<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/NCT01682980</url>
  </required_header>
  <id_info>
    <org_study_id>2012/334</org_study_id>
    <nct_id>NCT01682980</nct_id>
  </id_info>
  <brief_title>Efficacy of Exercise on Quality of Life and Physical Function in Patients With Knee Osteoarthritis</brief_title>
  <official_title>Efficacy of Strength and Aerobic Exercise on Patient-reported Outcomes in Patients With Knee Osteoarthritis - A Randomised Controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oslo University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital, Akershus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oslo Metropolitan University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Oslo University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall contribution of this study is to increase the knowledge of the efficacy of&#xD;
      strength and aerobic exercise on knee related quality of life, knee pain, and physical&#xD;
      function in patients with knee osteoarthritis (OA). Knee OA is one of the most important&#xD;
      diseases within musculoskeletal conditions affecting a considerable number of people&#xD;
      worldwide. This randomized controlled trial will involve one intervention group delivered&#xD;
      strength exercises and one group delivered aerobic exercise (ergometer cycling). The two&#xD;
      intervention groups will be compared to a control group undergoing usual care.&#xD;
      Cost-effectiveness analysis will be performed comparing the three groups. The study is funded&#xD;
      from The Research Council of Norway.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial aimed to recruit 207 study participants randomly allocated to three arms. The&#xD;
      participants had to have symptomatic knee osteoarthritis verified by grade 2-3 using the&#xD;
      Kellgren and Lawrence radiographic classification system, and they had to have knee pain most&#xD;
      of the days the last month and fulfil 2/3 of the ACR clinical criteria. Participants with&#xD;
      other serious comorbidities or self-reported BMI &gt;35 were included.&#xD;
&#xD;
      The interventions consisted of structured strength training program over 12-14 weeks, and a&#xD;
      structured stationary cycling program for 12-14 weeks.&#xD;
&#xD;
      Primary outcome was the KOOS knee-related quality of life subscale at the 1 year follow-up.&#xD;
      Secondary outcomes were other patient reported outcomes, muscle strength, and peak oxygen&#xD;
      consumption at the 4-month and 1 year follow-up, and over time (1-year).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Anticipated">December 2025</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>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Knee-related quality of life</measure>
    <time_frame>1 year</time_frame>
    <description>Primary outcome for the study will be the quality of life subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS) (0-100 scale). 0 is very poor knee-related quality of life, while 100 indicates normal knee-related quality of life.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Knee function</measure>
    <time_frame>4 months and 1 year</time_frame>
    <description>The KOOS is a self-administered knee-specific questionnaire containing 5-item Likert scales on pain, other symptoms, activities of daily living (ADL), function in sports and recreation and knee-related quality of life (QOL). Each scale goes from 0-100, 0 indicating worse function and 100 representing normal function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life</measure>
    <time_frame>4 months and 1 year</time_frame>
    <description>Euro Quality of life 5 dimensions 5 level (EQ-5D-5L) will be used to measure health related quality of life. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EuroQol (EQ) Visual analogue scale (VAS) records the patient's self-rated health on a vertical visual analogue scale. This can be used as a quantitative measure of health outcome that reflects the patient's own judgement. The scores on these five dimensions can be presented as a health profile or can be converted to a single summary index number (utility) reflecting preferability compared to other health profiles.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic osteoarthritis progression</measure>
    <time_frame>2 years</time_frame>
    <description>Conventional x-rays will be used to assess radiographic progression of osteoarthritis</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Isokinetic muscle strength</measure>
    <time_frame>4 months and 1 year</time_frame>
    <description>Isokinetic muscle strength will be measured in a Biodex6000 machine. The participants sit in a standardised position and flex/extend their knees at 60 degrees/second. The peak torque value of the five repetitions is recorded.</description>
  </other_outcome>
  <other_outcome>
    <measure>Maximal oxygen consumption (VO2max)</measure>
    <time_frame>4 months and 1 year</time_frame>
    <description>VO2max is measured using an incremental ramp test procedure on a stationary bike, designed to achieve supramaximal workloads within ~4-6 min. The workload was increased by 25 watts every 30 second to total exhaustion.</description>
  </other_outcome>
  <other_outcome>
    <measure>Self-efficacy for pain</measure>
    <time_frame>4 months and 1 year</time_frame>
    <description>Arthritis self-efficacy scale (ASES) was included to measure self-efficacy for pain. A modified version of ASES containing 11 questions regarding the patient's certainty to perform various tasks related to pain and symptoms, where each item is rated from 1 (very uncertain) to 5 (very certain) was used.</description>
  </other_outcome>
  <other_outcome>
    <measure>Total knee replacement</measure>
    <time_frame>5 years</time_frame>
    <description>We will register continuously numbers of total knee replacements during the follow-up years.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">207</enrollment>
  <condition>Osteoarthritis</condition>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Strength training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The strength group include progressive strength training and neuromuscular exercises. The inclusion will be performed 2-3 times a week for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aerobic exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The aerobic exercise group will cycle on an ergometer bicycle 2-3 times a week for 12 weeks on moderate loading. The loading will be controlled by a heart rate monitor and is defined as 75% of maximal heart rate (calculated with formula for maximal heart rate reserve).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The control group will do as usual.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Strength training</intervention_name>
    <description>The strength training will be delivered 2-3 times per week for 12 weeks, 5-8 repetitions maximum in 3 series. The patients must warm up 5 minutes on an ergometer cycle. The following muscle groups will be trained: Quadriceps and hamstrings, hip muscles (abductors and extensors), calf muscles. A home exercise program will be delivered including one leg exercises and balance exercises. Progression will follow a 2+ principle. For instance, when the study participant is able to perform 2 more repetitions, more loads are required.</description>
    <arm_group_label>Strength training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Aerobic exercise</intervention_name>
    <description>The aerobic exercise program include ergometer cycling for at least 45 minutes 2-3 times a week on 75-80% of max heart rate will be required.</description>
    <arm_group_label>Aerobic exercise</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women and men aged 35-70 years&#xD;
&#xD;
          -  Clinical knee OA according to the American College of Rheumatology Clinical Criteria&#xD;
&#xD;
          -  Kellgren and Lawrence radiographic OA grade 2 and 3 (mild to moderate radiographic OA)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe knee OA according to the Kellgren and Lawrence classification (grade 4)&#xD;
&#xD;
          -  Other known major musculoskeletal impairments in the lower extremities or the back or&#xD;
             prostheses in any joint of the lower extremities&#xD;
&#xD;
          -  Known coronary heart diseases or cancer&#xD;
&#xD;
          -  Body mass index &gt; 35&#xD;
&#xD;
          -  Scheduled for surgery in any joint&#xD;
&#xD;
          -  Known mental or psychologic diseases&#xD;
&#xD;
          -  Known drug abuse&#xD;
&#xD;
          -  Persons who already perform sports related moderate physical activity more than two&#xD;
             times a week&#xD;
&#xD;
          -  Contraindications for magnetic resonance imaging (specific point list at Oslo&#xD;
             University Hospital, radiographic department)&#xD;
&#xD;
          -  Not speaking Norwegian language&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>May Arna Risberg, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Oslo University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oslo University Hospital</name>
      <address>
        <city>Oslo</city>
        <zip>0407</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>September 7, 2012</study_first_submitted>
  <study_first_submitted_qc>September 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <last_update_submitted>April 13, 2023</last_update_submitted>
  <last_update_submitted_qc>April 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oslo University Hospital</investigator_affiliation>
    <investigator_full_name>Britt Elin Øiestad</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Osteoarthritis</keyword>
  <keyword>Pain</keyword>
  <keyword>Exercise</keyword>
  <keyword>Function</keyword>
  <keyword>Cartilage quality</keyword>
  <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>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 30, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/80/NCT01682980/SAP_001.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/NCT01682980
org study id: 2012/334
nct id: NCT01682980
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The overall contribution of this study is to increase the knowledge of the efficacy of
      strength and aerobic exercise on knee related quality of life, knee pain, and physical
      function in patients with knee osteoarthritis (OA). Knee OA is one of the most important
      diseases within musculoskeletal conditions affecting a considerable number of people
      worldwide. This randomized controlled trial will involve one intervention group delivered
      strength exercises and one group delivered aerobic exercise (ergometer cycling). The two
      intervention groups will be compared to a control group undergoing usual care.
      Cost-effectiveness analysis will be performed comparing the three groups. The study is funded
      from The Research Council of Norway.
The trial aimed to recruit 207 study participants randomly allocated to three arms. The
      participants had to have symptomatic knee osteoarthritis verified by grade 2-3 using the
      Kellgren and Lawrence radiographic classification system, and they had to have knee pain most
      of the days the last month and fulfil 2/3 of the ACR clinical criteria. Participants with
      other serious comorbidities or self-reported BMI >35 were included.

      The interventions consisted of structured strength training program over 12-14 weeks, and a
      structured stationary cycling program for 12-14 weeks.

      Primary outcome was the KOOS knee-related quality of life subscale at the 1 year follow-up.
      Secondary outcomes were other patient reported outcomes, muscle strength, and peak oxygen
      consumption at the 4-month and 1 year follow-up, and over time (1-year).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: Knee-related quality of life
time frame: 1 year
description: Primary outcome for the study will be the quality of life subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS) (0-100 scale). 0 is very poor knee-related quality of life, while 100 indicates normal knee-related quality of life.
measure: Knee function
time frame: 4 months and 1 year
description: The KOOS is a self-administered knee-specific questionnaire containing 5-item Likert scales on pain, other symptoms, activities of daily living (ADL), function in sports and recreation and knee-related quality of life (QOL). Each scale goes from 0-100, 0 indicating worse function and 100 representing normal function.
measure: Health-related quality of life
time frame: 4 months and 1 year
description: Euro Quality of life 5 dimensions 5 level (EQ-5D-5L) will be used to measure health related quality of life. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EuroQol (EQ) Visual analogue scale (VAS) records the patient's self-rated health on a vertical visual analogue scale. This can be used as a quantitative measure of health outcome that reflects the patient's own judgement. The scores on these five dimensions can be presented as a health profile or can be converted to a single summary index number (utility) reflecting preferability compared to other health profiles.
measure: Radiographic osteoarthritis progression
time frame: 2 years
description: Conventional x-rays will be used to assess radiographic progression of osteoarthritis
measure: Isokinetic muscle strength
time frame: 4 months and 1 year
description: Isokinetic muscle strength will be measured in a Biodex6000 machine. The participants sit in a standardised position and flex/extend their knees at 60 degrees/second. The peak torque value of the five repetitions is recorded.
measure: Maximal oxygen consumption (VO2max)
time frame: 4 months and 1 year
description: VO2max is measured using an incremental ramp test procedure on a stationary bike, designed to achieve supramaximal workloads within ~4-6 min. The workload was increased by 25 watts every 30 second to total exhaustion.
measure: Self-efficacy for pain
time frame: 4 months and 1 year
description: Arthritis self-efficacy scale (ASES) was included to measure self-efficacy for pain. A modified version of ASES containing 11 questions regarding the patient's certainty to perform various tasks related to pain and symptoms, where each item is rated from 1 (very uncertain) to 5 (very certain) was used.
measure: Total knee replacement
time frame: 5 years
description: We will register continuously numbers of total knee replacements during the follow-up years.
arm group label: Strength training
arm group type: Experimental
description: The strength group include progressive strength training and neuromuscular exercises. The inclusion will be performed 2-3 times a week for 12 weeks.
arm group label: Aerobic exercise
arm group type: Experimental
description: The aerobic exercise group will cycle on an ergometer bicycle 2-3 times a week for 12 weeks on moderate loading. The loading will be controlled by a heart rate monitor and is defined as 75% of maximal heart rate (calculated with formula for maximal heart rate reserve).
arm group label: Control group
arm group type: No Intervention
description: The control group will do as usual.
intervention type: Other
intervention name: Strength training
description: The strength training will be delivered 2-3 times per week for 12 weeks, 5-8 repetitions maximum in 3 series. The patients must warm up 5 minutes on an ergometer cycle. The following muscle groups will be trained: Quadriceps and hamstrings, hip muscles (abductors and extensors), calf muscles. A home exercise program will be delivered including one leg exercises and balance exercises. Progression will follow a 2+ principle. For instance, when the study participant is able to perform 2 more repetitions, more loads are required.
arm group label: Strength training
intervention type: Other
intervention name: Aerobic exercise
description: The aerobic exercise program include ergometer cycling for at least 45 minutes 2-3 times a week on 75-80% of max heart rate will be required.
arm group label: Aerobic exercise
criteria: 
gender: All
minimum age: 35 Years
maximum age: 70 Years
healthy volunteers: No
last name: May Arna Risberg, PhD
role: Study Chair
affiliation: Oslo University Hospital
facility: 
country: Norway
responsible party type: Principal Investigator
investigator affiliation: Oslo University Hospital
investigator full name: Britt Elin Øiestad
investigator title: Principal Investigator
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
sharing ipd: No
provided document: 