<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/NCT02236624</url>
  </required_header>
  <id_info>
    <org_study_id>Avonex</org_study_id>
    <nct_id>NCT02236624</nct_id>
  </id_info>
  <brief_title>Aerobic Exercise and Flu-like Symptoms Following Interferon Beta 1a Injections in Patients With Multiple Sclerosis?</brief_title>
  <official_title>Can Aerobic Exercise Reduce Flu-like Symptoms Following Interferon Beta 1a Injections in Patients With Multiple Sclerosis?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Aarhus University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>MS-Clinic of Southern Jutland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>MS-Clinic Viborg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>MS-Clinic Odense</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Biogen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Aarhus</source>
  <brief_summary>
    <textblock>
      The purpose of the present study is to test the hypothesis that aerobic training can reduce&#xD;
      flu-like symptoms following interferon beta 1a injections in patients with Multiple&#xD;
      Sclerosis.&#xD;
&#xD;
      A secondary purpose is to evaluate whether or not changes in circulating cytokines provide a&#xD;
      mechanism that can explain a potential positive effect.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Flu-like symptoms (FLS) such as fever, muscle aches, chills, and fatigue are common side&#xD;
      effects of interferon beta (IFN-ß) treatment and may affect the willingness of patients with&#xD;
      multiple sclerosis (MS) to initiate therapy. The initiation phase of MS treatment is a&#xD;
      critical period that can affect patients' views on the long-term acceptability and the&#xD;
      adherence to the therapy, underscoring the need for strategies to reduce treatment-related&#xD;
      adverse events such as FLS following IFN-ß injections.&#xD;
&#xD;
      Once-weekly intramuscular IFNß-1a, which has been available since 1996, is indicated for the&#xD;
      treatment of patients with relapsing forms of MS to slow the accumulation of physical&#xD;
      disability progression and the frequency of clinical exacerbations. Although intramuscular&#xD;
      IFNß-1a is generally well tolerated, FLS have been reported in up to 76% of patients&#xD;
      receiving this treatment. Consequently, interventions that can reduce FLS after IFNß-1a&#xD;
      injection are warranted. One approach to reduce FLS has been dose titration. Titration is the&#xD;
      practice of initiating therapy with a lower starting dose and gradually increasing the dose&#xD;
      at defined intervals until the full dose is reached. Moreover, a combination of dose&#xD;
      titration and pre-treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or&#xD;
      acetaminophen in healthy subjects, has been sown to reduce FLS severity by 37-76%. However,&#xD;
      not all patients benefit from dose titration and also the effects in MS still have to be&#xD;
      determined. Consequently, other types of FLS management after IFNß-1a injection have to be&#xD;
      determined.&#xD;
&#xD;
      Interestingly, case reports from both Finland and Denmark suggest that aerobic exercise is&#xD;
      able to markedly reduce FLS symptoms in MS patients, but so far no studies have evaluated&#xD;
      this. However, from healthy subjects it is known that aerobic exercise is capable of&#xD;
      positively influencing the immune system and evidence suggests that the prophylactic effect&#xD;
      of exercise may, to some extent, be the induction of an anti-inflammatory environment with&#xD;
      each bout of exercise (e.g. via increases in circulating anti-inflammatory cytokines&#xD;
      including interleukin (IL)-1 receptor antagonist and IL-10).&#xD;
&#xD;
      The existing evidence is particularly suggestive of an acute effect of aerobic exercise on&#xD;
      the circulating cytokine levels, which could be an important mechanism in explaining a&#xD;
      potential positive effect of aerobic exercise on FLS.&#xD;
&#xD;
      Consequently, the purpose of the present study is to test the hypothesis that aerobic&#xD;
      training can reduce FLS following interferon beta 1a injections in patients with Multiple&#xD;
      Sclerosis.&#xD;
&#xD;
      A secondary purpose is to evaluate whether or not changes in circulating cytokines provide a&#xD;
      mechanism that can explain a potential positive effect.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2014</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">February 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Flu-like symptoms assessment</measure>
    <time_frame>Change from baseline to 24 hours.</time_frame>
    <description>Comparison of the mean relative change in flu-like symptoms severity from pre-injection to 5 hours post-injection. At 12h and 24h post intervention the participants will further register flu-like symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bloodbourne biomarkers</measure>
    <time_frame>Baseline to 24h</time_frame>
    <description>Bloodbourne biomarkers: Cytokines</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Aerobic Exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Aerobic exercise</intervention_name>
    <arm_group_label>Aerobic Exercise</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Definite relapsing-remitting MS according to the McDonald criteria&#xD;
&#xD;
          -  Treated with IFNß-1a (Avonex®) for at least 6 months&#xD;
&#xD;
          -  Frequent experiencing FLS (muscle aches, chills, fatigue, fewer9) in the hours&#xD;
             following IFNß-1a injection (self-reporting that this happens 75% or more of the times&#xD;
             after injection).&#xD;
&#xD;
          -  Female subjects of childbearing potential are required to practice effective&#xD;
             contraception during the study and to continue contraception for 30 days after their&#xD;
             last dose of study treatment.&#xD;
&#xD;
          -  Expected to be able to complete the aerobic exercise intervention&#xD;
&#xD;
          -  Willingly to transport themselves to the exercise/testing facility&#xD;
&#xD;
          -  Give informed consent&#xD;
&#xD;
          -  Age above 18 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have FLS (i.e. muscle aches, chills, fatigue or fewer) or serious infection within a&#xD;
             24h period prior to the screening. Patients having chronic FLS or infection will,&#xD;
             therefore, be excluded. This will be tested by patient interview and, if required,&#xD;
             further examination&#xD;
&#xD;
          -  Have a known history or positive test result for hepatitis B, hepatitis C, or HIV&#xD;
&#xD;
          -  Use beta-blockers.&#xD;
&#xD;
          -  Have clinically significant abnormality in laboratory or electrocardiogram measures,&#xD;
             chronic fatigue syndrome or fibromyalgia, pre-malignant disease, or malignant disease&#xD;
&#xD;
          -  Have had allergy shot or desensitization therapy within 1 month of day 1&#xD;
             (randomization) vaccination within 2 weeks of day 1.&#xD;
&#xD;
          -  Stop taking IFNß-1a.&#xD;
&#xD;
          -  Are pregnant.&#xD;
&#xD;
          -  Suffer from dementia, alcohol abuse or have a pacemaker.&#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>Martin Langeskov-Christensen, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sport Science, Department of Public Health, Aarhus University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ulrik Dalgas, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Sport Science, Department of Public Health, Aarhus University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Egon Stenager, Dr.med.</last_name>
    <role>Study Chair</role>
    <affiliation>MS-Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Department of Neurology, Sønderborg, Denmark and Institute of Regional Health Services, University of Southern Denmark.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Thor Petersen, Dr.med.</last_name>
    <role>Study Chair</role>
    <affiliation>MS-Clinic Aarhus, Department of Neurology, Aarhus University Hospital, Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sport Science, Department of Public Health, Aarhus University</name>
      <address>
        <city>Aarhus</city>
        <state>Aarhus C</state>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>September 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <last_update_submitted>April 18, 2016</last_update_submitted>
  <last_update_submitted_qc>April 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 19, 2016</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>
    <mesh_term>Sclerosis</mesh_term>
  </condition_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/NCT02236624
org study id: Avonex
nct id: NCT02236624
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
The purpose of the present study is to test the hypothesis that aerobic training can reduce
      flu-like symptoms following interferon beta 1a injections in patients with Multiple
      Sclerosis.

      A secondary purpose is to evaluate whether or not changes in circulating cytokines provide a
      mechanism that can explain a potential positive effect.
Flu-like symptoms (FLS) such as fever, muscle aches, chills, and fatigue are common side
      effects of interferon beta (IFN-ß) treatment and may affect the willingness of patients with
      multiple sclerosis (MS) to initiate therapy. The initiation phase of MS treatment is a
      critical period that can affect patients' views on the long-term acceptability and the
      adherence to the therapy, underscoring the need for strategies to reduce treatment-related
      adverse events such as FLS following IFN-ß injections.

      Once-weekly intramuscular IFNß-1a, which has been available since 1996, is indicated for the
      treatment of patients with relapsing forms of MS to slow the accumulation of physical
      disability progression and the frequency of clinical exacerbations. Although intramuscular
      IFNß-1a is generally well tolerated, FLS have been reported in up to 76% of patients
      receiving this treatment. Consequently, interventions that can reduce FLS after IFNß-1a
      injection are warranted. One approach to reduce FLS has been dose titration. Titration is the
      practice of initiating therapy with a lower starting dose and gradually increasing the dose
      at defined intervals until the full dose is reached. Moreover, a combination of dose
      titration and pre-treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or
      acetaminophen in healthy subjects, has been sown to reduce FLS severity by 37-76%. However,
      not all patients benefit from dose titration and also the effects in MS still have to be
      determined. Consequently, other types of FLS management after IFNß-1a injection have to be
      determined.

      Interestingly, case reports from both Finland and Denmark suggest that aerobic exercise is
      able to markedly reduce FLS symptoms in MS patients, but so far no studies have evaluated
      this. However, from healthy subjects it is known that aerobic exercise is capable of
      positively influencing the immune system and evidence suggests that the prophylactic effect
      of exercise may, to some extent, be the induction of an anti-inflammatory environment with
      each bout of exercise (e.g. via increases in circulating anti-inflammatory cytokines
      including interleukin (IL)-1 receptor antagonist and IL-10).

      The existing evidence is particularly suggestive of an acute effect of aerobic exercise on
      the circulating cytokine levels, which could be an important mechanism in explaining a
      potential positive effect of aerobic exercise on FLS.

      Consequently, the purpose of the present study is to test the hypothesis that aerobic
      training can reduce FLS following interferon beta 1a injections in patients with Multiple
      Sclerosis.

      A secondary purpose is to evaluate whether or not changes in circulating cytokines provide a
      mechanism that can explain a potential positive effect.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Flu-like symptoms assessment
time frame: Change from baseline to 24 hours.
description: Comparison of the mean relative change in flu-like symptoms severity from pre-injection to 5 hours post-injection. At 12h and 24h post intervention the participants will further register flu-like symptoms.
measure: Bloodbourne biomarkers
time frame: Baseline to 24h
description: Bloodbourne biomarkers: Cytokines
arm group label: Aerobic Exercise
arm group type: Experimental
intervention type: Behavioral
intervention name: Aerobic exercise
arm group label: Aerobic Exercise
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Martin Langeskov-Christensen, MSc
role: Principal Investigator
affiliation: Sport Science, Department of Public Health, Aarhus University
last name: Ulrik Dalgas, PhD
role: Study Chair
affiliation: Sport Science, Department of Public Health, Aarhus University
last name: Egon Stenager, Dr.med.
role: Study Chair
affiliation: MS-Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Department of Neurology, Sønderborg, Denmark and Institute of Regional Health Services, University of Southern Denmark.
last name: Thor Petersen, Dr.med.
role: Study Chair
affiliation: MS-Clinic Aarhus, Department of Neurology, Aarhus University Hospital, Denmark
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Sclerosis