<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/NCT04504812</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00238678</org_study_id>
    <secondary_id>1UG3AR077360-01</secondary_id>
    <nct_id>NCT04504812</nct_id>
  </id_info>
  <brief_title>A Sequenced Strategy for Improving Outcomes in People With Knee Osteoarthritis Pain</brief_title>
  <acronym>SKOAP</acronym>
  <official_title>A Sequenced Strategy for Improving Outcomes in People With Knee Osteoarthritis Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      There is an urgent public health need to reduce reliance on opioids for effective long-term&#xD;
      pain management, particularly in knee osteoarthritis (KOA). This effectiveness trial will&#xD;
      compare commonly recommended treatments to reduce pain and functional limitations in&#xD;
      KOA.These results will lead to improved patient selection for treatment and inform evidence&#xD;
      based guidelines by offering well-tested, effective, non-surgical alternatives.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Knee osteoarthritis (KOA) is one of the leading causes of chronic pain and disability&#xD;
      worldwide, affecting over 30% of older adults. It represents a major global health and&#xD;
      economic burden to individuals and society. The rates of KOA have more than doubled in the&#xD;
      past 70 years and continue to grow sharply, given increases in life expectancy and population&#xD;
      body mass index (BMI). Surgery is often employed to treat KOA, but it is associated with a&#xD;
      high rate of persistent pain, and is not a permanent solution. Numerous nonsurgical therapies&#xD;
      have been advocated to treat pain in patients with KOA yet are not often used in clinical&#xD;
      care. The limited pain relief and functional improvement seen in a subset of knee OA&#xD;
      sufferers has led to a high rate of opioid use and disability in this population. The&#xD;
      overarching goal of this study is to conduct a sequential parallel group randomized&#xD;
      controlled trial (RCT) to evaluate the comparative effectiveness of conservative behavioral&#xD;
      and non-opioid pharmacological treatments (Phase 1) and, among those that indicate interest&#xD;
      in obtaining further treatment and those not eligible for conservative treatment, the&#xD;
      benefits of procedural interventions (Phase 2). This study will also evaluate whether&#xD;
      clinical and psychosocial phenotypes predict short- and longer-term treatment response. The&#xD;
      results of this study will examine the effectiveness of each tested intervention and provide&#xD;
      meaningful information regarding effectiveness across key subgroups of participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 1, 2021</start_date>
  <completion_date type="Anticipated">August 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">April 1, 2024</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Using a stepped care model, Phase 1 participants will be randomly assigned to minimally invasive treatments, including best practices, best practices plus duloxetine, and best practices plus duloxetine combined with a web-based pain coping skills training program. Those who note interest in additional treatment following completion of Phase 1, as well as those that are not eligible for Phase 1 treatment, will be randomly assigned to more aggressive procedures: intra-articular hyaluronic acid, steroid and local anesthetic injection, or a nerve procedure that would either include a long acting block or nerve ablation.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Individuals randomized to a nerve procedure will be blinded to whether they have a long acting block or nerve ablation.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Pain Intensity as assessed by the Modified 4-item BPI Pain Scale</measure>
    <time_frame>Baseline and 8 weeks post-treatment for Phase 1; Baseline and 12 weeks post-treatment for Phase 2</time_frame>
    <description>The Modified 4-item BPI Pain scale consists of 3 items from BPI Pain Intensity and 1 item from BPI Pain Interference. This is a continuous measure that will be calculated as the average of worst, average, current knee pain, and pain upon walking.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Pain Interference as assessed by the BPI</measure>
    <time_frame>Baseline and 8 weeks post-treatment for Phase 1; Baseline and 12 weeks post-treatment for Phase 2</time_frame>
    <description>The BPI Pain Interference domain assesses self-reported consequences of pain on relevant aspects of one's life. The BPI measures how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. BPI pain interference is typically scored as the mean of the seven interference items. BPI Interference ranges from 0-10 with higher scores reflecting greater pain interference in activities of daily living.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Physical Functioning as assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS)</measure>
    <time_frame>Baseline and 8 weeks post-treatment for Phase 1; Baseline and 12 weeks post-treatment for Phase 2</time_frame>
    <description>The KOOS evaluates function for participants with osteoarthritis of the knee that is related to injury and degeneration. The KOOS short form includes 12 items and measures pain, functional limitation and quality of life. Physical functioning questions cover everyday activities such as rising from sitting, standing getting in and out of the car and twisting/pivoting on the knee. Scores range from 0-100 with lower scores indicating worse knee symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global impression of Change (PGIC)</measure>
    <time_frame>At 8 weeks post-treatment for Phase 1; At 12 weeks post-treatment for Phase 2</time_frame>
    <description>The PGIC scale evaluates all aspects of participants' health and assesses if there has been an improvement or decline in clinical status. It is a 7-item scale that ranges between &quot;a great deal worse&quot; to &quot;a great deal better.&quot; Higher scores reflect greater improvement in clinical status.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">2700</enrollment>
  <condition>Knee Osteoarthrosis</condition>
  <arm_group>
    <arm_group_label>Phase 1: Best Practices</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive an intervention from the best practices.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1: Best Practices + Duloxetine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive Duloxetine in addition to an intervention from the best practices.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1:Best Practices + Duloxetine + Pain coping skills</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive Duloxetine and pain coping skills training in addition to an intervention from the best practices.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2: Intra-Articular Injection (HA+)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive an intra-articular injection of hyaluronic acid mixed with steroid and bupivacaine.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2: Nerve Procedure: Long Acting Blocks</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive a nerve blocking procedure, long-acting local anesthetic, and steroid injection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2: Nerve Procedure: Nerve Ablation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive a nerve ablation procedure and steroid injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Duloxetine</intervention_name>
    <description>Duloxetine is a drug that is used to improve pain and function in people with knee osteoarthritis (KOA). Duloxetine is approved by the Food and Drug Administration (FDA) for the treatment of depression, anxiety disorder, fibromyalgia, and joint pain. It will be titrated up from 20 or 30mg according to a schedule provided by a study provider.</description>
    <arm_group_label>Phase 1: Best Practices + Duloxetine</arm_group_label>
    <arm_group_label>Phase 1:Best Practices + Duloxetine + Pain coping skills</arm_group_label>
    <other_name>Cymbalta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Intra-Articular Injection</intervention_name>
    <description>Intra-Articular Injection is an injection of 3-6 milliliter (mL) hyaluronic acid (HA) mixed with 1mL depo methylprednisolone (a steroid) and 2mL 0.5% bupivacaine (an anesthetic) into the knee.</description>
    <arm_group_label>Phase 2: Intra-Articular Injection (HA+)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Nerve Procedure with long acting blocks</intervention_name>
    <description>People assigned to receive this will have 1mL of a long-acting local anesthetic (a.k.a. liposomal bupivacaine or EXPAREL) and steroid injected into the knee.</description>
    <arm_group_label>Phase 2: Nerve Procedure: Long Acting Blocks</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Nerve Procedure with nerve ablation</intervention_name>
    <description>People assigned to receive this will have heat applied to destroy the nerve signaling pain in the knee. Steroid will be administered after the procedure to reduce the risk of neuritis.</description>
    <arm_group_label>Phase 2: Nerve Procedure: Nerve Ablation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Pain Coping Skills Training</intervention_name>
    <description>Participants will be provided with a written manual that includes login information for the pain coping skills training website. They will be expected to log into the system weekly, work through the modules, and participate in skills practice. This intervention will be conducted in combination with best practices and duloxetine.</description>
    <arm_group_label>Phase 1:Best Practices + Duloxetine + Pain coping skills</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Best Practices</intervention_name>
    <description>Best Practice includes treatments that experts recommend for knee arthritis pain. Best Practice can include topical or oral pain relievers, a structured exercise program, and weight management if BMI is over 30. Other non-invasive treatments such as acupuncture and yoga are also included.</description>
    <arm_group_label>Phase 1: Best Practices</arm_group_label>
    <arm_group_label>Phase 1: Best Practices + Duloxetine</arm_group_label>
    <arm_group_label>Phase 1:Best Practices + Duloxetine + Pain coping skills</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Meets American College of Rheumatology Classification criteria for knee osteoarthritis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any inability to complete study procedures, including, but not limited to inadequate&#xD;
             resources to mitigate low English language literacy&#xD;
&#xD;
          -  Unstable medical condition that presents as an absolute or relative contraindication&#xD;
             for participation (e.g., unstable angina, poorly controlled diabetes mellitus, end&#xD;
             stage renal failure, automated implantable cardioverter-defibrillator that cannot be&#xD;
             disabled before RFA).&#xD;
&#xD;
          -  Severe untreated bleeding disorder (anticoagulants may be continued during phase II&#xD;
             treatments in most patients)&#xD;
&#xD;
          -  Severe vision or hearing impairment or serious cognitive impairment that could&#xD;
             interfere with consent or outcome assessment&#xD;
&#xD;
          -  Poorly controlled serious psychiatric condition&#xD;
&#xD;
          -  Active substance abuse&#xD;
&#xD;
          -  Scheduled joint replacement on the affected knee&#xD;
&#xD;
          -  History of unilateral total knee arthroplasty (TKA) with complaints of KOA pain&#xD;
             limited to the operated knee&#xD;
&#xD;
          -  Ulcers or an open wound in the region of the index knee&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven Cohen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Claudia Campbell, PhD</last_name>
    <phone>888-304-0711</phone>
    <email>ccampb41@jhmi.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Alabama</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <email>shannagraves@uabmc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Arkansas</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>501-398-8622</phone>
      <email>tricoordinators@uams.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of California Davis</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>916-416-5887</phone>
      <email>cqthai@ucdavis.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of California San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>858-822-3108</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>734-476-1146</phone>
      <email>andrew.clauw@cuanschutz.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32608</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>352-273-8911</phone>
      <email>agunnett@anest.ufl.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Florida</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>904-953-4529</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>404-251-0759</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>312-695-0915</phone>
      <email>jordan.wood1@northwestern.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Iowa</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>319-356-1722</phone>
      <email>chimenti-lab@healthcare.uiowa.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <email>SKOAPstudy@jhmi.edu</email>
    </contact>
    <contact_backup>
      <phone>(443) 961-7246</phone>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02199</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>617-732-9463</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <email>skoap@umn.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cornell University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10019</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>212-746-9419</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of North Carolina</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>919-966-5495</phone>
      <email>bradley_lauck@med.unc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Wake Forest University</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27517</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>336-716-8791</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Hospitals</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <email>Rheumresearch@uhhospitals.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>503-494-2180</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>615-313-7005</phone>
      <email>denise.de.la.torre@vumc.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84108</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>801-587-1436</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Virginia</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>434-409-1058</phone>
      <email>MEB2W@hscmail.mcc.virginia.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98185</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Coordinator</last_name>
      <phone>206-221-5572</phone>
      <email>abbychiu@uw.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>August 5, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>July 11, 2023</last_update_submitted>
  <last_update_submitted_qc>July 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Duloxetine Hydrochloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>After last subject enrollment and all follow up procedures have been completed, the Helping to End Addiction Long-Term (HEAL) Pain Management Effectiveness Research Network Data Coordinating Center at the University of Utah will prepare a final study database for the trial, which will then be used for statistical analyses and publication of findings from the trial.The Trial will provide a resource of data concerning methods for managing pain and reducing opioid addiction, and the Data Coordinating Center (DCC) will produce a database that can be used by non- Effectiveness Research Network (ERN) investigators.The DCC will also prepare a data dictionary that provides a concise definition of every data element included in the database. If specific data elements have idiosyncrasies that might affect interpretation or analysis, this will be discussed in the dictionary document. Data elements that are considered unreliable will be deleted, and this will be noted in the documentation.</ipd_description>
    <ipd_time_frame>These policies are expected to focus primarily on the timing of data release. The investigator's preliminary plan is to release the database (defined below) at the time of publication of the primary manuscript, or within 12 months of last patient procedure, whichever comes first. Implementation of the plan will follow the HEAL Public Access and Data Sharing Policy as outlined at https://heal.nih.gov/about/public-access-data</ipd_time_frame>
    <ipd_access_criteria>Access to the releasable database housed in the NIH-assigned repository will be in accordance with procedures and regulations of the NIH or specific institute. The data coordinating center will not provide any support for investigators using the releasable database.</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <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>March 14, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/12/NCT04504812/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04504812
org study id: IRB00238678
secondary id: 1UG3AR077360-01
nct id: NCT04504812
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
There is an urgent public health need to reduce reliance on opioids for effective long-term
      pain management, particularly in knee osteoarthritis (KOA). This effectiveness trial will
      compare commonly recommended treatments to reduce pain and functional limitations in
      KOA.These results will lead to improved patient selection for treatment and inform evidence
      based guidelines by offering well-tested, effective, non-surgical alternatives.
Knee osteoarthritis (KOA) is one of the leading causes of chronic pain and disability
      worldwide, affecting over 30% of older adults. It represents a major global health and
      economic burden to individuals and society. The rates of KOA have more than doubled in the
      past 70 years and continue to grow sharply, given increases in life expectancy and population
      body mass index (BMI). Surgery is often employed to treat KOA, but it is associated with a
      high rate of persistent pain, and is not a permanent solution. Numerous nonsurgical therapies
      have been advocated to treat pain in patients with KOA yet are not often used in clinical
      care. The limited pain relief and functional improvement seen in a subset of knee OA
      sufferers has led to a high rate of opioid use and disability in this population. The
      overarching goal of this study is to conduct a sequential parallel group randomized
      controlled trial (RCT) to evaluate the comparative effectiveness of conservative behavioral
      and non-opioid pharmacological treatments (Phase 1) and, among those that indicate interest
      in obtaining further treatment and those not eligible for conservative treatment, the
      benefits of procedural interventions (Phase 2). This study will also evaluate whether
      clinical and psychosocial phenotypes predict short- and longer-term treatment response. The
      results of this study will examine the effectiveness of each tested intervention and provide
      meaningful information regarding effectiveness across key subgroups of participants.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Using a stepped care model, Phase 1 participants will be randomly assigned to minimally invasive treatments, including best practices, best practices plus duloxetine, and best practices plus duloxetine combined with a web-based pain coping skills training program. Those who note interest in additional treatment following completion of Phase 1, as well as those that are not eligible for Phase 1 treatment, will be randomly assigned to more aggressive procedures: intra-articular hyaluronic acid, steroid and local anesthetic injection, or a nerve procedure that would either include a long acting block or nerve ablation.
primary purpose: Treatment
masking: Single (Participant)
masking description: Individuals randomized to a nerve procedure will be blinded to whether they have a long acting block or nerve ablation.
measure: Change in Pain Intensity as assessed by the Modified 4-item BPI Pain Scale
time frame: Baseline and 8 weeks post-treatment for Phase 1; Baseline and 12 weeks post-treatment for Phase 2
description: The Modified 4-item BPI Pain scale consists of 3 items from BPI Pain Intensity and 1 item from BPI Pain Interference. This is a continuous measure that will be calculated as the average of worst, average, current knee pain, and pain upon walking.
measure: Change in Pain Interference as assessed by the BPI
time frame: Baseline and 8 weeks post-treatment for Phase 1; Baseline and 12 weeks post-treatment for Phase 2
description: The BPI Pain Interference domain assesses self-reported consequences of pain on relevant aspects of one's life. The BPI measures how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. BPI pain interference is typically scored as the mean of the seven interference items. BPI Interference ranges from 0-10 with higher scores reflecting greater pain interference in activities of daily living.
measure: Change in Physical Functioning as assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS)
time frame: Baseline and 8 weeks post-treatment for Phase 1; Baseline and 12 weeks post-treatment for Phase 2
description: The KOOS evaluates function for participants with osteoarthritis of the knee that is related to injury and degeneration. The KOOS short form includes 12 items and measures pain, functional limitation and quality of life. Physical functioning questions cover everyday activities such as rising from sitting, standing getting in and out of the car and twisting/pivoting on the knee. Scores range from 0-100 with lower scores indicating worse knee symptoms.
measure: Patient Global impression of Change (PGIC)
time frame: At 8 weeks post-treatment for Phase 1; At 12 weeks post-treatment for Phase 2
description: The PGIC scale evaluates all aspects of participants' health and assesses if there has been an improvement or decline in clinical status. It is a 7-item scale that ranges between "a great deal worse" to "a great deal better." Higher scores reflect greater improvement in clinical status.
arm group label: Phase 1: Best Practices
arm group type: Active Comparator
description: Participants will receive an intervention from the best practices.
arm group label: Phase 1: Best Practices + Duloxetine
arm group type: Active Comparator
description: Participants will receive Duloxetine in addition to an intervention from the best practices.
arm group label: Phase 1:Best Practices + Duloxetine + Pain coping skills
arm group type: Active Comparator
description: Participants will receive Duloxetine and pain coping skills training in addition to an intervention from the best practices.
arm group label: Phase 2: Intra-Articular Injection (HA+)
arm group type: Active Comparator
description: Participants will receive an intra-articular injection of hyaluronic acid mixed with steroid and bupivacaine.
arm group label: Phase 2: Nerve Procedure: Long Acting Blocks
arm group type: Active Comparator
description: Participants will receive a nerve blocking procedure, long-acting local anesthetic, and steroid injection.
arm group label: Phase 2: Nerve Procedure: Nerve Ablation
arm group type: Active Comparator
description: Participants will receive a nerve ablation procedure and steroid injection.
intervention type: Drug
intervention name: Duloxetine
description: Duloxetine is a drug that is used to improve pain and function in people with knee osteoarthritis (KOA). Duloxetine is approved by the Food and Drug Administration (FDA) for the treatment of depression, anxiety disorder, fibromyalgia, and joint pain. It will be titrated up from 20 or 30mg according to a schedule provided by a study provider.
arm group label: Phase 1: Best Practices + Duloxetine
arm group label: Phase 1:Best Practices + Duloxetine + Pain coping skills
other name: Cymbalta
intervention type: Combination Product
intervention name: Intra-Articular Injection
description: Intra-Articular Injection is an injection of 3-6 milliliter (mL) hyaluronic acid (HA) mixed with 1mL depo methylprednisolone (a steroid) and 2mL 0.5% bupivacaine (an anesthetic) into the knee.
arm group label: Phase 2: Intra-Articular Injection (HA+)
intervention type: Procedure
intervention name: Nerve Procedure with long acting blocks
description: People assigned to receive this will have 1mL of a long-acting local anesthetic (a.k.a. liposomal bupivacaine or EXPAREL) and steroid injected into the knee.
arm group label: Phase 2: Nerve Procedure: Long Acting Blocks
intervention type: Procedure
intervention name: Nerve Procedure with nerve ablation
description: People assigned to receive this will have heat applied to destroy the nerve signaling pain in the knee. Steroid will be administered after the procedure to reduce the risk of neuritis.
arm group label: Phase 2: Nerve Procedure: Nerve Ablation
intervention type: Behavioral
intervention name: Pain Coping Skills Training
description: Participants will be provided with a written manual that includes login information for the pain coping skills training website. They will be expected to log into the system weekly, work through the modules, and participate in skills practice. This intervention will be conducted in combination with best practices and duloxetine.
arm group label: Phase 1:Best Practices + Duloxetine + Pain coping skills
intervention type: Other
intervention name: Best Practices
description: Best Practice includes treatments that experts recommend for knee arthritis pain. Best Practice can include topical or oral pain relievers, a structured exercise program, and weight management if BMI is over 30. Other non-invasive treatments such as acupuncture and yoga are also included.
arm group label: Phase 1: Best Practices
arm group label: Phase 1: Best Practices + Duloxetine
arm group label: Phase 1:Best Practices + Duloxetine + Pain coping skills
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Steven Cohen, MD
role: Principal Investigator
affiliation: Johns Hopkins University
last name: Claudia Campbell, PhD
phone: 888-304-0711
email: ccampb41@jhmi.edu
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country: United States
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
mesh term: Duloxetine Hydrochloride
sharing ipd: Yes
ipd description: After last subject enrollment and all follow up procedures have been completed, the Helping to End Addiction Long-Term (HEAL) Pain Management Effectiveness Research Network Data Coordinating Center at the University of Utah will prepare a final study database for the trial, which will then be used for statistical analyses and publication of findings from the trial.The Trial will provide a resource of data concerning methods for managing pain and reducing opioid addiction, and the Data Coordinating Center (DCC) will produce a database that can be used by non- Effectiveness Research Network (ERN) investigators.The DCC will also prepare a data dictionary that provides a concise definition of every data element included in the database. If specific data elements have idiosyncrasies that might affect interpretation or analysis, this will be discussed in the dictionary document. Data elements that are considered unreliable will be deleted, and this will be noted in the documentation.
ipd time frame: These policies are expected to focus primarily on the timing of data release. The investigator's preliminary plan is to release the database (defined below) at the time of publication of the primary manuscript, or within 12 months of last patient procedure, whichever comes first. Implementation of the plan will follow the HEAL Public Access and Data Sharing Policy as outlined at https://heal.nih.gov/about/public-access-data
ipd access criteria: Access to the releasable database housed in the NIH-assigned repository will be in accordance with procedures and regulations of the NIH or specific institute. The data coordinating center will not provide any support for investigators using the releasable database.
provided document: 