<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/NCT02261688</url>
  </required_header>
  <id_info>
    <org_study_id>2013P002358</org_study_id>
    <nct_id>NCT02261688</nct_id>
  </id_info>
  <brief_title>Salt and TH-17 in Healthy Human Subjects</brief_title>
  <official_title>Evaluation of the Influence of Salt Intake on TH17 Interleukin(IL)-17 Producing CD4+ Helper T Cells in Human Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall goal of this study is to evaluate the association between sodium and TH17 cells&#xD;
      in human subjects. The subjects will have levels of TH-17 and various hormones measured on&#xD;
      low salt diet, low salt diet with intravenous normal saline, and high salt diet.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In recent years, dietary sodium intake has dramatically increased and has been shown to play&#xD;
      an active role in a number of detrimental diseases including hypertension and cardiovascular&#xD;
      complications. Additionally, in the developed world, there has been a steady increase in&#xD;
      autoimmune diseases. Type 17 helper T cells (Th17) have been shown to play an active role in&#xD;
      the development of autoimmune diseases.&#xD;
&#xD;
      Serum glucocorticoid kinase (SGK1) has been shown to influence sodium transport and salt&#xD;
      homeostasis in many cell types (Wulf, J. Clin. Invest. 2002; Salker, Nature Med 2011). Prior&#xD;
      in vitro and in vivo studies have shown that an increase in salt concentration in the media&#xD;
      or dietary salt intake in mice induces SGK1 expression and enhances TH17 cell differentiation&#xD;
      and worsens experimental autoimmune encephalomyelitis (EAE), animal model for multiple&#xD;
      sclerosis (Kleinewietfeld, Nature 2013; Wu, Nature 2013).&#xD;
&#xD;
      The findings in this study can substantially increase the investigators understanding of&#xD;
      environmental factors that modulate the development of autoimmunity in humans. In animal&#xD;
      models the worsening effects of a high salt diet on EAE are dramatic. To the investigators&#xD;
      knowledge, the proposed study will be the first to determine if salt intake has the same&#xD;
      adverse impact in humans. If documented, one could envision the development of a novel&#xD;
      treatment approach for human autoimmunity via the regulation of salt intake. Thus, the&#xD;
      overall goal of this study is to evaluate the association between sodium and TH17 cells in&#xD;
      human subjects. In addition to measuring TH17 cells by flow cytometry the investigators will&#xD;
      also measure interleukins such as IL-17a, IL-17f, IL-23 that are important in TH17&#xD;
      differentiation and production.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of funds&#xD;
  </why_stopped>
  <start_date type="Actual">March 2014</start_date>
  <completion_date type="Actual">August 2019</completion_date>
  <primary_completion_date type="Actual">July 2019</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>TH-17 levels</measure>
    <time_frame>5 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>IL-17 levels</measure>
    <time_frame>5 days</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Th17 Helper Immune Cells</condition>
  <condition>Autoimmunity</condition>
  <condition>Salt Intake</condition>
  <condition>Sodium Chloride</condition>
  <arm_group>
    <arm_group_label>Subjects in study</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All subjects in study are in a cross-over study with 3 interventions sequentially (low salt diet, low salt diet + IV normal saline, liberal salt diet)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Low salt diet</intervention_name>
    <description>Low salt diet, 10mmoL of sodium per day, for 6 days</description>
    <arm_group_label>Subjects in study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Low salt diet + IV normal saline</intervention_name>
    <description>Low salt diet, 10 mmoL of sodium per day, for 4 days with normal saline infusion x 12 hours per day for 200 mmoL of sodium chloride. Total daily sodium is 210 mmoL/day.</description>
    <arm_group_label>Subjects in study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Liberal salt diet</intervention_name>
    <description>Liberal salt diet targeting 200 mmoL of sodium per day x 7 days</description>
    <arm_group_label>Subjects in study</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  We will seek normal, healthy volunteers age 18-45 years. Participants must be healthy,&#xD;
             BMI 18-25.&#xD;
&#xD;
          -  We will first recruit male subjects into the pilot study to fully assess the&#xD;
             relationship between immune status and salt intake in the absence of hormonal&#xD;
             influences (ovulation and menstruation) to establish a baseline understanding before&#xD;
             embarking on such a study in women. We will study healthy women subjects in a&#xD;
             subsequent later study.&#xD;
&#xD;
        Subjects must have normal laboratory values for:&#xD;
&#xD;
          1. Complete blood count&#xD;
&#xD;
          2. Serum creatinine, sodium, potassium, glucose, liver enzymes&#xD;
&#xD;
          3. Urinalysis&#xD;
&#xD;
          4. Normal ECG&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        We will exclude individuals with:&#xD;
&#xD;
          -  Systolic blood pressure &gt; 140 or &lt; 90&#xD;
&#xD;
          -  Diastolic blood pressure &gt;90 or &lt; 60&#xD;
&#xD;
          -  Creatinine Clearance is abnormal (MDRD formula)&#xD;
&#xD;
          -  Known DM, CHF, CAD, PVD, CVA, MI, or RAS.&#xD;
&#xD;
          -  Known autoimmune disease (including thyroid disease, asthma, inflammatory bowel&#xD;
             disease, rheumatologic diseases)&#xD;
&#xD;
          -  Known neurologic disease (i.e. MS)&#xD;
&#xD;
          -  Steroid use (oral or inhaled, chronic or within the past 6 months)&#xD;
&#xD;
          -  Significant concomitant medical illnesses (cancer, chronic active immunological&#xD;
             conditions, etc.)&#xD;
&#xD;
          -  If spot Na &gt; 30 after low salt diet&#xD;
&#xD;
          -  Current excessive etoh (&gt;10oz/etoh/week)&#xD;
&#xD;
          -  Current use of recreational drugs&#xD;
&#xD;
          -  Current smokers&#xD;
&#xD;
          -  Abnormal labs&#xD;
&#xD;
          -  Acute hospitalizations including surgery in the past 6 months&#xD;
&#xD;
          -  Chronic use of non-steroidal anti-inflammatory or narcotic medications&#xD;
&#xD;
          -  Evidence of ischemia or heart block on screening electrocardiogram (greater than type&#xD;
             I-second degree heart block, left bundle branch block, or&#xD;
&#xD;
          -  ST-T wave changes in 2 or more contiguous leads)&#xD;
&#xD;
          -  Subjects taking any prescription medications (with the exception of birth control&#xD;
             pills) or herbal medications will be excluded).&#xD;
&#xD;
          -  Ingestion of probiotics within last 3 months&#xD;
&#xD;
          -  Antibiotic use within last 3 months&#xD;
&#xD;
          -  1st degree relative with an onset of diabetes or hypertension before the age of 60&#xD;
&#xD;
          -  1st degree relative with autoimmune disease (including thyroid disease, asthma,&#xD;
             inflammatory bowel disease, rheumatologic diseases)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gordon Williams, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>October 7, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <last_update_submitted>June 4, 2021</last_update_submitted>
  <last_update_submitted_qc>June 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Gordon H. Williams, MD</investigator_full_name>
    <investigator_title>Chief, Cardiovascular Endocrinology Section, Brigham and Women's Hospital</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autoimmune Diseases</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/NCT02261688
org study id: 2013P002358
nct id: NCT02261688
lead sponsor: 
has dmc: Yes
The overall goal of this study is to evaluate the association between sodium and TH17 cells
      in human subjects. The subjects will have levels of TH-17 and various hormones measured on
      low salt diet, low salt diet with intravenous normal saline, and high salt diet.
In recent years, dietary sodium intake has dramatically increased and has been shown to play
      an active role in a number of detrimental diseases including hypertension and cardiovascular
      complications. Additionally, in the developed world, there has been a steady increase in
      autoimmune diseases. Type 17 helper T cells (Th17) have been shown to play an active role in
      the development of autoimmune diseases.

      Serum glucocorticoid kinase (SGK1) has been shown to influence sodium transport and salt
      homeostasis in many cell types (Wulf, J. Clin. Invest. 2002; Salker, Nature Med 2011). Prior
      in vitro and in vivo studies have shown that an increase in salt concentration in the media
      or dietary salt intake in mice induces SGK1 expression and enhances TH17 cell differentiation
      and worsens experimental autoimmune encephalomyelitis (EAE), animal model for multiple
      sclerosis (Kleinewietfeld, Nature 2013; Wu, Nature 2013).

      The findings in this study can substantially increase the investigators understanding of
      environmental factors that modulate the development of autoimmunity in humans. In animal
      models the worsening effects of a high salt diet on EAE are dramatic. To the investigators
      knowledge, the proposed study will be the first to determine if salt intake has the same
      adverse impact in humans. If documented, one could envision the development of a novel
      treatment approach for human autoimmunity via the regulation of salt intake. Thus, the
      overall goal of this study is to evaluate the association between sodium and TH17 cells in
      human subjects. In addition to measuring TH17 cells by flow cytometry the investigators will
      also measure interleukins such as IL-17a, IL-17f, IL-23 that are important in TH17
      differentiation and production.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: TH-17 levels
time frame: 5 days
measure: IL-17 levels
time frame: 5 days
arm group label: Subjects in study
arm group type: Other
description: All subjects in study are in a cross-over study with 3 interventions sequentially (low salt diet, low salt diet + IV normal saline, liberal salt diet)
intervention type: Dietary Supplement
intervention name: Low salt diet
description: Low salt diet, 10mmoL of sodium per day, for 6 days
arm group label: Subjects in study
intervention type: Dietary Supplement
intervention name: Low salt diet + IV normal saline
description: Low salt diet, 10 mmoL of sodium per day, for 4 days with normal saline infusion x 12 hours per day for 200 mmoL of sodium chloride. Total daily sodium is 210 mmoL/day.
arm group label: Subjects in study
intervention type: Dietary Supplement
intervention name: Liberal salt diet
description: Liberal salt diet targeting 200 mmoL of sodium per day x 7 days
arm group label: Subjects in study
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Gordon Williams, MD
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Gordon H. Williams, MD
investigator title: Chief, Cardiovascular Endocrinology Section, Brigham and Women's Hospital
mesh term: Autoimmune Diseases