<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/NCT03263975</url>
  </required_header>
  <id_info>
    <org_study_id>14-03H</org_study_id>
    <nct_id>NCT03263975</nct_id>
  </id_info>
  <brief_title>Effects of Dehydration on Neuromuscular Performance and Sympathetic Control of Cardiovascular Function</brief_title>
  <official_title>Effects of Dehydration on Neuromuscular Performance and Sympathetic Control of Cardiovascular Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>United States Army Research Institute of Environmental Medicine</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>United States Army Research Institute of Environmental Medicine</source>
  <oversight_info>
    <has_dmc>No</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>
      The mechanism(s) by which dehydration (both intra- and extracellular) impairs performance are&#xD;
      still poorly described. A loss of volume results in increased occurrence of orthostatic&#xD;
      intolerance, including dizziness, fatigue, headaches and related symptoms with upright&#xD;
      posture. Any of these symptoms can contribute to decreased performance in maneuvers performed&#xD;
      in the upright posture, which includes many military tasks. Thus, loss of volume challenges&#xD;
      the cardiovascular and blood pressure responses to systemic whole body endurance exercise,&#xD;
      while osmolality is the stimulus for intracellular dehydration that may impair local muscle&#xD;
      force production by impairing contractile function, neural signaling, or both. In this study,&#xD;
      we will compare how both types of dehydration affect MSNA and CAC.&#xD;
&#xD;
      The results of this study will provide mechanistic insight for how dehydration (intra- or&#xD;
      extracellular) impairs systemic whole body and local small muscle performance in vivo. This&#xD;
      Basic Science study seeks to understand how volume and osmolality impact MSNA and CAC as a&#xD;
      basis for improving potential countermeasures, such as a more optimally formulated&#xD;
      rehydration beverage. Therefore, this study directly complements Task Area T10 (Hot Weather&#xD;
      Operations and Hydration: Injury and Performance Optimization) and impacts virtually all 14&#xD;
      Military Operational Medicine Research Program Drivers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Objectives and Hypotheses&#xD;
&#xD;
      Primary Objective&#xD;
&#xD;
      The primary objectives of this study are to understand the in vivo effects of dehydration on:&#xD;
&#xD;
        1. Sympathetic neural control of cardiovascular function (MSNA), and&#xD;
&#xD;
        2. Neuromuscular function (CAC) via the IT Test&#xD;
&#xD;
      The primary hypotheses of this study are:&#xD;
&#xD;
        1. Baseline MSNA, and MSNA responses to tilt, will be higher in response to extracellular&#xD;
           dehydration due to larger intravascular volume losses and greater baroreceptor&#xD;
           unloading.&#xD;
&#xD;
        2. Neuromuscular function (CAC) via the IT Test will a) be more impaired by intracellular&#xD;
           dehydration (cell stress) and b) CAC will show a greater performance reduction than CAR&#xD;
           because it reduces the emphasis placed on the voluntary portion of performance (i.e.,&#xD;
           MVC).&#xD;
&#xD;
      Ancillary Questions/Sub Studies&#xD;
&#xD;
        1. The collection of blood and urine before and after exercise-heat stress and dehydration&#xD;
           provides an opportunity to measure and characterize cytokine and intestinal barrier&#xD;
           integrity marker (I-FAB, claudin-3) responses (blood) and renal stress biomarkers&#xD;
           (urine) in humans. This descriptive research 'sub-study' directly complements Task Area&#xD;
           T10 (Hot Weather Operations and Hydration: Injury and Performance Optimization) near and&#xD;
           mid-term research goals of identifying biomarkers of heat stress for protection against&#xD;
           heat injury. There are no hypotheses associated with this sub-study.&#xD;
&#xD;
        2. The study of dehydration requires rehydration for recovery. Rehydration provides an&#xD;
           opportunity for a novel comparison of renal water retention (urine volume) when&#xD;
           consuming equal volumes of two different commercial beverages (Gatorade® or&#xD;
           Enterade-S®). Unlike Gatorade®, which is a carbohydrate-based beverage containing&#xD;
           electrolytes, Enterade-S® is an amino acid-based beverage containing electrolytes. We&#xD;
           hypothesize that the unique formulation of Enterade-S® will improve the rate of fluid&#xD;
           absorption and fluid retention compared to Gatorade® in both intracellular and&#xD;
           extracellular dehydration trials.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 31, 2014</start_date>
  <completion_date type="Actual">December 1, 2017</completion_date>
  <primary_completion_date type="Actual">December 8, 2016</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>Between groups design</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Water and electrolyte retention</measure>
    <time_frame>180 minutes</time_frame>
    <description>Mass balance measures of total body water and electrolytes</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Body water compartment changes</measure>
    <time_frame>180 minutes</time_frame>
    <description>Osmometric measurements and calculations of body fluid spaces</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Dehydration Hypertonic</condition>
  <condition>Isotonic Dehydration</condition>
  <arm_group>
    <arm_group_label>Exercise heat STress (EHS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EHS - dehydration produced by sweating and fluid restriction; primary loss of body water accompanied by small loss of electrolytes (hypertonicity). Interventions include rehydration with Gatorade or Enterade oral rehydration therapies.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lasix (LAS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>LAS - dehydration produced by Lasix (diuretic, 80 mg oral dose) administration to produce losses of body water accompanied by large losses of electrolytes (isotoncity). Interventions include rehydration with Gatorade or Enterade oral rehydration therapies.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Gatorade or Enterade</intervention_name>
    <description>Commercially available oral rehydration therapies</description>
    <arm_group_label>Exercise heat STress (EHS)</arm_group_label>
    <arm_group_label>Lasix (LAS)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, age 18-45&#xD;
&#xD;
          -  In good health as determined by OMSO General Medical Clearance&#xD;
&#xD;
          -  Passed his/her most recent Army Physical Fitness Test (APFT) (military volunteers&#xD;
             only) or exercise at least 2 times per week (civilian volunteers)&#xD;
&#xD;
          -  Ability to comprehend and willingness to sign informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Females who are pregnant or planning to become pregnant during the study&#xD;
&#xD;
          -  Taking prescription or over the counter medication, other than a contraceptive (unless&#xD;
             approved by OMSO and PI)&#xD;
&#xD;
          -  Physical problems/injuries associated with walking or cycling&#xD;
&#xD;
          -  Allergy to sulfa drugs (Lasix™ or sulfonamide antibiotics such as Septra™)&#xD;
&#xD;
          -  Allergy to skin adhesive&#xD;
&#xD;
          -  Hemoglobinopathy (sickle cell trait)&#xD;
&#xD;
          -  Heart, lung, kidney, muscle, or nerve disorder(s)&#xD;
&#xD;
          -  History of heat or orthostatic intolerance&#xD;
&#xD;
          -  Diagnosed and/or treated for fluid/electrolyte imbalance within the last 30 days&#xD;
&#xD;
          -  Presence of metal implants/electronic medical devices in lower extremities&#xD;
&#xD;
          -  Current or previous (within the past 5 years) diagnosis of any autonomic disorder,&#xD;
             including idiopathic orthostatic intolerance, orthostatic hypotension, postural&#xD;
             tachycardia syndrome (POTS), or neurocardiogenic syncope (MSNA group only)&#xD;
&#xD;
          -  Tobacco/nicotine use (MSNA group only)&#xD;
&#xD;
          -  Significant muscle, joint, or bone injury affecting the legs within the last 6 months&#xD;
             (CAC group only)&#xD;
&#xD;
          -  Difficulty swallowing large pills&#xD;
&#xD;
          -  History of obstructive disease of the gastrointestinal tract including (but not&#xD;
             limited to) diverticulosis, diverticulitis and inflammatory bowel disease, peptic&#xD;
             ulcer disease, Crohn's disease, ulcerative colitis; or previous gastrointestinal&#xD;
             surgery.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>April 20, 2020</last_update_submitted>
  <last_update_submitted_qc>April 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 22, 2020</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>Dehydration</mesh_term>
  </condition_browse>
  <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/NCT03263975
org study id: 14-03H
nct id: NCT03263975
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The mechanism(s) by which dehydration (both intra- and extracellular) impairs performance are
      still poorly described. A loss of volume results in increased occurrence of orthostatic
      intolerance, including dizziness, fatigue, headaches and related symptoms with upright
      posture. Any of these symptoms can contribute to decreased performance in maneuvers performed
      in the upright posture, which includes many military tasks. Thus, loss of volume challenges
      the cardiovascular and blood pressure responses to systemic whole body endurance exercise,
      while osmolality is the stimulus for intracellular dehydration that may impair local muscle
      force production by impairing contractile function, neural signaling, or both. In this study,
      we will compare how both types of dehydration affect MSNA and CAC.

      The results of this study will provide mechanistic insight for how dehydration (intra- or
      extracellular) impairs systemic whole body and local small muscle performance in vivo. This
      Basic Science study seeks to understand how volume and osmolality impact MSNA and CAC as a
      basis for improving potential countermeasures, such as a more optimally formulated
      rehydration beverage. Therefore, this study directly complements Task Area T10 (Hot Weather
      Operations and Hydration: Injury and Performance Optimization) and impacts virtually all 14
      Military Operational Medicine Research Program Drivers.
Study Objectives and Hypotheses

      Primary Objective

      The primary objectives of this study are to understand the in vivo effects of dehydration on:

        1. Sympathetic neural control of cardiovascular function (MSNA), and

        2. Neuromuscular function (CAC) via the IT Test

      The primary hypotheses of this study are:

        1. Baseline MSNA, and MSNA responses to tilt, will be higher in response to extracellular
           dehydration due to larger intravascular volume losses and greater baroreceptor
           unloading.

        2. Neuromuscular function (CAC) via the IT Test will a) be more impaired by intracellular
           dehydration (cell stress) and b) CAC will show a greater performance reduction than CAR
           because it reduces the emphasis placed on the voluntary portion of performance (i.e.,
           MVC).

      Ancillary Questions/Sub Studies

        1. The collection of blood and urine before and after exercise-heat stress and dehydration
           provides an opportunity to measure and characterize cytokine and intestinal barrier
           integrity marker (I-FAB, claudin-3) responses (blood) and renal stress biomarkers
           (urine) in humans. This descriptive research 'sub-study' directly complements Task Area
           T10 (Hot Weather Operations and Hydration: Injury and Performance Optimization) near and
           mid-term research goals of identifying biomarkers of heat stress for protection against
           heat injury. There are no hypotheses associated with this sub-study.

        2. The study of dehydration requires rehydration for recovery. Rehydration provides an
           opportunity for a novel comparison of renal water retention (urine volume) when
           consuming equal volumes of two different commercial beverages (Gatorade® or
           Enterade-S®). Unlike Gatorade®, which is a carbohydrate-based beverage containing
           electrolytes, Enterade-S® is an amino acid-based beverage containing electrolytes. We
           hypothesize that the unique formulation of Enterade-S® will improve the rate of fluid
           absorption and fluid retention compared to Gatorade® in both intracellular and
           extracellular dehydration trials.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Between groups design
primary purpose: Treatment
masking: None (Open Label)
measure: Water and electrolyte retention
time frame: 180 minutes
description: Mass balance measures of total body water and electrolytes
measure: Body water compartment changes
time frame: 180 minutes
description: Osmometric measurements and calculations of body fluid spaces
arm group label: Exercise heat STress (EHS)
arm group type: Experimental
description: EHS - dehydration produced by sweating and fluid restriction; primary loss of body water accompanied by small loss of electrolytes (hypertonicity). Interventions include rehydration with Gatorade or Enterade oral rehydration therapies.
arm group label: Lasix (LAS)
arm group type: Experimental
description: LAS - dehydration produced by Lasix (diuretic, 80 mg oral dose) administration to produce losses of body water accompanied by large losses of electrolytes (isotoncity). Interventions include rehydration with Gatorade or Enterade oral rehydration therapies.
intervention type: Other
intervention name: Gatorade or Enterade
description: Commercially available oral rehydration therapies
arm group label: Exercise heat STress (EHS)
arm group label: Lasix (LAS)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Sponsor
mesh term: Dehydration
sharing ipd: No