<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/NCT04441619</url>
  </required_header>
  <id_info>
    <org_study_id>IRB20190295 3-N</org_study_id>
    <secondary_id>R01AR073745-01A1</secondary_id>
    <nct_id>NCT04441619</nct_id>
  </id_info>
  <brief_title>Mechanisms and Modulation of Pain Modulatory Capacity</brief_title>
  <official_title>Mechanisms and Modulation of Pain Modulatory Capacity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Florida</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This project proposes to understand the sources of pain variability, and demonstrate that&#xD;
      pain variability represents fluctuation in natural pain management. The project further&#xD;
      proposes to determine if endogenous capacity to modulate pain can be trained to maximize&#xD;
      their body's ability to manage pain, much as the way in which athletic performance can be&#xD;
      trained.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Many physiological systems (bioenergy, immune etc.) involve feedback mechanisms to respond to&#xD;
      challenges, with increased output or capacity for adaptive change. A similar process is&#xD;
      plausible for pain modulation where previous successful pain experience and resolution&#xD;
      suggests a pain modulatory system with adaptive capacity. The proposed research examines how&#xD;
      a musculoskeletal training program modulates pain response in people with fibromyalgia&#xD;
      compared to healthy individuals. Previous research suggests that moderate-high level exercise&#xD;
      is associated with attenuation of pain sensitivity and clinical pain intensity in healthy&#xD;
      individuals. The proposal seeks to extend findings from previous research and examine how&#xD;
      repeated exposure and subsequent adaptations to musculoskeletal pain over time influence pain&#xD;
      modulation (PMC). The first outcome is that people with fibromyalgia (FM) will have PMC&#xD;
      trainability similar to asymptomatic controls, with the obvious implications for clinical&#xD;
      application. The second outcome is that FM patients will demonstrate a deficit in PMC&#xD;
      trainability. This outcome will represent an important diagnostic sign, and guide research to&#xD;
      additional mechanistic investigation. The third outcome is that impaired or lessened PMC&#xD;
      trainability is evident in FM patients and this variability can be explored as an individual&#xD;
      difference with clinical implications. The theoretical fourth potential outcome is&#xD;
      sensitization in FM patients, however pilot data show that DOMS resolves within the same&#xD;
      relative time window as controls. Though not hypothesized, the data and design will allow for&#xD;
      examination of this possibility. One potential conclusion from these projects could be that&#xD;
      FM arises from an inability to enter a recovery period within which PMC could adapt and&#xD;
      increase resilience. The proposal will be able to address at least some of the potential for&#xD;
      this inability to recover.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 30, 2020</start_date>
  <completion_date type="Anticipated">April 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2024</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>
    <intervention_model_description>This is a mechanistic observational study</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Assessments will be performed by an investigator who is not aware of the group assignment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in pain intensity</measure>
    <time_frame>Baseline up to 10 weeks</time_frame>
    <description>Pain during movement and pain at rest using the visual analog scale (VAS). Scores are recorded every day by making a handwritten mark on a 10-cm line that represents a continuum between &quot;no pain&quot; and &quot;worst pain.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in thermal quantitative sensory testing</measure>
    <time_frame>Baseline up to 10 weeks</time_frame>
    <description>Thermal pain thresholds and suprathreshold responses will be collected using a numeric rating scale anchored 0 &quot;no pain&quot; and 10 &quot;worst pain imaginable&quot;. Change will be calculated using simple change scores and more complex multi-level modeling.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in pressure quantitative sensory testing</measure>
    <time_frame>Baseline up to 10 weeks</time_frame>
    <description>Pressure pain threshold will be collected using a numeric rating scale anchored 0 &quot;no pain&quot; and 10 &quot;worst pain imaginable&quot;. Change will be calculated using simple change scores and more complex multi-level modeling.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cortical network connectivity</measure>
    <time_frame>Baseline up to 10 weeks</time_frame>
    <description>Functional magnetic resonance imaging of regional connectivity among pain-related brain regions</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">180</enrollment>
  <condition>Musculoskeletal Pain</condition>
  <arm_group>
    <arm_group_label>Repeated exposure</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will complete four exercise sessions designed to induce delayed onset muscle soreness in the biceps</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single exposure</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will complete one exercise session designed to induce delayed onset muscle soreness</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Natural history</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants will complete all sensory testing and imaging but not perform any exercise sessions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Delayed onset muscle soreness.</intervention_name>
    <description>Participants will perform a fatiguing exercise protocol for the upper extremity (biceps muscles)</description>
    <arm_group_label>Repeated exposure</arm_group_label>
    <arm_group_label>Single exposure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Asymptomatic people (ie no current pain conditions)&#xD;
&#xD;
          -  Participants with widespread muscle pain (WMP) aged 18 years of age and older&#xD;
&#xD;
          -  Participants with WMP must meet the ACR (2010) diagnostic criteria of multiple regions&#xD;
             of muscle pain&#xD;
&#xD;
          -  The asymptomatic group will be free of current wrist/hand, elbow, or shoulder pain and&#xD;
             chronic pain conditions (eg irritable bowel syndrome, FM)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participation in a conditioning program specific to the biceps in the past 6 months&#xD;
&#xD;
          2. Any report of wrist/hand, elbow, or shoulder pain in the last 3 months&#xD;
&#xD;
          3. Any chronic medical conditions that may affect pain perception (e.g., diabetes, high&#xD;
             blood pressure), kidney dysfunction, muscle damage, or major psychiatric disorder&#xD;
&#xD;
          4. Use of any intervention (including but not limited to medication, massage, and&#xD;
             stretching) for symptoms induced by pain training for the duration of the study&#xD;
&#xD;
          5. Positive result on pre-MRI metal screening or pregnancy test due to contraindication&#xD;
             for the MRI environment.&#xD;
&#xD;
          6. Any participant with ferromagnetic metal in the head, neck, or abdominal cavity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael E Robinson, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mark D Bishop, PhD</last_name>
    <phone>352-2736112</phone>
    <email>bish@ufl.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jeff Boissoneault, PhD</last_name>
    <phone>352-2736147</phone>
    <email>jboissoneault@phhp.ufl.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Unversity of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 2020</study_first_posted>
  <last_update_submitted>May 1, 2023</last_update_submitted>
  <last_update_submitted_qc>May 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 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>Musculoskeletal Pain</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/NCT04441619
org study id: IRB20190295 3-N
secondary id: R01AR073745-01A1
nct id: NCT04441619
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This project proposes to understand the sources of pain variability, and demonstrate that
      pain variability represents fluctuation in natural pain management. The project further
      proposes to determine if endogenous capacity to modulate pain can be trained to maximize
      their body's ability to manage pain, much as the way in which athletic performance can be
      trained.
Many physiological systems (bioenergy, immune etc.) involve feedback mechanisms to respond to
      challenges, with increased output or capacity for adaptive change. A similar process is
      plausible for pain modulation where previous successful pain experience and resolution
      suggests a pain modulatory system with adaptive capacity. The proposed research examines how
      a musculoskeletal training program modulates pain response in people with fibromyalgia
      compared to healthy individuals. Previous research suggests that moderate-high level exercise
      is associated with attenuation of pain sensitivity and clinical pain intensity in healthy
      individuals. The proposal seeks to extend findings from previous research and examine how
      repeated exposure and subsequent adaptations to musculoskeletal pain over time influence pain
      modulation (PMC). The first outcome is that people with fibromyalgia (FM) will have PMC
      trainability similar to asymptomatic controls, with the obvious implications for clinical
      application. The second outcome is that FM patients will demonstrate a deficit in PMC
      trainability. This outcome will represent an important diagnostic sign, and guide research to
      additional mechanistic investigation. The third outcome is that impaired or lessened PMC
      trainability is evident in FM patients and this variability can be explored as an individual
      difference with clinical implications. The theoretical fourth potential outcome is
      sensitization in FM patients, however pilot data show that DOMS resolves within the same
      relative time window as controls. Though not hypothesized, the data and design will allow for
      examination of this possibility. One potential conclusion from these projects could be that
      FM arises from an inability to enter a recovery period within which PMC could adapt and
      increase resilience. The proposal will be able to address at least some of the potential for
      this inability to recover.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a mechanistic observational study
primary purpose: Other
masking: Single (Outcomes Assessor)
masking description: Assessments will be performed by an investigator who is not aware of the group assignment.
measure: Change in pain intensity
time frame: Baseline up to 10 weeks
description: Pain during movement and pain at rest using the visual analog scale (VAS). Scores are recorded every day by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain.
measure: Change in thermal quantitative sensory testing
time frame: Baseline up to 10 weeks
description: Thermal pain thresholds and suprathreshold responses will be collected using a numeric rating scale anchored 0 "no pain" and 10 "worst pain imaginable". Change will be calculated using simple change scores and more complex multi-level modeling.
measure: Change in pressure quantitative sensory testing
time frame: Baseline up to 10 weeks
description: Pressure pain threshold will be collected using a numeric rating scale anchored 0 "no pain" and 10 "worst pain imaginable". Change will be calculated using simple change scores and more complex multi-level modeling.
measure: Cortical network connectivity
time frame: Baseline up to 10 weeks
description: Functional magnetic resonance imaging of regional connectivity among pain-related brain regions
arm group label: Repeated exposure
arm group type: Active Comparator
description: Participants will complete four exercise sessions designed to induce delayed onset muscle soreness in the biceps
arm group label: Single exposure
arm group type: Active Comparator
description: Participants will complete one exercise session designed to induce delayed onset muscle soreness
arm group label: Natural history
arm group type: No Intervention
description: Participants will complete all sensory testing and imaging but not perform any exercise sessions.
intervention type: Behavioral
intervention name: Delayed onset muscle soreness.
description: Participants will perform a fatiguing exercise protocol for the upper extremity (biceps muscles)
arm group label: Repeated exposure
arm group label: Single exposure
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Michael E Robinson, PhD
role: Principal Investigator
affiliation: University of Florida
last name: Mark D Bishop, PhD
phone: 352-2736112
email: bish@ufl.edu
last name: Jeff Boissoneault, PhD
phone: 352-2736147
email: jboissoneault@phhp.ufl.edu
facility: 
status: Recruiting
country: United States
responsible party type: Sponsor
mesh term: Musculoskeletal Pain