<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/NCT03771430</url>
  </required_header>
  <id_info>
    <org_study_id>MultiKnee Trial</org_study_id>
    <nct_id>NCT03771430</nct_id>
  </id_info>
  <brief_title>A Multidisciplinary Intervention in Total Knee Arthroplasty</brief_title>
  <acronym>MultiKnee</acronym>
  <official_title>A Multidisciplinary Intervention in Total Knee Arthroplasty - a Multicenter, Randomized Controlled Trial in OA Patients (The MultiKnee Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lovisenberg Diakonale Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Haukeland University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Martina Hansen's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Lovisenberg Diakonale Hospital</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 effectiveness of cognitive behavioral therapy&#xD;
      delivered as an e-therapy program, combined with physical exercise delivered by&#xD;
      physiotherapists, for patients on waiting list for total knee arthroplasty. The patients will&#xD;
      be randomized to either 1) a non-surgical program consisting of web-based cognitive&#xD;
      behavioral therapy combined with physiotherapy, 2) total knee arthroplasty (TKA) surgery&#xD;
      followed by web-based cognitive behavioral therapy combined with physiotherapy, or 3) a&#xD;
      control group who undergo TKA followed by standard physiotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is a multidisciplinary trial testing an intervention delivered by physiotherapists.&#xD;
      Up to 20% of total knee arthroplasty (TKA) patients continue to experience moderate/severe&#xD;
      pain 12 months after TKA. While physical therapy (PT) and cognitive-behavior therapy (CBT)&#xD;
      have shown promise for improving outcomes, they have not been evaluated in combination or in&#xD;
      patients at risk for chronic pain after TKA. This trial will evaluate PT+CBT combined, either&#xD;
      as a substitute for or as a supplement to TKA for patients at risk for chronic pain after&#xD;
      TKA.&#xD;
&#xD;
      Pilot/Feasibility study:&#xD;
&#xD;
      The study will include a feasibility/pilot study with 15 patients to be performed from&#xD;
      November 2018. The intervention and study procedures may be modified based on results from&#xD;
      the feasibility/pilot study.&#xD;
&#xD;
      Full scale Randomized Controlled Trial (RCT):&#xD;
&#xD;
      The full-scale RCT will include 282 patients scheduled for TKA. Patients will be randomly&#xD;
      assigned to one of three groups: 1) non-surgical intervention (i.e., PT+CBT), 2) a&#xD;
      combination of TKA with pre- and postoperative PT+CBT, or 3) A control group receiving TKA&#xD;
      and usual care follow-up. Primary outcome: The Pain subscale from the KOOS. The intervention&#xD;
      has the potential to improve outcomes for patients who currently obtain little benefit from&#xD;
      standard TKA.&#xD;
&#xD;
      Cross-sectional observational study: Patients declining to participate in the RCT will be&#xD;
      offered the option to participate in a separate cross-sectional study. The inclusion and&#xD;
      exclusion criteria will be identical to the RCT. Patients who agree to participate in the&#xD;
      cross-sectional study will complete the same baseline questionnaires as in the RCT and are&#xD;
      asked about the reasons they did not want to participate in the RCT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 28, 2019</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the knee injury and osteoarthritis score (KOOS) pain subscale</measure>
    <time_frame>Before randomization, 12 months after treatment start. Also measured at 3, 6, and 24 months after treatment start.12 months after treatment start will be the primary outcome.</time_frame>
    <description>KOOS is a knee-specific, patient administered questionnaire developed to evaluate short- and long-term symptoms and functioning in subjects with knee injury and osteoarthritis. KOOS is validated for use in total knee arthroplasty and has been shown to be a valid, reliable and responsive measure. KOOS is a patient-administered questionnaire.&#xD;
The KOOS is a knee joint specific questionnaire with 42 items designed to assess patients' opinions about their difficulties with activity due to problems with their knees during the past week. The pain subscale of the KOOS consists of 9 items that assess frequency of pain and pain severity in different situations. Each of the 42 items carries equal weighting (0-4), with higher scores indicating better functioning. The pain subscale score will be transformed to a 0-100 scale, with 0 representing extreme knee problems and 100 representing no problems.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Knee injury and osteoarthritis score (KOOS) subscores: Other symptoms, activities of daily living (ADL), function in sport and recreation, and knee-related quality of life (QOL)</measure>
    <time_frame>Before randomization. 3, 6, 12 and 24 months following treatment start</time_frame>
    <description>KOOS is a knee-specific questionnaire developed to evaluate short- and long-term symptoms and functioning in subjects with knee injury and osteoarthritis.&#xD;
The KOOS is a knee joint specific questionnaire with 42 items designed to assess patients' opinions about their difficulties with activity due to problems with their knees during the past week. KOOS has 5 subscales: pain, other symptoms, activities of daily living (ADL), function in sport and recreation, and knee-related QOL. The KOOS has been validated for use in TKA and has been shown to be valid, reliable and responsive. Each of the 42 items carries equal weighting (0-4), with higher scores indicating better functioning. Each of the subscale scores are transformed to a 0-100 scale, with 0 representing extreme knee problems and 100 representing no problems. KOOS is a patient-administered questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The 30 second sit to stand test</measure>
    <time_frame>Before treatment start. 3, 6, 12 and 24 months following treatment start</time_frame>
    <description>The 30-second sit to stand test will be used to assess functional lower extremity strength. This test is performed using a chair of standard height without arms. The participant is encouraged to complete as many full stands as possible within 30 seconds.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brief Pain inventory</measure>
    <time_frame>Before randomization. 3, 6, 12 and 24 months following treatment start</time_frame>
    <description>The Brief Pain Inventory (BPI) will be used to measure pain (56). The BPI is a brief patient-completed questionnaire that consists of four items that measure pain intensity (on an 11-point numeric rating scale from 0-10), seven questions on pain interference with functioning, a body map to localize the pain and one item on pain relief.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EuroQol-5D-5L</measure>
    <time_frame>Before randomization. 3, 6, 12 and 24 months following treatment start</time_frame>
    <description>The widely used EuroQol-5 (EQ-5D-5L) will be used to measure health-related quality of life.&#xD;
The EQ5D-5L consists of two parts: A descriptive system (Mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and the EQ-VAS that record patients self-rated health on a visual analog scale that range from 0 - 100, higher levels indicate better self-rated health.&#xD;
The descriptive system can be converted to a single summary index number where lower levels indicate poorer health-related quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Forgotten Joint Score</measure>
    <time_frame>Before randomization. 3, 6, 12 and 24 months following treatment start</time_frame>
    <description>The Forgotten Joint Score will be used to assess how natural the prosthesis feels after total knee arthroplasty. The scoring system consists of 12 items that assess patients agreement with 12 statements, that range from 1 (never) to 5 (mostly). The raw score is transformed to a 0-100 score and then reversed to obtain the final score. A higher score indicate better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Catastrophizing Scale</measure>
    <time_frame>Before randomization. 3, 6, 12 and 24 months following treatment start</time_frame>
    <description>The Pain Catastrophizing scale (PCS) will be used to measure catastrophic thinking related to pain. The scale consist of 13 items that range from 0 -4. The PCS assesses three dimensions of catastrophizing (i.e., rumination (range 0-16), magnification (range: 0-12, helplessness (range 0 -24). Higher scores indicate higher levels of catastrophic thinking related to pain. A total score can be computed by summing responses to all 13 items. PCS total scores range from 0-52. Higher scores indicate higher levels of catastrophic thinking related to pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient-acceptable symptom state, perceived treatment failure.</measure>
    <time_frame>At 3, 6, 12 and 24 months following treatment start.</time_frame>
    <description>Patient-acceptable symptom state will be measured by a single item question. The patient state wether they consider their knee function satisfactory or not (Yes/No).&#xD;
Perceived treatment failure will be measured by a single item question. The patient state whether their situation is so dissatisfying that they consider the treatment as a failure (Yes/No).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global perceived effect</measure>
    <time_frame>At 3, 6, 12 and 24 months following treatment start.</time_frame>
    <description>The patient rate their level of knee problems compared to their condition before they started their treatment, by choosing on of seven statements that describe the level of improvement/worsening.&#xD;
The statements range from &quot;better - an important improvement&quot; - to &quot;worse, an important worsening&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events/serious adverse events</measure>
    <time_frame>From treatment start until 24 months following treatment start.</time_frame>
    <description>All events reported by participant, physiotherapist or documented in the patient's hospital record.&#xD;
During surgery: Number of patients with fractures (Tibia, patella, femur), nerve or vascular injury, rupture of patella tendon, other.&#xD;
Postoperatively: Number of patients with deep infection, any secondary surgery (e.g., skin necrosis or scar tissue adherences, DAIR, MUA, secondary insertion of patella component, partial/total revision surgery), supracondylar femur fracture, patella fracture, permanent n. peroneus paresis, aseptic loosening, polyethylene defect (tibia or patella), instability requiring intervention, thrombophlebitis demanding anticoagulant treatment, pulmonary embolism, myocardial infarction, cerebral insult, other events.&#xD;
Patient-reported myocardial infarction, cerebral insult, pulmonary embolism or DVT within 3 months following intervention.&#xD;
All events reported by patients or physiotherapists - open probe questionnairing</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pittsburgh Sleep Quality Index</measure>
    <time_frame>Before randomization. 3, 6, 12 and 24 months following treatment start</time_frame>
    <description>The Pittsburgh Sleep Quality index (PSQI) is a widely-used self-report measure of sleep disturbance during the past month. The PSQI consists of 19 items that measures different aspects of sleep. The 19 items produce 7 component scores (i.e., duration of sleep, sleep disturbance, sleep latency, day dysfunction due to sleepiness, sleep efficiency, overall sleep quality, need for sleep medications) each ranging from 0-3 where higher score indicate poorer sleep. All component scores can be summarized to a global score that range from 0 to 21 where higher scores indicate poorer sleep quality. The PSQI has good validity and reliability.</description>
  </other_outcome>
  <other_outcome>
    <measure>The Hospital Anxiety and Depression Scale</measure>
    <time_frame>Before randomization. 3, 6, 12 and 24 months following treatment start</time_frame>
    <description>The Hospital Anxiety and Depression Scale (HADS) will be used to measure self-reported psychological distress (depression and anxiety). The scale consists of 14 items, 7 on the depression subscale and 7 on the anxiety subscale. The Norwegian version has excellent psychometric properties. Each subscale range from 0-21 where higher scores indicate higher levels of anxiety or depression. A total score (range 0 - 42) can be calculated from summarizing all the 14 items. Higher scores indicate higher levels of anxiety/depression.</description>
  </other_outcome>
  <other_outcome>
    <measure>The Fear-Avoidance Belief Questionnaire</measure>
    <time_frame>Before randomization. 3, 6, 12 and 24 months following treatment start</time_frame>
    <description>The Fear-Avoidance Belief Questionnaire (FABQ) will be used to measure pain-related fear of movement. The instrument consists of 2 subscales, fear-avoidance beliefs for work, and fear-avoidance beliefs for physical activity (FABQ-PA). Only the FABQ-PA subscale will be used in this study. The FABQ-PA consists of 4 items where patients rate their agreement with 5 statements about pain and physical activity. The FABQ-PA range from 0-24 and higher scores indicate higher levels of pain-related fear of movement.</description>
  </other_outcome>
  <other_outcome>
    <measure>Health Locus of Control Scale</measure>
    <time_frame>Before randomization. 3, 12 and 24 months following treatment start</time_frame>
    <description>The Health Locus of Control Scale (HLCS) will be used to measure patients' anticipations between own health and disease behavior and consequences of the behavior. The scale consists of 18 statements. Patients rate their agreement on a 6 point likert scale ranging from disagrees completely to agrees completely. Scoring: The scoring system consists of 3 subscales: The Internal Locus of Control, the Powerful Others Health Locus of Control, and the Chance Health Locus of control. The scores are obtained by summing items for each subscale. Higher scores indicate stronger agreement or inclination towards that particular subscale.</description>
  </other_outcome>
  <other_outcome>
    <measure>Self-reported level of physical activity</measure>
    <time_frame>Before randomization. 3, 6, 12 and 24 months following treatment start</time_frame>
    <description>Self-reported level of physical activity will be measured using two items from the Norwegian Hunt2 survey that assess frequency of light and hard physical activity, and the Stages of Change for physical activity. The Stages of Change for physical activity assess patients' readiness for physical activity. Patients rate their agreement with five different statements about physical activity.</description>
  </other_outcome>
  <other_outcome>
    <measure>The ActiGraph Professional single-axis accelerometer</measure>
    <time_frame>Before treatment start. 6, 12 and 24 months following treatment start</time_frame>
    <description>The ActiGraph Professional single-axis accelerometer, a body worn sensor system to measure physical activity, will be used to measure time in sedentary and active positions, duration of activity and number of steps during walking</description>
  </other_outcome>
  <other_outcome>
    <measure>The 40 meters walk test</measure>
    <time_frame>Before treatment start. 3, 6, 12 and 24 months following treatment start</time_frame>
    <description>The 40 meter walk test: The patient is instructed to walk 40 meter under timing.</description>
  </other_outcome>
  <other_outcome>
    <measure>Stair Climb Test</measure>
    <time_frame>Before treatment start. 3, 6, 12 and 24 months following treatment start</time_frame>
    <description>The Stair Climb Test will be used to measure ascending and descending stair activity, and lower body strength and balance, measured as a participants' time in seconds to ascend and descend a flight of stairs.</description>
  </other_outcome>
  <other_outcome>
    <measure>Registry-based data on use of health care resources</measure>
    <time_frame>From before randomization until 3, 6, 12 and 24 months after treatment start.</time_frame>
    <description>Use of health care resources will be measured using registry data from the KUHR-system (i.e., control and payment of reimbursements to health service providers), the Norwegian Patient Registry (NPR) FD Trygd social security database, the Norwegian Prescription Database and the Norwegian Arthroplasty registry. All information will be anonymized and linked to each patient using a code number before analysis.</description>
  </other_outcome>
  <other_outcome>
    <measure>Radiographs: weightbearing AP, lateral view, Rosenberg view and long leg weightbearing AP view (HKA)</measure>
    <time_frame>Before treatment start, 12 months following treatment start.</time_frame>
    <description>X-rays including weightbearing AP, lateral view, Rosenberg view and long leg weightbearing AP view (HKA) weightbearing AP view (HKA). OA severity grading will be performed according to the Kellgren-Lawrence grading system and cartilage thickness.</description>
  </other_outcome>
  <other_outcome>
    <measure>Screening and recruitment of patients (pilot study with 15 patients).</measure>
    <time_frame>Baseline T1 before randomization</time_frame>
    <description>Number of patients undergoing screening, considered for inclusion, eligible for inclusion, consenting to participate and undergoing randomization</description>
  </other_outcome>
  <other_outcome>
    <measure>Adherence to the intervention (pilot study with 15 patients)</measure>
    <time_frame>From treatment start until 12 weeks following treatment start.</time_frame>
    <description>Number of patients receiving the full dose of the intervention. adverse events, recruitment, screening and randomization, retention in study/loss to follow-up.</description>
  </other_outcome>
  <other_outcome>
    <measure>Acceptability of the intervention (pilot study with 15 patients)</measure>
    <time_frame>From treatment start until 12 weeks following treatment start.</time_frame>
    <description>Number of patients feeling overwhelmed or burdened by the intervention. Number of patients not completing the intervention due to feeling overwhelmed ro burdened by the intervention.</description>
  </other_outcome>
  <other_outcome>
    <measure>Level of electronic health literacy</measure>
    <time_frame>Before treatment start, 6 months after treatment start</time_frame>
    <description>The Electronic Health Literacy Questionnaire (e-HLQ) (44) will be used to measure patients level of electronic health literacy prior to, and six months following surgery. In this study, 4 domains will be assessed: 1) using technology to process health information, 2) understanding of health concepts and language, 3) ability to actively engage with digital services, 4) motivated to engage with digital services. The scores range 1-4, with high scores indicating high e-health literacy.</description>
  </other_outcome>
  <other_outcome>
    <measure>Level of health literacy</measure>
    <time_frame>Before treatment start, 6 months after treatment start</time_frame>
    <description>The International Health Literacy Population survey Questionnaire 2019-2021(HLS19-Q47) will be used to measure patients' level of health literacy prior to, and six months following surgery. The original HLS-19-Q47 consist of 47 items. In this study, 2 domains will be assessed: 1) Health promotion and 2) General health literacy.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">282</enrollment>
  <condition>Osteoarthritis; Primary</condition>
  <condition>Degenerative Joint Disease of Knee</condition>
  <arm_group>
    <arm_group_label>Non-surgical group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Osteoarthritis education, exercise and eCBT</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combined group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Total knee arthroplasty + osteoarthritis education, exercise and eCBT</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Surgery only (standard care)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Total knee arthroplasty + standard physiotherapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Osteoarthritis education, exercise and CBT</intervention_name>
    <description>Osteoarthritis Education&#xD;
60-min session by AktivA trained PT)&#xD;
Signs/symptoms, risk factors, weight control, treatment&#xD;
Importance of physical activity&#xD;
Appropriate activity &amp; training modalities&#xD;
Exercise and CBT Support&#xD;
60-min sessions/week for 12 weeks (a total of 24 sessions) led by AktivA and CBT trained PT)&#xD;
Warm-up session&#xD;
Strengthening exercises&#xD;
Functional exercises&#xD;
Stretching&#xD;
Monitoring of CBT progress&#xD;
Review of CBT lessons learned&#xD;
Integration of CBT skills&#xD;
Enhance motivation to continue&#xD;
Online CBT (iCBT) (10 modules completed at home)&#xD;
Pain causes &amp; prevention&#xD;
Pain management&#xD;
Health promotion &amp; stress reduction at home &amp; work&#xD;
Adapting for leisure &amp; work&#xD;
Controlling flare-ups&#xD;
Maintaining &amp; improving results</description>
    <arm_group_label>Combined group</arm_group_label>
    <arm_group_label>Non-surgical group</arm_group_label>
    <other_name>AktivA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Total Knee Arthroplasty</intervention_name>
    <description>Standard total knee arthroplasty will be performed.</description>
    <arm_group_label>Combined group</arm_group_label>
    <arm_group_label>Surgery only (standard care)</arm_group_label>
    <other_name>knee replacement</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Scheduled for TKA for OA at Lovisenberg, Oslo; Martina Hansen, Bærum, or Coastal&#xD;
             Hospital Hagevik, Bergen&#xD;
&#xD;
          2. Age 18 - 79 years&#xD;
&#xD;
          3. ASA grade 1-3&#xD;
&#xD;
          4. KL grade 3 or 4&#xD;
&#xD;
          5. BMI&lt;40&#xD;
&#xD;
          6. Able to read and write in Norwegian&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of dementia or sero-positive rheumatic disease&#xD;
&#xD;
          -  Previously undergone uni or patellofemoral prosthesis in the index knee&#xD;
&#xD;
          -  Large axis deviation or instability requiring use of hinged implants&#xD;
&#xD;
          -  Scheduled for unicompartmental arthroplasty or revision surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anners Lerdal, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lovisenberg Diaconal Hospital, University of Oslo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Arild Aamodt, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lovisenberg Diakonale Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Maren F Lindberg, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Lovisenberg Diakonale Hospital/University of Oslo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kari Indrekvam, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Haukeland University Hospital - Kysthospitalet Hagevik/University of Bergen</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stig Heir, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Martina Hansens Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Maren Falch Lindberg, PhD</last_name>
    <phone>+4794815762</phone>
    <email>mfli@lds.no</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Anners Lerdal, PhD</last_name>
    <phone>+4795033144</phone>
    <email>anners.lerdal@medisin.uio.no</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Haukeland University Hospital - Kysthospitalet Hagevik</name>
      <address>
        <city>Bergen</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kari Indrekvam, PhD</last_name>
      <phone>+47913 32 899</phone>
      <email>kari.indrekvam@helse-bergen.no</email>
    </contact>
    <contact_backup>
      <last_name>Mona Badawy, PhD</last_name>
      <phone>+4756565927</phone>
      <email>mona.badawy@helse-bergen.no</email>
    </contact_backup>
    <investigator>
      <last_name>Turid Rognsvåg, Msc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mona Badawy, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Lovisenberg Diaconal Hospital</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maren F Lindberg, PhD</last_name>
      <phone>+4794815762</phone>
      <email>m.k.f.lindberg@medisin.uio.no</email>
    </contact>
    <contact_backup>
      <last_name>Anners Lerdal, PhD</last_name>
      <phone>22358206</phone>
      <email>anners.lerdal@medisin.uio.no</email>
    </contact_backup>
    <investigator>
      <last_name>Anners Lerdal, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Arild Aamodt, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Martina Hansens Hospital</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stig Heir, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Nina J Kise, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>November 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>January 16, 2023</last_update_submitted>
  <last_update_submitted_qc>January 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Total knee arthroplasty</keyword>
  <keyword>Physiotherapy</keyword>
  <keyword>Cognitive behavioral therapy</keyword>
  <keyword>e-therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Joint Diseases</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03771430
org study id: MultiKnee Trial
nct id: NCT03771430
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to investigate the effectiveness of cognitive behavioral therapy
      delivered as an e-therapy program, combined with physical exercise delivered by
      physiotherapists, for patients on waiting list for total knee arthroplasty. The patients will
      be randomized to either 1) a non-surgical program consisting of web-based cognitive
      behavioral therapy combined with physiotherapy, 2) total knee arthroplasty (TKA) surgery
      followed by web-based cognitive behavioral therapy combined with physiotherapy, or 3) a
      control group who undergo TKA followed by standard physiotherapy.
The study is a multidisciplinary trial testing an intervention delivered by physiotherapists.
      Up to 20% of total knee arthroplasty (TKA) patients continue to experience moderate/severe
      pain 12 months after TKA. While physical therapy (PT) and cognitive-behavior therapy (CBT)
      have shown promise for improving outcomes, they have not been evaluated in combination or in
      patients at risk for chronic pain after TKA. This trial will evaluate PT+CBT combined, either
      as a substitute for or as a supplement to TKA for patients at risk for chronic pain after
      TKA.

      Pilot/Feasibility study:

      The study will include a feasibility/pilot study with 15 patients to be performed from
      November 2018. The intervention and study procedures may be modified based on results from
      the feasibility/pilot study.

      Full scale Randomized Controlled Trial (RCT):

      The full-scale RCT will include 282 patients scheduled for TKA. Patients will be randomly
      assigned to one of three groups: 1) non-surgical intervention (i.e., PT+CBT), 2) a
      combination of TKA with pre- and postoperative PT+CBT, or 3) A control group receiving TKA
      and usual care follow-up. Primary outcome: The Pain subscale from the KOOS. The intervention
      has the potential to improve outcomes for patients who currently obtain little benefit from
      standard TKA.

      Cross-sectional observational study: Patients declining to participate in the RCT will be
      offered the option to participate in a separate cross-sectional study. The inclusion and
      exclusion criteria will be identical to the RCT. Patients who agree to participate in the
      cross-sectional study will complete the same baseline questionnaires as in the RCT and are
      asked about the reasons they did not want to participate in the RCT.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in the knee injury and osteoarthritis score (KOOS) pain subscale
time frame: Before randomization, 12 months after treatment start. Also measured at 3, 6, and 24 months after treatment start.12 months after treatment start will be the primary outcome.
description: KOOS is a knee-specific, patient administered questionnaire developed to evaluate short- and long-term symptoms and functioning in subjects with knee injury and osteoarthritis. KOOS is validated for use in total knee arthroplasty and has been shown to be a valid, reliable and responsive measure. KOOS is a patient-administered questionnaire.
The KOOS is a knee joint specific questionnaire with 42 items designed to assess patients' opinions about their difficulties with activity due to problems with their knees during the past week. The pain subscale of the KOOS consists of 9 items that assess frequency of pain and pain severity in different situations. Each of the 42 items carries equal weighting (0-4), with higher scores indicating better functioning. The pain subscale score will be transformed to a 0-100 scale, with 0 representing extreme knee problems and 100 representing no problems.
measure: Knee injury and osteoarthritis score (KOOS) subscores: Other symptoms, activities of daily living (ADL), function in sport and recreation, and knee-related quality of life (QOL)
time frame: Before randomization. 3, 6, 12 and 24 months following treatment start
description: KOOS is a knee-specific questionnaire developed to evaluate short- and long-term symptoms and functioning in subjects with knee injury and osteoarthritis.
The KOOS is a knee joint specific questionnaire with 42 items designed to assess patients' opinions about their difficulties with activity due to problems with their knees during the past week. KOOS has 5 subscales: pain, other symptoms, activities of daily living (ADL), function in sport and recreation, and knee-related QOL. The KOOS has been validated for use in TKA and has been shown to be valid, reliable and responsive. Each of the 42 items carries equal weighting (0-4), with higher scores indicating better functioning. Each of the subscale scores are transformed to a 0-100 scale, with 0 representing extreme knee problems and 100 representing no problems. KOOS is a patient-administered questionnaire.
measure: The 30 second sit to stand test
time frame: Before treatment start. 3, 6, 12 and 24 months following treatment start
description: The 30-second sit to stand test will be used to assess functional lower extremity strength. This test is performed using a chair of standard height without arms. The participant is encouraged to complete as many full stands as possible within 30 seconds.
measure: Brief Pain inventory
time frame: Before randomization. 3, 6, 12 and 24 months following treatment start
description: The Brief Pain Inventory (BPI) will be used to measure pain (56). The BPI is a brief patient-completed questionnaire that consists of four items that measure pain intensity (on an 11-point numeric rating scale from 0-10), seven questions on pain interference with functioning, a body map to localize the pain and one item on pain relief.
measure: EuroQol-5D-5L
time frame: Before randomization. 3, 6, 12 and 24 months following treatment start
description: The widely used EuroQol-5 (EQ-5D-5L) will be used to measure health-related quality of life.
The EQ5D-5L consists of two parts: A descriptive system (Mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and the EQ-VAS that record patients self-rated health on a visual analog scale that range from 0 - 100, higher levels indicate better self-rated health.
The descriptive system can be converted to a single summary index number where lower levels indicate poorer health-related quality of life.
measure: The Forgotten Joint Score
time frame: Before randomization. 3, 6, 12 and 24 months following treatment start
description: The Forgotten Joint Score will be used to assess how natural the prosthesis feels after total knee arthroplasty. The scoring system consists of 12 items that assess patients agreement with 12 statements, that range from 1 (never) to 5 (mostly). The raw score is transformed to a 0-100 score and then reversed to obtain the final score. A higher score indicate better outcome.
measure: Pain Catastrophizing Scale
time frame: Before randomization. 3, 6, 12 and 24 months following treatment start
description: The Pain Catastrophizing scale (PCS) will be used to measure catastrophic thinking related to pain. The scale consist of 13 items that range from 0 -4. The PCS assesses three dimensions of catastrophizing (i.e., rumination (range 0-16), magnification (range: 0-12, helplessness (range 0 -24). Higher scores indicate higher levels of catastrophic thinking related to pain. A total score can be computed by summing responses to all 13 items. PCS total scores range from 0-52. Higher scores indicate higher levels of catastrophic thinking related to pain.
measure: Patient-acceptable symptom state, perceived treatment failure.
time frame: At 3, 6, 12 and 24 months following treatment start.
description: Patient-acceptable symptom state will be measured by a single item question. The patient state wether they consider their knee function satisfactory or not (Yes/No).
Perceived treatment failure will be measured by a single item question. The patient state whether their situation is so dissatisfying that they consider the treatment as a failure (Yes/No).
measure: Global perceived effect
time frame: At 3, 6, 12 and 24 months following treatment start.
description: The patient rate their level of knee problems compared to their condition before they started their treatment, by choosing on of seven statements that describe the level of improvement/worsening.
The statements range from "better - an important improvement" - to "worse, an important worsening".
measure: Adverse events/serious adverse events
time frame: From treatment start until 24 months following treatment start.
description: All events reported by participant, physiotherapist or documented in the patient's hospital record.
During surgery: Number of patients with fractures (Tibia, patella, femur), nerve or vascular injury, rupture of patella tendon, other.
Postoperatively: Number of patients with deep infection, any secondary surgery (e.g., skin necrosis or scar tissue adherences, DAIR, MUA, secondary insertion of patella component, partial/total revision surgery), supracondylar femur fracture, patella fracture, permanent n. peroneus paresis, aseptic loosening, polyethylene defect (tibia or patella), instability requiring intervention, thrombophlebitis demanding anticoagulant treatment, pulmonary embolism, myocardial infarction, cerebral insult, other events.
Patient-reported myocardial infarction, cerebral insult, pulmonary embolism or DVT within 3 months following intervention.
All events reported by patients or physiotherapists - open probe questionnairing
measure: Pittsburgh Sleep Quality Index
time frame: Before randomization. 3, 6, 12 and 24 months following treatment start
description: The Pittsburgh Sleep Quality index (PSQI) is a widely-used self-report measure of sleep disturbance during the past month. The PSQI consists of 19 items that measures different aspects of sleep. The 19 items produce 7 component scores (i.e., duration of sleep, sleep disturbance, sleep latency, day dysfunction due to sleepiness, sleep efficiency, overall sleep quality, need for sleep medications) each ranging from 0-3 where higher score indicate poorer sleep. All component scores can be summarized to a global score that range from 0 to 21 where higher scores indicate poorer sleep quality. The PSQI has good validity and reliability.
measure: The Hospital Anxiety and Depression Scale
time frame: Before randomization. 3, 6, 12 and 24 months following treatment start
description: The Hospital Anxiety and Depression Scale (HADS) will be used to measure self-reported psychological distress (depression and anxiety). The scale consists of 14 items, 7 on the depression subscale and 7 on the anxiety subscale. The Norwegian version has excellent psychometric properties. Each subscale range from 0-21 where higher scores indicate higher levels of anxiety or depression. A total score (range 0 - 42) can be calculated from summarizing all the 14 items. Higher scores indicate higher levels of anxiety/depression.
measure: The Fear-Avoidance Belief Questionnaire
time frame: Before randomization. 3, 6, 12 and 24 months following treatment start
description: The Fear-Avoidance Belief Questionnaire (FABQ) will be used to measure pain-related fear of movement. The instrument consists of 2 subscales, fear-avoidance beliefs for work, and fear-avoidance beliefs for physical activity (FABQ-PA). Only the FABQ-PA subscale will be used in this study. The FABQ-PA consists of 4 items where patients rate their agreement with 5 statements about pain and physical activity. The FABQ-PA range from 0-24 and higher scores indicate higher levels of pain-related fear of movement.
measure: Health Locus of Control Scale
time frame: Before randomization. 3, 12 and 24 months following treatment start
description: The Health Locus of Control Scale (HLCS) will be used to measure patients' anticipations between own health and disease behavior and consequences of the behavior. The scale consists of 18 statements. Patients rate their agreement on a 6 point likert scale ranging from disagrees completely to agrees completely. Scoring: The scoring system consists of 3 subscales: The Internal Locus of Control, the Powerful Others Health Locus of Control, and the Chance Health Locus of control. The scores are obtained by summing items for each subscale. Higher scores indicate stronger agreement or inclination towards that particular subscale.
measure: Self-reported level of physical activity
time frame: Before randomization. 3, 6, 12 and 24 months following treatment start
description: Self-reported level of physical activity will be measured using two items from the Norwegian Hunt2 survey that assess frequency of light and hard physical activity, and the Stages of Change for physical activity. The Stages of Change for physical activity assess patients' readiness for physical activity. Patients rate their agreement with five different statements about physical activity.
measure: The ActiGraph Professional single-axis accelerometer
time frame: Before treatment start. 6, 12 and 24 months following treatment start
description: The ActiGraph Professional single-axis accelerometer, a body worn sensor system to measure physical activity, will be used to measure time in sedentary and active positions, duration of activity and number of steps during walking
measure: The 40 meters walk test
time frame: Before treatment start. 3, 6, 12 and 24 months following treatment start
description: The 40 meter walk test: The patient is instructed to walk 40 meter under timing.
measure: Stair Climb Test
time frame: Before treatment start. 3, 6, 12 and 24 months following treatment start
description: The Stair Climb Test will be used to measure ascending and descending stair activity, and lower body strength and balance, measured as a participants' time in seconds to ascend and descend a flight of stairs.
measure: Registry-based data on use of health care resources
time frame: From before randomization until 3, 6, 12 and 24 months after treatment start.
description: Use of health care resources will be measured using registry data from the KUHR-system (i.e., control and payment of reimbursements to health service providers), the Norwegian Patient Registry (NPR) FD Trygd social security database, the Norwegian Prescription Database and the Norwegian Arthroplasty registry. All information will be anonymized and linked to each patient using a code number before analysis.
measure: Radiographs: weightbearing AP, lateral view, Rosenberg view and long leg weightbearing AP view (HKA)
time frame: Before treatment start, 12 months following treatment start.
description: X-rays including weightbearing AP, lateral view, Rosenberg view and long leg weightbearing AP view (HKA) weightbearing AP view (HKA). OA severity grading will be performed according to the Kellgren-Lawrence grading system and cartilage thickness.
measure: Screening and recruitment of patients (pilot study with 15 patients).
time frame: Baseline T1 before randomization
description: Number of patients undergoing screening, considered for inclusion, eligible for inclusion, consenting to participate and undergoing randomization
measure: Adherence to the intervention (pilot study with 15 patients)
time frame: From treatment start until 12 weeks following treatment start.
description: Number of patients receiving the full dose of the intervention. adverse events, recruitment, screening and randomization, retention in study/loss to follow-up.
measure: Acceptability of the intervention (pilot study with 15 patients)
time frame: From treatment start until 12 weeks following treatment start.
description: Number of patients feeling overwhelmed or burdened by the intervention. Number of patients not completing the intervention due to feeling overwhelmed ro burdened by the intervention.
measure: Level of electronic health literacy
time frame: Before treatment start, 6 months after treatment start
description: The Electronic Health Literacy Questionnaire (e-HLQ) (44) will be used to measure patients level of electronic health literacy prior to, and six months following surgery. In this study, 4 domains will be assessed: 1) using technology to process health information, 2) understanding of health concepts and language, 3) ability to actively engage with digital services, 4) motivated to engage with digital services. The scores range 1-4, with high scores indicating high e-health literacy.
measure: Level of health literacy
time frame: Before treatment start, 6 months after treatment start
description: The International Health Literacy Population survey Questionnaire 2019-2021(HLS19-Q47) will be used to measure patients' level of health literacy prior to, and six months following surgery. The original HLS-19-Q47 consist of 47 items. In this study, 2 domains will be assessed: 1) Health promotion and 2) General health literacy.
arm group label: Non-surgical group
arm group type: Experimental
description: Osteoarthritis education, exercise and eCBT
arm group label: Combined group
arm group type: Experimental
description: Total knee arthroplasty + osteoarthritis education, exercise and eCBT
arm group label: Surgery only (standard care)
arm group type: Active Comparator
description: Total knee arthroplasty + standard physiotherapy
intervention type: Behavioral
intervention name: Osteoarthritis education, exercise and CBT
description: Osteoarthritis Education
60-min session by AktivA trained PT)
Signs/symptoms, risk factors, weight control, treatment
Importance of physical activity
Appropriate activity & training modalities
Exercise and CBT Support
60-min sessions/week for 12 weeks (a total of 24 sessions) led by AktivA and CBT trained PT)
Warm-up session
Strengthening exercises
Functional exercises
Stretching
Monitoring of CBT progress
Review of CBT lessons learned
Integration of CBT skills
Enhance motivation to continue
Online CBT (iCBT) (10 modules completed at home)
Pain causes & prevention
Pain management
Health promotion & stress reduction at home & work
Adapting for leisure & work
Controlling flare-ups
Maintaining & improving results
arm group label: Combined group
arm group label: Non-surgical group
other name: AktivA
intervention type: Procedure
intervention name: Total Knee Arthroplasty
description: Standard total knee arthroplasty will be performed.
arm group label: Combined group
arm group label: Surgery only (standard care)
other name: knee replacement
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: No
last name: Anners Lerdal, PhD
role: Principal Investigator
affiliation: Lovisenberg Diaconal Hospital, University of Oslo
last name: Arild Aamodt, PhD
role: Principal Investigator
affiliation: Lovisenberg Diakonale Hospital
last name: Maren F Lindberg, PhD
role: Study Director
affiliation: Lovisenberg Diakonale Hospital/University of Oslo
last name: Kari Indrekvam, PhD
role: Study Chair
affiliation: Haukeland University Hospital - Kysthospitalet Hagevik/University of Bergen
last name: Stig Heir, PhD
role: Study Chair
affiliation: Martina Hansens Hospital
last name: Maren Falch Lindberg, PhD
phone: +4794815762
email: mfli@lds.no
last name: Anners Lerdal, PhD
phone: +4795033144
email: anners.lerdal@medisin.uio.no
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Norway
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Joint Diseases
mesh term: Osteoarthritis, Knee
sharing ipd: No