<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/NCT03806387</url>
  </required_header>
  <id_info>
    <org_study_id>MS_Improve</org_study_id>
    <nct_id>NCT03806387</nct_id>
  </id_info>
  <brief_title>Physical and Cognitive Performance During the Two First Years of Lemtrada Treatment</brief_title>
  <official_title>Physical and Cognitive Performance During the Two First Years of Lemtrada Treatment - a Prospective Observational Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genzyme, a Sanofi Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</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>
      Multiple Sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central&#xD;
      nervous system (CNS). The symptoms of MS are wide-ranging, but patients perceive loss of&#xD;
      physical function (gait) and cognitive function as the most critical consequences of the&#xD;
      disease. Moreover, recent studies have shown that already at early disease stages functional&#xD;
      impairments are present.&#xD;
&#xD;
      One of the more recent approved medical treatments for MS patients is Alemtuzumab (product&#xD;
      name Lemtrada), a humanized monoclonal antibody targeting CD52 cells, that depletes and&#xD;
      repopulates B lymphocytes and T lymphocytes, causing sustained changes in the adaptive&#xD;
      immunity. In 2013 and 2014 Alemtuzumab was approved in EU and USA, respectively.&#xD;
&#xD;
      With the exception of the MS Functional Composite z-score, the previous clinical studies&#xD;
      investigating the effect of Alemtuzumab have exclusively focused on clinical parameters such&#xD;
      as MRI indications of disease activity (accumulation of lesion, total and regional brain&#xD;
      atrophy etc.), relapse-rates, changes in 'expanded disability status scale' (EDSS) and&#xD;
      side-effects/adverse events. However, no previous studies have performed in depth monitoring&#xD;
      on how physical or cognitive performance are affected following initiation of treatment with&#xD;
      Alemtuzumab despite the paramount importance to patients.&#xD;
&#xD;
      The primary purpose of this project is to monitor the changes in physical performance during&#xD;
      the first two years of treatment with Alemtuzumab in a well characterised Danish cohort of&#xD;
      people with relapsing-remitting MS. A secondary purpose is to monitor the impact of&#xD;
      Alemtuzumab treatment on cognition during the first two years of treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">June 30, 2021</completion_date>
  <primary_completion_date type="Actual">July 30, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Six minute walking test (6MWT)</measure>
    <time_frame>From baseline to 24 months</time_frame>
    <description>Change in maximal walking distance covered in 6 minutes</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Six minute walking test (6MWT)</measure>
    <time_frame>From baseline to 3 months, 6 months, and 12 months</time_frame>
    <description>Change in maximal walking distance covered in 6 minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Timed 25 foot walk (T25FWT)</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in maximal walking speed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>5 times sit to stand test (5STS)</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in time to perform 5 times sit to stand test (5STS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Timed Up and Go (TUG)</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in time to perform Timed Up and Go (TUG)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stair Climbing test</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in time to perform 9-step stair climbing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Six Spot Step Test (SSST)</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in maximal walking speed while challenging coordination/balance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximal oxygen uptake (VO2 max)</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in aerobic power</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximal muscle strength</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in isometric and dynamic knee extensor muscle strength, isometric hand grip strength</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuromuscular activation</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in neural drive during maximal isometric knee extension</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body composition - limb lean mass</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in total lower limb lean mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body composition - limb fat mass</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in total lower limb fat mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body composition - whole body lean mass</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in total body lean mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body composition - whole body fat mass</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in total body fat mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Selective Reminding Test (SRT)</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in cognitive test assessing memory</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symbol Digit Modalities Test (SDMT)</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in cognitive test assessing processing speed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical activity</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Change in accelerometer-based assessment of 24-hour physical activity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Severity of Disease</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Estimation of disease severity by the Expanded Disability Severity Scale (EDSS scores: best 0 = normal neurological exam, worst 10 = death due to multiple sclerosis)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse frequency</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Number of relapses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>12-item Multiple Sclerosis Walking Scale (MSWS-12)</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Self-reported questionnaire assessing impact of MS on walking ability (MSWS-12 scores: best 0, worst 100)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Fatigue Impact Scale (MFIS)</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Self-reported questionnaire assessing impact of MS-induced fatigue on a persons life (MFIS total scores: best 0, worst 84; physical subscale scores: best 0, worst 36; cognitive subscale scores: best 0, worst 40; psychosocial subscale scores: best 0, worst 8)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiple Sclerosis Impact Scale (MSIS-29)</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Self-reported questionnaire assessing impact of MS on day-to-day life, from a physical perspective (MSIS-29 physical scale: best 0, worst 100 (greater impact of disease on daily function = worse health) and from a psychological perspective (MSIS-29 psychological scale: best 0, worst 100 (greater impact of disease on daily function = worse health)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Anxiety and Depression Scale (HADS)</measure>
    <time_frame>From baseline to 3 months, 6 months, 12 months, and 24 months</time_frame>
    <description>Self-reported questionnaire assessing impact of MS on anxiety (scores: best 0, worst 21) and depression (scores: best 0, worst 21)</description>
  </secondary_outcome>
  <enrollment type="Actual">17</enrollment>
  <condition>Multiple Sclerosis</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alemtuzumab</intervention_name>
    <description>Alemtuzumab will be given two times, separated by 1 year.</description>
    <other_name>Lemtrada</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Multiple Sclerosis patients will be recruited from MS clinics all over Denmark.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical definite Multiple Sclerosis diagnosis according to the McDonald criteria&#xD;
&#xD;
          -  About to commence alemtuzumab (Lemtrada) treatment&#xD;
&#xD;
          -  Expanded Disability Status Scale (EDSS) ≤ 5.5&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Co-morbidities that prevent participation in the project (dementia, serious cognitive&#xD;
             disorders etc.)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ulrik Dalgas, MSc,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aarhus University, Health, Section for Sport Science</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aarhus University, Health, Section for Sport Science</name>
      <address>
        <city>Aarhus</city>
        <state>Jutland</state>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>August 31, 2023</last_update_submitted>
  <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 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>Multiple Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alemtuzumab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03806387
org study id: MS_Improve
nct id: NCT03806387
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Multiple Sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central
      nervous system (CNS). The symptoms of MS are wide-ranging, but patients perceive loss of
      physical function (gait) and cognitive function as the most critical consequences of the
      disease. Moreover, recent studies have shown that already at early disease stages functional
      impairments are present.

      One of the more recent approved medical treatments for MS patients is Alemtuzumab (product
      name Lemtrada), a humanized monoclonal antibody targeting CD52 cells, that depletes and
      repopulates B lymphocytes and T lymphocytes, causing sustained changes in the adaptive
      immunity. In 2013 and 2014 Alemtuzumab was approved in EU and USA, respectively.

      With the exception of the MS Functional Composite z-score, the previous clinical studies
      investigating the effect of Alemtuzumab have exclusively focused on clinical parameters such
      as MRI indications of disease activity (accumulation of lesion, total and regional brain
      atrophy etc.), relapse-rates, changes in 'expanded disability status scale' (EDSS) and
      side-effects/adverse events. However, no previous studies have performed in depth monitoring
      on how physical or cognitive performance are affected following initiation of treatment with
      Alemtuzumab despite the paramount importance to patients.

      The primary purpose of this project is to monitor the changes in physical performance during
      the first two years of treatment with Alemtuzumab in a well characterised Danish cohort of
      people with relapsing-remitting MS. A secondary purpose is to monitor the impact of
      Alemtuzumab treatment on cognition during the first two years of treatment.
observational model: Cohort
time perspective: Prospective
measure: Six minute walking test (6MWT)
time frame: From baseline to 24 months
description: Change in maximal walking distance covered in 6 minutes
measure: Six minute walking test (6MWT)
time frame: From baseline to 3 months, 6 months, and 12 months
description: Change in maximal walking distance covered in 6 minutes
measure: Timed 25 foot walk (T25FWT)
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in maximal walking speed
measure: 5 times sit to stand test (5STS)
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in time to perform 5 times sit to stand test (5STS)
measure: Timed Up and Go (TUG)
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in time to perform Timed Up and Go (TUG)
measure: Stair Climbing test
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in time to perform 9-step stair climbing
measure: Six Spot Step Test (SSST)
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in maximal walking speed while challenging coordination/balance
measure: Maximal oxygen uptake (VO2 max)
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in aerobic power
measure: Maximal muscle strength
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in isometric and dynamic knee extensor muscle strength, isometric hand grip strength
measure: Neuromuscular activation
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in neural drive during maximal isometric knee extension
measure: Body composition - limb lean mass
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in total lower limb lean mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan).
measure: Body composition - limb fat mass
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in total lower limb fat mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan).
measure: Body composition - whole body lean mass
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in total body lean mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan).
measure: Body composition - whole body fat mass
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in total body fat mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan).
measure: Selective Reminding Test (SRT)
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in cognitive test assessing memory
measure: Symbol Digit Modalities Test (SDMT)
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in cognitive test assessing processing speed
measure: Physical activity
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Change in accelerometer-based assessment of 24-hour physical activity
measure: Clinical Severity of Disease
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Estimation of disease severity by the Expanded Disability Severity Scale (EDSS scores: best 0 = normal neurological exam, worst 10 = death due to multiple sclerosis)
measure: Relapse frequency
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Number of relapses
measure: 12-item Multiple Sclerosis Walking Scale (MSWS-12)
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Self-reported questionnaire assessing impact of MS on walking ability (MSWS-12 scores: best 0, worst 100)
measure: Modified Fatigue Impact Scale (MFIS)
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Self-reported questionnaire assessing impact of MS-induced fatigue on a persons life (MFIS total scores: best 0, worst 84; physical subscale scores: best 0, worst 36; cognitive subscale scores: best 0, worst 40; psychosocial subscale scores: best 0, worst 8)
measure: Multiple Sclerosis Impact Scale (MSIS-29)
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Self-reported questionnaire assessing impact of MS on day-to-day life, from a physical perspective (MSIS-29 physical scale: best 0, worst 100 (greater impact of disease on daily function = worse health) and from a psychological perspective (MSIS-29 psychological scale: best 0, worst 100 (greater impact of disease on daily function = worse health)
measure: Hospital Anxiety and Depression Scale (HADS)
time frame: From baseline to 3 months, 6 months, 12 months, and 24 months
description: Self-reported questionnaire assessing impact of MS on anxiety (scores: best 0, worst 21) and depression (scores: best 0, worst 21)
intervention type: Drug
intervention name: Alemtuzumab
description: Alemtuzumab will be given two times, separated by 1 year.
other name: Lemtrada
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Ulrik Dalgas, MSc,PhD
role: Principal Investigator
affiliation: Aarhus University, Health, Section for Sport Science
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Alemtuzumab