<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/NCT03264508</url>
  </required_header>
  <id_info>
    <org_study_id>16-0757</org_study_id>
    <nct_id>NCT03264508</nct_id>
  </id_info>
  <brief_title>Passive Heat Therapy and Age-associated Physiological Function</brief_title>
  <official_title>Passive Heat Therapy and Age-associated Physiological Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Douglas Seals</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Boulder</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 study aims to determine the effects of 8-10 weeks of repeated hot water immersion (&quot;heat&#xD;
      therapy&quot;) vs. thermoneutral water immersion on vascular function in late middle-aged to older&#xD;
      (55-79 years) adults.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Advancing age is the primary risk factor for cardiovascular diseases (CVD), which remain the&#xD;
      leading cause of death in the developed world. The key process that links aging to increased&#xD;
      risk of CVD is the development of arterial dysfunction, including impaired endothelial&#xD;
      function and arterial stiffening. In addition, age-associated impairments in arterial&#xD;
      function have been linked to other diseases/disorders of aging, including cognitive&#xD;
      impairments, Alzheimer's disease and dementia, and motor disorders/disability.&#xD;
&#xD;
      Passive heat therapy, in the form of repeated use of hot baths and saunas, has been used by&#xD;
      several cultures for centuries; however, the physiological benefits are only now being&#xD;
      elucidated. For example, recent studies have found that lifelong habitual sauna use is&#xD;
      associated with considerably reduced risk of all-cause mortality, sudden cardiac death,&#xD;
      CVD-related death, and Alzheimer's disease and dementia. In addition, 8-10 weeks of hot water&#xD;
      immersion in young adults has been shown to improve endothelial function and reduces arterial&#xD;
      stiffness and blood pressure. Therefore, the investigators expect heat therapy to similarly&#xD;
      improve vascular function, as well as cognitive and motor function, in middle-aged to older&#xD;
      adults who are at greater risk of CVD and related diseases/disorders.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 25, 2017</start_date>
  <completion_date type="Actual">June 1, 2021</completion_date>
  <primary_completion_date type="Actual">November 23, 2020</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>Randomized, controlled (parallel design), single-blind</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Investigator)</masking>
    <masking_description>Investigators collecting and analyzing data will be blinded to subject treatment arms. It is not possible to blind subjects.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Brachial artery flow-mediated dilation</measure>
    <time_frame>0 and 8 weeks</time_frame>
    <description>Measure of endothelial function</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Carotid-femoral pulse wave velocity</measure>
    <time_frame>0 and 8 weeks</time_frame>
    <description>Measure of central arterial stiffness</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean arterial blood pressure</measure>
    <time_frame>0 and 8 weeks</time_frame>
    <description>Brachial artery blood pressure, measured in triplicate (and averaged) following 20 min of supine rest</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cerebrovascular reactivity</measure>
    <time_frame>0 and 8 weeks</time_frame>
    <description>Measure of cerebral vascular function; magnitude of increase in blood flow through the middle cerebral artery in response to breathing 5% CO2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fluid cognition composite score</measure>
    <time_frame>0 and 8 weeks</time_frame>
    <description>Multiple domains of cognitive function (incl. executive function, memory, processing speed) assessed using the NIH toolbox (aggregated into one reported value)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Motor function composite score</measure>
    <time_frame>0 and 8 weeks</time_frame>
    <description>Multiple domains of motor function (incl. endurance, strength, dexterity) assessed using the NIH toolbox (aggregated into one reported value)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Aging</condition>
  <arm_group>
    <arm_group_label>Heat therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hot water immersion 3-4x per week for 8-10 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Thermoneutral water immersion</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Thermoneutral water immersion 3-4x per week for 8-10 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Heat therapy</intervention_name>
    <description>30 sessions (3-4x per week for 8-10 weeks) of hot water immersion in 40°C water, sufficient to raise body core temperature to 38.5°C.</description>
    <arm_group_label>Heat therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Thermoneutral water immersion</intervention_name>
    <description>30 sessions (3-4x per week for 8-10 weeks) of hot water immersion in 36°C water to prevent changes in body core temperature &gt;0.2°C.</description>
    <arm_group_label>Thermoneutral water immersion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to provide informed consent.&#xD;
&#xD;
          -  Aged 55-79 years. Women must be postmenopausal and not taking hormone replacement&#xD;
             therapy within the past year.&#xD;
&#xD;
          -  Sedentary to recreationally active: participating in vigorous aerobic exercise &lt;4x/wk&#xD;
             for ≥ 3 yrs.&#xD;
&#xD;
          -  Able to refrain from the use of dietary supplements, anti-inflammatory medications,&#xD;
             and prescription medications for 24-48h prior to experimental testing.&#xD;
&#xD;
          -  Generally healthy (no overt clinical disease), as determined by medical history,&#xD;
             physical examination, blood and urine chemistries.&#xD;
&#xD;
          -  Ankle-brachial blood pressure index &gt;0.7&#xD;
&#xD;
          -  Total cholesterol &lt;240 mg/dl (&lt;6.2 mmol/L)&#xD;
&#xD;
          -  Fasting plasma glucose &lt;126 mg/dl (&lt;7.0 mmol/L)&#xD;
&#xD;
          -  Systolic blood pressure &lt; 160 mmHg and &gt;100 mmHg&#xD;
&#xD;
          -  Glomerular filtration rate &gt; 60 ml/min/1.73 m2&#xD;
&#xD;
          -  Mini mental state exam score &gt; 20 points&#xD;
&#xD;
          -  Body mass index (BMI) &lt;30 kg/m2&#xD;
&#xD;
          -  Weight stable in the prior 3 months (≤ 2 kg weight change) and willing to remain&#xD;
             weight stable over the course of the study&#xD;
&#xD;
          -  Free from alcohol dependence or abuse, as defined by the American Psychiatry&#xD;
             Association, Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current use of certain prescription medications that may interfere with&#xD;
             thermoregulation and/or blood pressure control during heat stress. These include&#xD;
             anti-hypertensives (in particular beta-blockers), nitrates and nitrites (e.g.&#xD;
             nitroglycerin), PDE5 inhibitors (e.g. Viagra), anticholinergics (e.g. amitriptyline),&#xD;
             and alpha-blockers (e.g. Flomax).&#xD;
&#xD;
          -  Orthostatic hypotension&#xD;
&#xD;
          -  Current or past smoking within the last 5 years&#xD;
&#xD;
          -  Recent major change in health status within previous 6 months (i.e. surgery,&#xD;
             significant infection or illness).&#xD;
&#xD;
          -  Chronic clinical diseases (e.g., inflammatory bowel diseases/irritable bowel syndrome,&#xD;
             coronary artery/peripheral artery/cerebrovascular diseases, diabetes, chronic kidney&#xD;
             disease requiring dialysis, neurological disorders or diseases that may affect&#xD;
             motor/cognitive functions [multiple sclerosis, Parkinson's disease, polio, Alzheimer's&#xD;
             disease, dementia or other brain diseases of aging]).&#xD;
&#xD;
          -  History of heat-related illness&#xD;
&#xD;
          -  Open wounds or skin lesions. History of skin-related conditions or sensitivities to&#xD;
             prolonged water immersion or exposure to pool chemicals.&#xD;
&#xD;
          -  Blood donation within the past 2 months&#xD;
&#xD;
          -  Inability to tolerate blood draws, intravenous catheters, and/or fingertip blood&#xD;
             sampling, including past fainting in response to blood sampling.&#xD;
&#xD;
          -  Rectal, anal, vaginal, or prostate surgery within the last 6 months, current or recent&#xD;
             (within the last 6 months) hemorrhoids, or related concerns regarding use of rectal&#xD;
             thermistor&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Douglas R Seals, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Boulder</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado Boulder</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Brunt VE, Howard MJ, Francisco MA, Ely BR, Minson CT. Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans. J Physiol. 2016 Sep 15;594(18):5329-42. doi: 10.1113/JP272453. Epub 2016 Jun 30.</citation>
    <PMID>27270841</PMID>
  </reference>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>October 27, 2021</last_update_submitted>
  <last_update_submitted_qc>October 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Colorado, Boulder</investigator_affiliation>
    <investigator_full_name>Douglas Seals</investigator_full_name>
    <investigator_title>Professor of Distinction</investigator_title>
  </responsible_party>
  <keyword>endothelial function</keyword>
  <keyword>arterial stiffness</keyword>
  <keyword>heat</keyword>
  <keyword>hot water immersion</keyword>
  <patient_data>
    <sharing_ipd>No</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/NCT03264508
org study id: 16-0757
nct id: NCT03264508
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study aims to determine the effects of 8-10 weeks of repeated hot water immersion ("heat
      therapy") vs. thermoneutral water immersion on vascular function in late middle-aged to older
      (55-79 years) adults.
Advancing age is the primary risk factor for cardiovascular diseases (CVD), which remain the
      leading cause of death in the developed world. The key process that links aging to increased
      risk of CVD is the development of arterial dysfunction, including impaired endothelial
      function and arterial stiffening. In addition, age-associated impairments in arterial
      function have been linked to other diseases/disorders of aging, including cognitive
      impairments, Alzheimer's disease and dementia, and motor disorders/disability.

      Passive heat therapy, in the form of repeated use of hot baths and saunas, has been used by
      several cultures for centuries; however, the physiological benefits are only now being
      elucidated. For example, recent studies have found that lifelong habitual sauna use is
      associated with considerably reduced risk of all-cause mortality, sudden cardiac death,
      CVD-related death, and Alzheimer's disease and dementia. In addition, 8-10 weeks of hot water
      immersion in young adults has been shown to improve endothelial function and reduces arterial
      stiffness and blood pressure. Therefore, the investigators expect heat therapy to similarly
      improve vascular function, as well as cognitive and motor function, in middle-aged to older
      adults who are at greater risk of CVD and related diseases/disorders.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, controlled (parallel design), single-blind
primary purpose: Basic Science
masking: Single (Investigator)
masking description: Investigators collecting and analyzing data will be blinded to subject treatment arms. It is not possible to blind subjects.
measure: Brachial artery flow-mediated dilation
time frame: 0 and 8 weeks
description: Measure of endothelial function
measure: Carotid-femoral pulse wave velocity
time frame: 0 and 8 weeks
description: Measure of central arterial stiffness
measure: Mean arterial blood pressure
time frame: 0 and 8 weeks
description: Brachial artery blood pressure, measured in triplicate (and averaged) following 20 min of supine rest
measure: Cerebrovascular reactivity
time frame: 0 and 8 weeks
description: Measure of cerebral vascular function; magnitude of increase in blood flow through the middle cerebral artery in response to breathing 5% CO2
measure: Fluid cognition composite score
time frame: 0 and 8 weeks
description: Multiple domains of cognitive function (incl. executive function, memory, processing speed) assessed using the NIH toolbox (aggregated into one reported value)
measure: Motor function composite score
time frame: 0 and 8 weeks
description: Multiple domains of motor function (incl. endurance, strength, dexterity) assessed using the NIH toolbox (aggregated into one reported value)
arm group label: Heat therapy
arm group type: Experimental
description: Hot water immersion 3-4x per week for 8-10 weeks
arm group label: Thermoneutral water immersion
arm group type: Sham Comparator
description: Thermoneutral water immersion 3-4x per week for 8-10 weeks
intervention type: Behavioral
intervention name: Heat therapy
description: 30 sessions (3-4x per week for 8-10 weeks) of hot water immersion in 40°C water, sufficient to raise body core temperature to 38.5°C.
arm group label: Heat therapy
intervention type: Behavioral
intervention name: Thermoneutral water immersion
description: 30 sessions (3-4x per week for 8-10 weeks) of hot water immersion in 36°C water to prevent changes in body core temperature >0.2°C.
arm group label: Thermoneutral water immersion
criteria: 
gender: All
minimum age: 55 Years
maximum age: 79 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Douglas R Seals, PhD
role: Principal Investigator
affiliation: University of Colorado, Boulder
facility: 
country: United States
citation: Brunt VE, Howard MJ, Francisco MA, Ely BR, Minson CT. Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans. J Physiol. 2016 Sep 15;594(18):5329-42. doi: 10.1113/JP272453. Epub 2016 Jun 30.
PMID: 27270841
responsible party type: Sponsor-Investigator
investigator affiliation: University of Colorado, Boulder
investigator full name: Douglas Seals
investigator title: Professor of Distinction
sharing ipd: No