<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/NCT03824938</url>
  </required_header>
  <id_info>
    <org_study_id>AAAS2529</org_study_id>
    <secondary_id>1R21HD091836-01A1</secondary_id>
    <nct_id>NCT03824938</nct_id>
  </id_info>
  <brief_title>Aspirin for Exercise in Multiple Sclerosis (ASPIRE)</brief_title>
  <acronym>ASPIRE</acronym>
  <official_title>Aspirin for Exercise in Multiple Sclerosis (ASPIRE): A Double-Blind RCT of Aspirin or Acetaminophen Pretreatment to Improve Exercise Performance in Multiple Sclerosis (MS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study investigates the use of aspirin as an exercise pre-treatment to reduce overheating&#xD;
      and exhaustion, which may potentially allow many more people with multiple sclerosis to&#xD;
      participate in and benefit from exercise. The design is double-blind, within-subject, with&#xD;
      three arms: participants will receive one of three treatments at three separate study visits:&#xD;
      aspirin, acetaminophen, and placebo, followed by completion of a maximal exercise test.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Persons with multiple sclerosis benefit from exercise, but many avoid it because of&#xD;
      exhaustion and overheating. This randomized controlled trial (RCT) tests aspirin as a method&#xD;
      to increase time to exhaustion for persons with MS, through its antipyretic mechanism.&#xD;
      Participants will be seen at our laboratory for maximal exercise tests on three separate&#xD;
      days. At each session, they will be given one of three treatments: aspirin, acetaminophen (a&#xD;
      drug that is anti-inflammatory but not antipyretic, thereby allowing for isolation of the&#xD;
      antipyretic action of aspirin), and placebo. Primary outcome is increased time to exhaustion,&#xD;
      secondary outcome is reduced body temperature increase during exercise.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 30, 2019</start_date>
  <completion_date type="Actual">February 28, 2022</completion_date>
  <primary_completion_date type="Actual">February 28, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>This is a within-subject design double-blind RCT in which each participant receives 1 of 3 treatments at 3 timepoints (i.e., 3 separate days separated by 1-week washout periods).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Study biostatistician will derive the randomization schedule. Study pharmacy will make assignments and maintain blinding until data analysis is complete for the full sample.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Time-to-exhaustion</measure>
    <time_frame>from start of exercise test until self-reported exhaustion, up to 30 minutes</time_frame>
    <description>Duration of time exercising before reaching peak exertion, defined as cadence drop below 40 revolutions per minute (RPM) for &gt;/= 5 seconds, or patient reaches volitional exhaustion in accordance with American Thoracic Society standard test termination criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Exercise-induced body temperature increase</measure>
    <time_frame>from start of exercise test until self-reported exhaustion, up to 30 minutes</time_frame>
    <description>Change in body temperature from pre- to post- maximal exercise test</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Aspirin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aspirin 650 mg capsule by mouth, single dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Acetaminophen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Acetaminophen 650 mg capsule by mouth, single dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo 650 mg capsule by mouth, single dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin 650mg Oral Capsule</intervention_name>
    <description>A 650mg dose of aspirin is administered in the laboratory one hour before participant completes a maximal exercise test.</description>
    <arm_group_label>Aspirin</arm_group_label>
    <other_name>Aspirin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetaminophen Tablet 650mg</intervention_name>
    <description>A 650mg dose of acetaminophen is administered in the laboratory one hour before participant completes a maximal exercise test.</description>
    <arm_group_label>Acetaminophen</arm_group_label>
    <other_name>Acetaminophen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>A placebo pill is administered in the laboratory one hour before participant completes a maximal exercise test.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of relapsing-remitting MS&#xD;
&#xD;
          -  self-reported heat-sensitivity to exercise&#xD;
&#xD;
          -  Expanded Disability Status Scale (EDSS) total score ≤ 6.0&#xD;
&#xD;
          -  exacerbation-free (and no use of corticosteroids) for 6 weeks prior&#xD;
&#xD;
          -  BMI ≤ 40&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  prior history of significant head injury, stroke, or other neurological&#xD;
             disease/disorder&#xD;
&#xD;
          -  current daily use of antipyretics or pain medication&#xD;
&#xD;
          -  currently in a major depressive episode&#xD;
&#xD;
          -  vascular disease of the legs, uncontrolled high blood pressure&#xD;
&#xD;
          -  uncontrolled diabetes mellitus or problem with blood sugar levels&#xD;
&#xD;
          -  contraindications to aspirin use (history of confirmed peptic ulcer, gastrointestinal&#xD;
             or severe gynecological bleeding)&#xD;
&#xD;
          -  tarry stool or known fecal occult blood&#xD;
&#xD;
          -  uncontrolled syndrome of asthma, rhinitis, or nasal polyps&#xD;
&#xD;
          -  contraindications to acetaminophen use (severe active hepatic disease, Hepatitis C&#xD;
             Virus)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Victoria M Leavitt, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University Irving Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Leavitt VM, Blanchard AR, Guo CY, Gelernt E, Sumowski JF, Stein J. Aspirin is an effective pretreatment for exercise in multiple sclerosis: A double-blind randomized controlled pilot trial. Mult Scler. 2018 Oct;24(11):1511-1513. doi: 10.1177/1352458517739138. Epub 2017 Oct 27.</citation>
    <PMID>29076760</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <last_update_submitted>September 13, 2022</last_update_submitted>
  <last_update_submitted_qc>September 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>Victoria M. Leavitt</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>exercise</keyword>
  <keyword>aspirin</keyword>
  <keyword>cooling</keyword>
  <keyword>antipyretic</keyword>
  <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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Acetaminophen</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Raw data for primary and secondary outcomes will be shared with qualified researchers upon reasonable request to study PI.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Data will be available from close of the study until 2031.</ipd_time_frame>
    <ipd_access_criteria>Qualified researchers, upon request to study PI</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 21, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/38/NCT03824938/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>February 14, 2023</submitted>
    <returned>March 10, 2023</returned>
  </pending_results>
  <!-- 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/NCT03824938
org study id: AAAS2529
secondary id: 1R21HD091836-01A1
nct id: NCT03824938
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study investigates the use of aspirin as an exercise pre-treatment to reduce overheating
      and exhaustion, which may potentially allow many more people with multiple sclerosis to
      participate in and benefit from exercise. The design is double-blind, within-subject, with
      three arms: participants will receive one of three treatments at three separate study visits:
      aspirin, acetaminophen, and placebo, followed by completion of a maximal exercise test.
Persons with multiple sclerosis benefit from exercise, but many avoid it because of
      exhaustion and overheating. This randomized controlled trial (RCT) tests aspirin as a method
      to increase time to exhaustion for persons with MS, through its antipyretic mechanism.
      Participants will be seen at our laboratory for maximal exercise tests on three separate
      days. At each session, they will be given one of three treatments: aspirin, acetaminophen (a
      drug that is anti-inflammatory but not antipyretic, thereby allowing for isolation of the
      antipyretic action of aspirin), and placebo. Primary outcome is increased time to exhaustion,
      secondary outcome is reduced body temperature increase during exercise.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This is a within-subject design double-blind RCT in which each participant receives 1 of 3 treatments at 3 timepoints (i.e., 3 separate days separated by 1-week washout periods).
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Study biostatistician will derive the randomization schedule. Study pharmacy will make assignments and maintain blinding until data analysis is complete for the full sample.
measure: Time-to-exhaustion
time frame: from start of exercise test until self-reported exhaustion, up to 30 minutes
description: Duration of time exercising before reaching peak exertion, defined as cadence drop below 40 revolutions per minute (RPM) for >/= 5 seconds, or patient reaches volitional exhaustion in accordance with American Thoracic Society standard test termination criteria.
measure: Exercise-induced body temperature increase
time frame: from start of exercise test until self-reported exhaustion, up to 30 minutes
description: Change in body temperature from pre- to post- maximal exercise test
arm group label: Aspirin
arm group type: Experimental
description: Aspirin 650 mg capsule by mouth, single dose
arm group label: Acetaminophen
arm group type: Active Comparator
description: Acetaminophen 650 mg capsule by mouth, single dose
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo 650 mg capsule by mouth, single dose
intervention type: Drug
intervention name: Aspirin 650mg Oral Capsule
description: A 650mg dose of aspirin is administered in the laboratory one hour before participant completes a maximal exercise test.
arm group label: Aspirin
other name: Aspirin
intervention type: Drug
intervention name: Acetaminophen Tablet 650mg
description: A 650mg dose of acetaminophen is administered in the laboratory one hour before participant completes a maximal exercise test.
arm group label: Acetaminophen
other name: Acetaminophen
intervention type: Other
intervention name: Placebo
description: A placebo pill is administered in the laboratory one hour before participant completes a maximal exercise test.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Victoria M Leavitt, PhD
role: Principal Investigator
affiliation: Columbia University
facility: 
country: United States
citation: Leavitt VM, Blanchard AR, Guo CY, Gelernt E, Sumowski JF, Stein J. Aspirin is an effective pretreatment for exercise in multiple sclerosis: A double-blind randomized controlled pilot trial. Mult Scler. 2018 Oct;24(11):1511-1513. doi: 10.1177/1352458517739138. Epub 2017 Oct 27.
PMID: 29076760
responsible party type: Principal Investigator
investigator affiliation: Columbia University
investigator full name: Victoria M. Leavitt
investigator title: Assistant Professor
mesh term: Multiple Sclerosis
mesh term: Sclerosis
mesh term: Aspirin
mesh term: Acetaminophen
sharing ipd: Yes
ipd description: Raw data for primary and secondary outcomes will be shared with qualified researchers upon reasonable request to study PI.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Data will be available from close of the study until 2031.
ipd access criteria: Qualified researchers, upon request to study PI
provided document: 
submitted: February 14, 2023
returned: March 10, 2023