xml: <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/NCT06038240</url>
    </required_header>
    <id_info>
      <org_study_id>HSR230005</org_study_id>
      <nct_id>NCT06038240</nct_id>
    </id_info>
    <brief_title>Optimizing Pain Self-Management in Total Knee Arthroplasty</brief_title>
    <official_title>Optimizing Pain Self-Management in Total Knee Arthroplasty</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Virginia</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Virginia</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to investigate the efficacy of a positive affect enhancing&#xD;
        intervention designed to reduce pain and augment reward system function in knee&#xD;
        osteoarthritis (KOA) patients undergoing total knee arthroplasty (TKA). The scientific&#xD;
        premise is that patient use of a positive emotion generative practice - savoring meditation,&#xD;
        which has been demonstrated to reduce pain in experimental laboratory settings, enhanced with&#xD;
        a pain neuroscience education component about reward system dysfunction as a chronic pain&#xD;
        mechanism - is optimally suited to reduce postsurgical pain and augment reward system&#xD;
        functioning relative to a Pain Self-Management and Education (PSME) condition. We will&#xD;
        randomize 150 patients with KOA undergoing unilateral TKA to a brief, 4-session (20-30&#xD;
        minutes each) course of Savoring Meditation (SM; n = 75) or PSME (n = 75) delivered remotely&#xD;
        by trained interventionists in a one-on-one format. We will assess pain and as well as&#xD;
        pain-related risk and protective factors both via questionnaire and via weeklong ecological&#xD;
        momentary assessment (EMA) data bursts on the following schedule: baseline, post-surgery, and&#xD;
        3-month follow-up. In addition, participants will attend laboratory testing sessions at&#xD;
        baseline and 6-weeks post-surgery, during which affective pain modulation and&#xD;
        electroencephalographic (EEG) brain biomarkers associated with pain and affect will be&#xD;
        recorded. Participants in SM be encouraged to practice their savoring for 5 minutes/day&#xD;
        during the week following surgery, as well as to use it to manage pain flares in a&#xD;
        self-directed manner.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Total knee arthroplasty (TKA) is an increasingly utilized, end-stage, cost-effective&#xD;
        treatment for knee osteoarthritis (OA), one of the leading causes of disability worldwide&#xD;
        (Felson, 2009) whose hallmark symptoms include pain, stiffness, limited range of motion, and&#xD;
        physical mobility limitations (NIAMS, 2019). The mechanisms of pain in OA, like most chronic&#xD;
        pain conditions, are complex, multifaceted, and involve both central and peripheral&#xD;
        sensitization (Bharde et al., 2021), as well as reward system dysfunction (Wang &amp; Ni, 2022).&#xD;
        Despite its overall efficacy, a significant portion of patients with TKA (10-34%) continue to&#xD;
        experience painful joints following the procedure (Beswick et al., 2012), while an estimated&#xD;
        20% are dissatisfied with the outcome of their procedure (Bourne et al., 2010; Springer &amp;&#xD;
        Sotile, 2020). Further, an estimated 20% experience significant post-operative psychological&#xD;
        distress in the months following surgery, which longitudinally predicts poorer functional&#xD;
        outcomes (Cremeans-Smith et al., 2011). TKA on average fails to improve pain and function to&#xD;
        a level comparable to the general population, or to the level achieved by other joint&#xD;
        replacement procedures (i.e., hip arthroplasty) (Jones et al., 2007; Linsell et al., 2006).&#xD;
        These limitations highlight an urgent need to investigate safe and scalable strategies to&#xD;
        improve TKA outcomes.&#xD;
  &#xD;
        Psychosocial processes have a clinically meaningful role in shaping TKA outcomes.&#xD;
        Well-established presurgical cognitive and affective risk factors include pain&#xD;
        catastrophizing (Lewis et al., 2015; M. Sullivan et al., 2011), kinesiophobia (Filardo et&#xD;
        al., 2017), poor outcome expectations (M. Sullivan et al., 2011; Tilbury et al., 2018) and&#xD;
        reward system dysfunction (Lewis et al., 2015). Meanwhile, emerging research suggests that&#xD;
        positive, resilience-related factors such as positive affect, vitality, vigor, social&#xD;
        support, self-efficacy, and global, trait-like resilience (Nwankwo et al., 2021) predict more&#xD;
        favorable TKA outcomes (Cremeans-Smith et al., 2022; Edwards et al., 2022).&#xD;
  &#xD;
        Major Gap in Knowledge&#xD;
  &#xD;
        Despite known, modifiable psychological risk and resilience factors known to impact TKA&#xD;
        outcomes, only recently have psychosocial processes in TKA been targeted in clinical trials.&#xD;
        We are aware of a handful of investigations which have variously employed psychoeducation,&#xD;
        guided imagery, motivational interviewing, and cognitive-behavioral approaches, which have&#xD;
        demonstrated modest to poor efficacy in impacting postsurgical pain and function (Bay et al.,&#xD;
        2018). Pain neuroscience education (PNE) is a relatively recent psychosocial intervention&#xD;
        approach to chronic pain that educates patients on the modern neuroscientific understanding&#xD;
        of mechanisms (e.g., central and peripheral sensitization), whose efficacy appears to be&#xD;
        optimized when combined with an additional active treatment (e.g., physical therapy) informed&#xD;
        by the patent's reconceptualization of pain (away from biomedical or biomechanical&#xD;
        understanding and towards a modern neuroscientific understanding) achieved through PNE&#xD;
        (Moseley &amp; Butler, 2015; J. A. Watson et al., 2019). Initial studies on PNE alone in TKA&#xD;
        patients show a favorable effect on patient satisfaction with the TKA procedure (Louw et al.,&#xD;
        2019) and psychosocial risk factors including pain catastrophizing and kinesiophobia (Lluch&#xD;
        et al., 2018) but no effect on pain or function.&#xD;
  &#xD;
        How Proposed Work Will Fill the Gaps&#xD;
  &#xD;
        The present study will address major gaps in knowledge by testing a novel prophylactic&#xD;
        psychological intervention for TKA patients that targets reward system dysfunction, a central&#xD;
        driver of chronic pain states. Specifically, we will test a novel Savoring Meditation (SM)&#xD;
        intervention, which teaches patients how to augment positive affective functioning via&#xD;
        meditating on a positive autobiographical memory. In addition, using a pain neuroscience&#xD;
        education framework, SM will also educate participants on the neurophysiological basis for&#xD;
        engaging in savoring meditation. Specifically, we will educate patients about the reward&#xD;
        system in the brain, and how deficits in reward system functioning serve to maintain pain.&#xD;
        Subsequently, we will explain to patients that savoring meditation has been empirically shown&#xD;
        and is optimally suited to reduce pain vis-a-vis augmented reward system functioning.&#xD;
        Patients randomized to SM will engage in 4 sessions of SM with a trained interventionist.&#xD;
        They will be encouraged to use their SM skills in the postsurgical period to manage pain. We&#xD;
        will compare the efficacy of SM to a Pain Self-Management and Education (PSME) condition,&#xD;
        wherein patients will learn about biological, psychological, and social drivers of pain. The&#xD;
        PSME condition will control for therapeutic alliance and treatment expectancies. We&#xD;
        hypothesize that patients who undergo 4 sessions of SM will demonstrate reduced clinical pain&#xD;
        and prescription opioid use across major assessment timepoints (post-treatment, 6-weeks, and&#xD;
        3-months), relative to PSME. Reward system function measured via self-report, affective pain&#xD;
        modulation task performance, and electroencephalographic (EEG) based biomarkers will be&#xD;
        investigated as a secondary outcome.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2027</completion_date>
    <primary_completion_date type="Anticipated">September 2026</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>Double (Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Clinical Pain</measure>
      <time_frame>Baseline to 3 months post-surgery</time_frame>
      <description>Average pain intensity on numeric rating scale, aggregated across Ecological Momentary Assessment observations</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Opioid Use</measure>
      <time_frame>Baseline to 3-months post-surgery</time_frame>
      <description>Morphine Equivalent Units per day, as assessed with Ecological Momentary Assessment</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Koos Jr</measure>
      <time_frame>Baseline to 3 months post-surgery</time_frame>
      <description>Affective Pain Modulation Task Performance</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Positive Emotions</measure>
      <time_frame>Baseline to 3-months post-surgery</time_frame>
      <description>PANAS-X</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anhedonia</measure>
      <time_frame>Baseline to 3-months post-surgery</time_frame>
      <description>SHAPS</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">150</enrollment>
    <condition>Osteo Arthritis Knee</condition>
    <condition>Knee Pain Chronic</condition>
    <condition>Surgery</condition>
    <arm_group>
      <arm_group_label>Savoring Meditation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>A 4-session meditation intervention in which participants are trained to generate positive emotional states and focus their awareness on those states throughout the meditation.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Pain Self-Management and Education</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Education Control</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Savoring Meditation</intervention_name>
      <description>Participants will learn about pain neuroscience and will learn/practice a positive emotion generative practice (Savoring Meditation).</description>
      <arm_group_label>Savoring Meditation</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Pain Self-Management and Education</intervention_name>
      <description>Participants will learn about the biopsychosocial drivers of chronic pain.</description>
      <arm_group_label>Pain Self-Management and Education</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  18-85 years old.&#xD;
  &#xD;
            -  Have a physician-confirmed treatment plan to undergo unilateral TKA along with&#xD;
               physician-confirmed knee osteoarthritis diagnosis.&#xD;
  &#xD;
            -  Willingness and ability to comply with scheduled sessions and study procedures&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Member of a vulnerable population including pregnant women, children, prisoners,&#xD;
               cognitively impaired, and non-English-speaking subjects.&#xD;
  &#xD;
            -  Current unstable, severe medical comorbidity.&#xD;
  &#xD;
            -  Current severe psychiatric comorbidity (e.g., schizophrenia, psychosis, or other&#xD;
               unstable psychiatric disorder).&#xD;
  &#xD;
            -  Current severe alcohol or substance use disorder.&#xD;
  &#xD;
            -  Weekly or more frequent use of opioids in the past 30 days (other than tramadol and/or&#xD;
               codeine) for therapeutic or non-therapeutic purposes.&#xD;
  &#xD;
            -  Other surgery of the affected knee in the last 6 months.&#xD;
  &#xD;
            -  Previous TKA.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Patrick Finan, PhD</last_name>
      <phone>4349249514</phone>
      <email>tpx4xe@uvahealth.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>Fontaine Research Park</name>
        <address>
          <city>Charlottesville</city>
          <state>Virginia</state>
          <zip>22903</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Patrick Finan, PhD</last_name>
        <email>tpx4xe@uvahealth.org</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 7, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Virginia</investigator_affiliation>
      <investigator_full_name>Patrick Finan, PhD</investigator_full_name>
      <investigator_title>Harold Carron Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Osteoarthritis</mesh_term>
      <mesh_term>Osteoarthritis, Knee</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Deidentified data will be shared upon reasonable request from other researchers, and after a data use agreement has been executed between institutions.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>Data will become available after the study is complete and the primary outcomes manuscript has been published.</ipd_time_frame>
      <ipd_access_criteria>Access will be granted after a Data Use Agreement has been executed.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06038240
  org study id: HSR230005
  nct id: NCT06038240
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this study is to investigate the efficacy of a positive affect enhancing
        intervention designed to reduce pain and augment reward system function in knee
        osteoarthritis (KOA) patients undergoing total knee arthroplasty (TKA). The scientific
        premise is that patient use of a positive emotion generative practice - savoring meditation,
        which has been demonstrated to reduce pain in experimental laboratory settings, enhanced with
        a pain neuroscience education component about reward system dysfunction as a chronic pain
        mechanism - is optimally suited to reduce postsurgical pain and augment reward system
        functioning relative to a Pain Self-Management and Education (PSME) condition. We will
        randomize 150 patients with KOA undergoing unilateral TKA to a brief, 4-session (20-30
        minutes each) course of Savoring Meditation (SM; n = 75) or PSME (n = 75) delivered remotely
        by trained interventionists in a one-on-one format. We will assess pain and as well as
        pain-related risk and protective factors both via questionnaire and via weeklong ecological
        momentary assessment (EMA) data bursts on the following schedule: baseline, post-surgery, and
        3-month follow-up. In addition, participants will attend laboratory testing sessions at
        baseline and 6-weeks post-surgery, during which affective pain modulation and
        electroencephalographic (EEG) brain biomarkers associated with pain and affect will be
        recorded. Participants in SM be encouraged to practice their savoring for 5 minutes/day
        during the week following surgery, as well as to use it to manage pain flares in a
        self-directed manner.
  Total knee arthroplasty (TKA) is an increasingly utilized, end-stage, cost-effective
        treatment for knee osteoarthritis (OA), one of the leading causes of disability worldwide
        (Felson, 2009) whose hallmark symptoms include pain, stiffness, limited range of motion, and
        physical mobility limitations (NIAMS, 2019). The mechanisms of pain in OA, like most chronic
        pain conditions, are complex, multifaceted, and involve both central and peripheral
        sensitization (Bharde et al., 2021), as well as reward system dysfunction (Wang & Ni, 2022).
        Despite its overall efficacy, a significant portion of patients with TKA (10-34%) continue to
        experience painful joints following the procedure (Beswick et al., 2012), while an estimated
        20% are dissatisfied with the outcome of their procedure (Bourne et al., 2010; Springer &
        Sotile, 2020). Further, an estimated 20% experience significant post-operative psychological
        distress in the months following surgery, which longitudinally predicts poorer functional
        outcomes (Cremeans-Smith et al., 2011). TKA on average fails to improve pain and function to
        a level comparable to the general population, or to the level achieved by other joint
        replacement procedures (i.e., hip arthroplasty) (Jones et al., 2007; Linsell et al., 2006).
        These limitations highlight an urgent need to investigate safe and scalable strategies to
        improve TKA outcomes.
  
        Psychosocial processes have a clinically meaningful role in shaping TKA outcomes.
        Well-established presurgical cognitive and affective risk factors include pain
        catastrophizing (Lewis et al., 2015; M. Sullivan et al., 2011), kinesiophobia (Filardo et
        al., 2017), poor outcome expectations (M. Sullivan et al., 2011; Tilbury et al., 2018) and
        reward system dysfunction (Lewis et al., 2015). Meanwhile, emerging research suggests that
        positive, resilience-related factors such as positive affect, vitality, vigor, social
        support, self-efficacy, and global, trait-like resilience (Nwankwo et al., 2021) predict more
        favorable TKA outcomes (Cremeans-Smith et al., 2022; Edwards et al., 2022).
  
        Major Gap in Knowledge
  
        Despite known, modifiable psychological risk and resilience factors known to impact TKA
        outcomes, only recently have psychosocial processes in TKA been targeted in clinical trials.
        We are aware of a handful of investigations which have variously employed psychoeducation,
        guided imagery, motivational interviewing, and cognitive-behavioral approaches, which have
        demonstrated modest to poor efficacy in impacting postsurgical pain and function (Bay et al.,
        2018). Pain neuroscience education (PNE) is a relatively recent psychosocial intervention
        approach to chronic pain that educates patients on the modern neuroscientific understanding
        of mechanisms (e.g., central and peripheral sensitization), whose efficacy appears to be
        optimized when combined with an additional active treatment (e.g., physical therapy) informed
        by the patent's reconceptualization of pain (away from biomedical or biomechanical
        understanding and towards a modern neuroscientific understanding) achieved through PNE
        (Moseley & Butler, 2015; J. A. Watson et al., 2019). Initial studies on PNE alone in TKA
        patients show a favorable effect on patient satisfaction with the TKA procedure (Louw et al.,
        2019) and psychosocial risk factors including pain catastrophizing and kinesiophobia (Lluch
        et al., 2018) but no effect on pain or function.
  
        How Proposed Work Will Fill the Gaps
  
        The present study will address major gaps in knowledge by testing a novel prophylactic
        psychological intervention for TKA patients that targets reward system dysfunction, a central
        driver of chronic pain states. Specifically, we will test a novel Savoring Meditation (SM)
        intervention, which teaches patients how to augment positive affective functioning via
        meditating on a positive autobiographical memory. In addition, using a pain neuroscience
        education framework, SM will also educate participants on the neurophysiological basis for
        engaging in savoring meditation. Specifically, we will educate patients about the reward
        system in the brain, and how deficits in reward system functioning serve to maintain pain.
        Subsequently, we will explain to patients that savoring meditation has been empirically shown
        and is optimally suited to reduce pain vis-a-vis augmented reward system functioning.
        Patients randomized to SM will engage in 4 sessions of SM with a trained interventionist.
        They will be encouraged to use their SM skills in the postsurgical period to manage pain. We
        will compare the efficacy of SM to a Pain Self-Management and Education (PSME) condition,
        wherein patients will learn about biological, psychological, and social drivers of pain. The
        PSME condition will control for therapeutic alliance and treatment expectancies. We
        hypothesize that patients who undergo 4 sessions of SM will demonstrate reduced clinical pain
        and prescription opioid use across major assessment timepoints (post-treatment, 6-weeks, and
        3-months), relative to PSME. Reward system function measured via self-report, affective pain
        modulation task performance, and electroencephalographic (EEG) based biomarkers will be
        investigated as a secondary outcome.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Investigator, Outcomes Assessor)
  measure: Clinical Pain
  time frame: Baseline to 3 months post-surgery
  description: Average pain intensity on numeric rating scale, aggregated across Ecological Momentary Assessment observations
  measure: Opioid Use
  time frame: Baseline to 3-months post-surgery
  description: Morphine Equivalent Units per day, as assessed with Ecological Momentary Assessment
  measure: Koos Jr
  time frame: Baseline to 3 months post-surgery
  description: Affective Pain Modulation Task Performance
  measure: Positive Emotions
  time frame: Baseline to 3-months post-surgery
  description: PANAS-X
  measure: Anhedonia
  time frame: Baseline to 3-months post-surgery
  description: SHAPS
  arm group label: Savoring Meditation
  arm group type: Experimental
  description: A 4-session meditation intervention in which participants are trained to generate positive emotional states and focus their awareness on those states throughout the meditation.
  arm group label: Pain Self-Management and Education
  arm group type: Other
  description: Education Control
  intervention type: Behavioral
  intervention name: Savoring Meditation
  description: Participants will learn about pain neuroscience and will learn/practice a positive emotion generative practice (Savoring Meditation).
  arm group label: Savoring Meditation
  intervention type: Behavioral
  intervention name: Pain Self-Management and Education
  description: Participants will learn about the biopsychosocial drivers of chronic pain.
  arm group label: Pain Self-Management and Education
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 85 Years
  healthy volunteers: No
  last name: Patrick Finan, PhD
  phone: 4349249514
  email: tpx4xe@uvahealth.org
  facility: 
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: University of Virginia
  investigator full name: Patrick Finan, PhD
  investigator title: Harold Carron Professor
  mesh term: Osteoarthritis
  mesh term: Osteoarthritis, Knee
  sharing ipd: Yes
  ipd description: Deidentified data will be shared upon reasonable request from other researchers, and after a data use agreement has been executed between institutions.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Analytic Code
  ipd time frame: Data will become available after the study is complete and the primary outcomes manuscript has been published.
  ipd access criteria: Access will be granted after a Data Use Agreement has been executed.