<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/NCT03768947</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00142795</org_study_id>
    <nct_id>NCT03768947</nct_id>
  </id_info>
  <brief_title>Heat Therapy for Fibromyalgia</brief_title>
  <official_title>Heat Therapy for Fibromyalgia: The Effect on Chronic Pain and Possible Mechanisms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Kansas Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Kansas Medical Center</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to see if heat therapy intervention via hot water immersion&#xD;
      (i.e., a hot tub) is an effective treatment for patients with Fibromyalgia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Fibromyalgia (FM) is a complex and difficult-to-treat painful medical condition and is marked&#xD;
      by chronic widespread musculoskeletal pain, decreased pain threshold, and comorbid&#xD;
      symptomatology (e.g. fatigue, trouble thinking). Several factors appear to play a role in the&#xD;
      pathophysiology of FM: abnormal pain processing, abnormal autonomic nervous and&#xD;
      neuroendocrine system function, genetics, and environmental triggers. The prognosis for&#xD;
      recovery in traditional medicine is generally poor and current pharmacological treatments for&#xD;
      FM are often insufficient to control persistent symptoms. As such, complementary medicine and&#xD;
      alternative lifestyle approaches are needed. Heat therapy, such as saunas and hot tubs, has&#xD;
      been used historically for its presumed therapeutic benefits, and emerging research&#xD;
      highlights the benefits of heat therapy on metabolic and cardiovascular disease risks.&#xD;
      Finnish saunas, which result in total-body heating, have shown beneficial clinical effects&#xD;
      for rheumatic patients and new studies are needed to determine if heat therapy could improve&#xD;
      pain symptoms in patients with FM.&#xD;
&#xD;
      The short-term goal of the investigators is to determine, in a pilot clinical study, that&#xD;
      heat therapy intervention via hot water immersion is a safe and efficacious treatment for&#xD;
      pain in patients with FM. The overall hypothesis is that heat therapy intervention will&#xD;
      improve clinical pain severity and associated dysfunction in a cohort of FM patients and that&#xD;
      the anti-inflammatory actions of heat shock proteins may mediate this improvement. The&#xD;
      proposed interdisciplinary study will provide data regarding treatment efficacy and will&#xD;
      explore potential molecular and physiologic processes that may underlie improvement in pain&#xD;
      symptoms after heat therapy intervention for FM. Furthermore, these key pilot studies will&#xD;
      provide important preliminary data for future studies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 19, 2019</start_date>
  <completion_date type="Actual">March 10, 2020</completion_date>
  <primary_completion_date type="Actual">March 10, 2020</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline Visual Numerical Pain Score (VNS) at 1 month</measure>
    <time_frame>Baseline and 1 Month</time_frame>
    <description>Measured by the Brief Pain Inventory (BPI). The BPI scores are a numerical rating scale and range from 0 to 10. A score of 0 is equal to no pain and a score of 10 is equal to pain as bad as you can imagine.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Patient-Reported Outcomes Measurement Information System (PROMIS) at 1 month</measure>
    <time_frame>Baseline to 1 Month</time_frame>
    <description>PROMIS (Patient-Reported Outcomes Measurement Information System) measures to be included are Depression, Anxiety, Physical Functioning, and Sleep Impairment. Each questionnaire usually has 4-16 response options ranging in value from one to five. The total raw score for a short form with all questions answered is the sum of the values of the response to each question. The total range of potential raw scores depends on the number of questions being asked, for example, a 6 item form would have a range from is 6 to 30. After the raw score is calculated, a T-score metric is used to convert the raw score to a T-score. On the T-score metric, a score of 50 is the mean of a relevant reference population and 10 is the standard deviation of that mean. For PROMIS measures, higher scores equals &quot;more of the concept being measured&quot;, this could be a desirable or undesirable outcome, depending on the concept being measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Revised Fibromyalgia Impact Questionnaire (FIQ-R) at 1 month</measure>
    <time_frame>Baseline and 1 Month</time_frame>
    <description>The Revised Fibromyalgia Impact Questionnaire (FIQ-R) is a measure of symptom severity in fibromyalgia. There is a total of 21 questions and a range of scores from 0 to 210. The higher the score the more severe a person's symptoms.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Quantitative Sensory Testing (QST)-- Pressure pain sensitivity by Multimodal Automated Sensory Testing</measure>
    <time_frame>Baseline and 1 Month</time_frame>
    <description>Pressure pain sensitivity is measured by the Multimodal Automated Sensory Testing (MAST) System (measured at the thumbnail). It yields a pressure pain threshold value measured in kg/cm2.</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood Analyses of Change in Baseline Heat Shock Proteins at 1 month</measure>
    <time_frame>Baseline and 1 Month</time_frame>
    <description>Heat shock proteins including Heat Shock Protein 72 (HSP72), Heat Shock Factor 25 (HSP25), and Heat Shock Factor 1 (HSF1) will be measured via Western blots and Elisa assays in serum at baseline (pre-intervention) and post-intervention (within 48 hours of completion of the one month heat therapy intervention). Each of these specific heat shock proteins is measured as a protein to total protein ratio. For example, HSP25 is measured as HSP25/total protein.</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood Analyses of Change in Pro/Anti-inflammatory Markers at 1 month</measure>
    <time_frame>Baseline and 1 Month</time_frame>
    <description>Pro/Anti-Inflammatory markers (IL-1Ra, IL-1β, IL-6, IL-8, IL-10, IL-18, IFN-α, TNF-α) will be measured via Western blots and Elisa assays in serum at baseline (pre-intervention) and post-intervention (within 48 hours of completion of the protocol). All markers will be measured as concentrations (nanograms/milliliter (ng/mL))</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Fibromyalgia</condition>
  <arm_group>
    <arm_group_label>Heat Therapy Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this open-label pilot study will undergo heat therapy via hot water immersion (hot-tub).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Heat therapy via hot water immersion</intervention_name>
    <description>Participants will be asked to participate in a 4-week heat therapy intervention, which consists of ~12-15 visits (45 min each) of immersion in to a hot tub.</description>
    <arm_group_label>Heat Therapy Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed consent provided by the participant&#xD;
&#xD;
          -  Age 18 to 65 years&#xD;
&#xD;
          -  Diagnosis of FM according to American College of Rheumatology 2011 self-report&#xD;
             criteria64&#xD;
&#xD;
          -  Average BPI visual numerical pain score &gt; 4&#xD;
&#xD;
          -  Stable doses of medications for at least 30 days prior to screening&#xD;
&#xD;
          -  Participant agrees to continue the same medication regimen for the study duration&#xD;
&#xD;
          -  FM patients with a sedentary lifestyle (exercise can alter heat shock protein levels)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to provide informed consent&#xD;
&#xD;
          -  Age greater than 65 years&#xD;
&#xD;
          -  Previous history of hypotension&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Current clinically significant disease that would prevent safe heat therapy/hot water&#xD;
             immersion (heart conditions such as myocardial infarction, angina, uncontrolled&#xD;
             hypertension or kidney disease see below)&#xD;
&#xD;
          -  Reported previous bleeding problems&#xD;
&#xD;
          -  Anti-platelet medication (Plavix), Warfarin, and other anticoagulants (Eliquis,&#xD;
             Pradaxa, and Xarelto)&#xD;
&#xD;
          -  Recent rectal, anal, vaginal or prostate surgery&#xD;
&#xD;
          -  Current litigation for fibromyalgia&#xD;
&#xD;
          -  Current disability proceedings&#xD;
&#xD;
          -  Active psychotic or suicidal symptoms&#xD;
&#xD;
          -  Current drug or alcohol abuse&#xD;
&#xD;
          -  Current regular exercise&#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>Andrea L Nicol, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kansas School of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Paige Geiger, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kansas School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Hauser W, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol. 2011 Jun;38(6):1113-22. doi: 10.3899/jrheum.100594. Epub 2011 Feb 1.</citation>
    <PMID>21285161</PMID>
  </reference>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>November 8, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>June 14, 2022</last_update_submitted>
  <last_update_submitted_qc>June 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Kansas Medical Center</investigator_affiliation>
    <investigator_full_name>Andrea Chadwick, MD, MSc, FASA</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Chronic Pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibromyalgia</mesh_term>
    <mesh_term>Myofascial Pain Syndromes</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03768947
org study id: STUDY00142795
nct id: NCT03768947
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to see if heat therapy intervention via hot water immersion
      (i.e., a hot tub) is an effective treatment for patients with Fibromyalgia.
Fibromyalgia (FM) is a complex and difficult-to-treat painful medical condition and is marked
      by chronic widespread musculoskeletal pain, decreased pain threshold, and comorbid
      symptomatology (e.g. fatigue, trouble thinking). Several factors appear to play a role in the
      pathophysiology of FM: abnormal pain processing, abnormal autonomic nervous and
      neuroendocrine system function, genetics, and environmental triggers. The prognosis for
      recovery in traditional medicine is generally poor and current pharmacological treatments for
      FM are often insufficient to control persistent symptoms. As such, complementary medicine and
      alternative lifestyle approaches are needed. Heat therapy, such as saunas and hot tubs, has
      been used historically for its presumed therapeutic benefits, and emerging research
      highlights the benefits of heat therapy on metabolic and cardiovascular disease risks.
      Finnish saunas, which result in total-body heating, have shown beneficial clinical effects
      for rheumatic patients and new studies are needed to determine if heat therapy could improve
      pain symptoms in patients with FM.

      The short-term goal of the investigators is to determine, in a pilot clinical study, that
      heat therapy intervention via hot water immersion is a safe and efficacious treatment for
      pain in patients with FM. The overall hypothesis is that heat therapy intervention will
      improve clinical pain severity and associated dysfunction in a cohort of FM patients and that
      the anti-inflammatory actions of heat shock proteins may mediate this improvement. The
      proposed interdisciplinary study will provide data regarding treatment efficacy and will
      explore potential molecular and physiologic processes that may underlie improvement in pain
      symptoms after heat therapy intervention for FM. Furthermore, these key pilot studies will
      provide important preliminary data for future studies.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from Baseline Visual Numerical Pain Score (VNS) at 1 month
time frame: Baseline and 1 Month
description: Measured by the Brief Pain Inventory (BPI). The BPI scores are a numerical rating scale and range from 0 to 10. A score of 0 is equal to no pain and a score of 10 is equal to pain as bad as you can imagine.
measure: Change from Baseline Patient-Reported Outcomes Measurement Information System (PROMIS) at 1 month
time frame: Baseline to 1 Month
description: PROMIS (Patient-Reported Outcomes Measurement Information System) measures to be included are Depression, Anxiety, Physical Functioning, and Sleep Impairment. Each questionnaire usually has 4-16 response options ranging in value from one to five. The total raw score for a short form with all questions answered is the sum of the values of the response to each question. The total range of potential raw scores depends on the number of questions being asked, for example, a 6 item form would have a range from is 6 to 30. After the raw score is calculated, a T-score metric is used to convert the raw score to a T-score. On the T-score metric, a score of 50 is the mean of a relevant reference population and 10 is the standard deviation of that mean. For PROMIS measures, higher scores equals "more of the concept being measured", this could be a desirable or undesirable outcome, depending on the concept being measured.
measure: Change from Baseline Revised Fibromyalgia Impact Questionnaire (FIQ-R) at 1 month
time frame: Baseline and 1 Month
description: The Revised Fibromyalgia Impact Questionnaire (FIQ-R) is a measure of symptom severity in fibromyalgia. There is a total of 21 questions and a range of scores from 0 to 210. The higher the score the more severe a person's symptoms.
measure: Quantitative Sensory Testing (QST)-- Pressure pain sensitivity by Multimodal Automated Sensory Testing
time frame: Baseline and 1 Month
description: Pressure pain sensitivity is measured by the Multimodal Automated Sensory Testing (MAST) System (measured at the thumbnail). It yields a pressure pain threshold value measured in kg/cm2.
measure: Blood Analyses of Change in Baseline Heat Shock Proteins at 1 month
time frame: Baseline and 1 Month
description: Heat shock proteins including Heat Shock Protein 72 (HSP72), Heat Shock Factor 25 (HSP25), and Heat Shock Factor 1 (HSF1) will be measured via Western blots and Elisa assays in serum at baseline (pre-intervention) and post-intervention (within 48 hours of completion of the one month heat therapy intervention). Each of these specific heat shock proteins is measured as a protein to total protein ratio. For example, HSP25 is measured as HSP25/total protein.
measure: Blood Analyses of Change in Pro/Anti-inflammatory Markers at 1 month
time frame: Baseline and 1 Month
description: Pro/Anti-Inflammatory markers (IL-1Ra, IL-1β, IL-6, IL-8, IL-10, IL-18, IFN-α, TNF-α) will be measured via Western blots and Elisa assays in serum at baseline (pre-intervention) and post-intervention (within 48 hours of completion of the protocol). All markers will be measured as concentrations (nanograms/milliliter (ng/mL))
arm group label: Heat Therapy Arm
arm group type: Experimental
description: Participants in this open-label pilot study will undergo heat therapy via hot water immersion (hot-tub).
intervention type: Other
intervention name: Heat therapy via hot water immersion
description: Participants will be asked to participate in a 4-week heat therapy intervention, which consists of ~12-15 visits (45 min each) of immersion in to a hot tub.
arm group label: Heat Therapy Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Andrea L Nicol, MD
role: Principal Investigator
affiliation: University of Kansas School of Medicine
last name: Paige Geiger, PhD
role: Principal Investigator
affiliation: University of Kansas School of Medicine
facility: 
country: United States
citation: Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Hauser W, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol. 2011 Jun;38(6):1113-22. doi: 10.3899/jrheum.100594. Epub 2011 Feb 1.
PMID: 21285161
responsible party type: Principal Investigator
investigator affiliation: University of Kansas Medical Center
investigator full name: Andrea Chadwick, MD, MSc, FASA
investigator title: Assistant Professor
mesh term: Fibromyalgia
mesh term: Myofascial Pain Syndromes
sharing ipd: Undecided