue.
measure: Multidimensional Inventory of Subjective Cognitive Impairment (MISCI)
time frame: At 8-week assessment point
description: The MISCI is a 10-item measure based upon items developed for PROMIS that assesses perceived difficulties within 5 domains: mental clarity, memory, language, executive functioning, and attention/concentration.
measure: Subjective well-being
time frame: At 8-week assessment point
description: Subjective well-being has at least three components: positive affective appraisal, negative affective appraisal, and life satisfaction. Composite scores for well-being will be calculated using scores obtained on Positive and Negative Affect Schedule (PANAS) and the Satisfaction with Life Scale (SWLS).
measure: Pain Catastrophizing Scale (PCS)
time frame: At 8-week assessment point
description: . Catastrophizing will be measured using the Pain Catastrophizing Scale (PCS).144 The PCS contains 13 statements regarding various beliefs about pain. A total score is obtained by summing the responses to all items.
measure: Patient Health Questionnaire 9-item (PHQ-9):
time frame: At 8-week assessment point
description: The PHQ-9 is a 9-item multipurpose instrument that has utility for screening, diagnosing, monitoring, and measuring the severity of depression.
measure: Generalized Anxiety Disorder 7-item (GAD-7)
time frame: At 8-week assessment point
description: The GAD-7 is a 7-item measure of anxiety. It has good reliability, criterion, construct, and factorial validity. It has a sensitivity of 89% and specificity of 82% for generalized anxiety disorder.
measure: Perceived Stress Scale (PSS)
time frame: At 8-week assessment point
description: The 10-item PSS will be used evaluate an individual's assessment of stress. Participants rate stress on a numeric rating scale from 0 to 10 where higher scores reflect higher levels of stress. Total scores range from 0 to 100.
measure: Six-Minute Walk Test (6MWT)
time frame: At 8-week assessment point
description: The 6MWT measures the distance a participant is able to walk over a total of six minutes on a hard, flat surface. Participants are instructed to walk as far as possible, but allowed to self-pace and rest as needed.
measure: Sit-to-Stand Test
time frame: At 8-week assessment point
description: Patients are instructed to stand up 5 times from a chair without arms as fast as possible. The test is repeated twice as this improves reliability. Average time is calculated in seconds.
measure: Telomerase activity as measured by the Droplet Digital PCR (ddPCR) method
time frame: At 8-week assessment point
description: The Blackburn lab collaborated with Biorad to develop a highly sensitive, quantitative and high throughput droplet digital PCR (ddPCR) method to measure telomerase activity in unstimulated PBMCs. This new method has over 10-fold increased sensitivity and over 5-fold increased throughput compared to the currently used gel method.
measure: Telomere length
time frame: At 1 year assessment point
description: The DNA will then be analyzed for telomere length using a quantitative polymerase chain reaction (PCR) measurement assay adapted from the methods described by Cawthon with modifications by Lin (Co-I).
arm group label: Standard Web-based Cognitive Behavioral Therapy (e-CBT)
arm group type: Active Comparator
description: Patients randomized to e-CBT will undergo "Standard Web-based Cognitive Behavioral Therapy (e-CBT) Self-Management Program" and meet with a study medical assistant (MA) for an orientation session. The MA provides an overview of the program, explains the rationale for treatment, and directs them to the FibroGuide website. FibroGuide features the CBT modules that will be used by both groups. Patients will complete one module per week. Materials needed for the 8-week intervention including the instructions for each activity and forms for the written aspects of an activity (worksheets) will be provided in the first visit and available online. The FibroGuide website evolved from the evidence-based website Living Well with Fibromyalgia that has established efficacy for improving functional status and reducing pain.
arm group label: Resilience-Enhanced web-based CBT Program
arm group type: Experimental
description: Patients randomized to PRISM will undergo "Promoting Resilience through Innovative Self-Management" (PRISM) and meet with the MA for an orientation session. The MA describes the program, explains the rationale for treatment, and directs them to the FibroGuide and PRISM websites. Materials and worksheets are provided in the first visit and available online. The e-CBT elements retained are the core elements of CBT for pain, while the resilience-based activities capitalize on the best practices for positive activities interventions including having multiple overlapping activities, making favored activities standard practice beyond the study and having a coaching component.
arm group label: Usual Care
arm group type: No Intervention
description: Patients randomized to the usual care only group will have no contact with the study MAs. Usual care patients return for the same follow-up assessments (and electronic medical record review) at 8 weeks and at 6 and 12 months. Whereas major surgery including surgeries for pain, are exclusion criteria, spine and pain injections will be permitted.
intervention type: Behavioral
intervention name: Web-based Cognitive Behavioral Therapy (e-CBT) Self-Management
description: Already noted.
arm group label: Standard Web-based Cognitive Behavioral Therapy (e-CBT)
intervention type: Behavioral
intervention name: Promoting Resilience through Innovative Self-Management
description: Already noted.
arm group label: Resilience-Enhanced web-based CBT Program
other name: PRISM
criteria: 
gender: All
minimum age: 35 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Afton Hassett, Psy.D.
investigator title: Associate Research Scientist
mesh term: Fibromyalgia
mesh term: Chronic Pain