<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/NCT03029806</url>
  </required_header>
  <id_info>
    <org_study_id>2015P002540</org_study_id>
    <nct_id>NCT03029806</nct_id>
  </id_info>
  <brief_title>Lysine-specific Demethylase 1 and Salt-sensitivity in Humans</brief_title>
  <official_title>Lysine-specific Demethylase 1 and Salt-sensitivity in Humans</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>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 purpose of this study is to investigate the role dietary salt plays in epigenetic&#xD;
      regulation of blood pressure, focusing on the salt-sensitive regulatory enzyme&#xD;
      Lysine-specific demethylase 1.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to investigate the role dietary salt plays in epigenetic&#xD;
      regulation of blood pressure in African American and Caucasians, focusing on the&#xD;
      salt-sensitive regulatory enzyme Lysine-specific demethylase 1. This might help us understand&#xD;
      why some people develop high blood pressure.&#xD;
&#xD;
      Healthy volunteers will be screened for eligibility and invited to participate in a 2 weeks&#xD;
      study. Week 1 will be consumption of a low salt diet. Week 2 will be a high salt diet.&#xD;
&#xD;
      At the end of each week, participants will be admitted to a Clinical Research Center&#xD;
      overnight and for one day.&#xD;
&#xD;
      On the CRC, participants will remain fasting and supine overnight and then next morning&#xD;
      undergo hormonal and vascular testing. This will consist of blood drawing, echocardiogram,&#xD;
      vascular tonometry, and assessment of renal blood flow before and after a low-dose&#xD;
      Angiotensin II infusion.&#xD;
&#xD;
      The study outcome will compare how variants in the LSD1 gene affect hormonal and vascular&#xD;
      responses according to race. This information will help us determine why some races and&#xD;
      genetic profiles are more susceptible to detrimental effects of salt in the diet while others&#xD;
      are protected against these effects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 2, 2017</start_date>
  <completion_date type="Anticipated">January 2, 2024</completion_date>
  <primary_completion_date type="Actual">January 2, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Heathy volunteers</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Aldosterone response to angiotensin II</measure>
    <time_frame>After 1 week dietary salt manipulation</time_frame>
    <description>Change in aldosterone, baseline to after angiotensin II by genotype/race</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Renal blood flow response to dietary salt</measure>
    <time_frame>After 1 week dietary salt manipulation on both diets</time_frame>
    <description>Change in renal blood flow, high salt diet to low salt diet by genotype/race</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular stiffness response to angiotensin II</measure>
    <time_frame>After 1 week dietary salt manipulation</time_frame>
    <description>Change in vascular stiffness, baseline to after angiotensin II by genotype/race</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">88</enrollment>
  <condition>Healthy Subjects</condition>
  <arm_group>
    <arm_group_label>Afr-Amer risk allele</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>African Americans carrying the LSD1 affected allele</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cauc risk allele</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Caucasians carrying the LSD1 affected allele</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Afr-Amer non-risk allele</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>African Americans carrying the LSD1 non-risk allele</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cauc non-risk allele</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Caucasians carrying the LSD1 non-risk allele</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Aldosterone response to AngII LS</intervention_name>
    <description>Change in aldosterone from baseline to after Ang II infusion on a LS diet</description>
    <arm_group_label>Afr-Amer non-risk allele</arm_group_label>
    <arm_group_label>Afr-Amer risk allele</arm_group_label>
    <arm_group_label>Cauc non-risk allele</arm_group_label>
    <arm_group_label>Cauc risk allele</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Renal blood flow response to salt</intervention_name>
    <description>Change in renal blood flow: High salt to low salt diet</description>
    <arm_group_label>Afr-Amer non-risk allele</arm_group_label>
    <arm_group_label>Afr-Amer risk allele</arm_group_label>
    <arm_group_label>Cauc non-risk allele</arm_group_label>
    <arm_group_label>Cauc risk allele</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Vascular Stiffness</intervention_name>
    <description>Change in vascular stiffness, baseline compared to AngII</description>
    <arm_group_label>Afr-Amer non-risk allele</arm_group_label>
    <arm_group_label>Afr-Amer risk allele</arm_group_label>
    <arm_group_label>Cauc non-risk allele</arm_group_label>
    <arm_group_label>Cauc risk allele</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 25-45 years&#xD;
&#xD;
          -  Caucasian or African American&#xD;
&#xD;
          -  No gender preference (anticipate 50% female)&#xD;
&#xD;
          -  Normotensive (screening blood pressure &lt;140/90 mmHg)&#xD;
&#xD;
          -  No history of hypertension, diabetes, stroke, coronary artery disease, kidney disease,&#xD;
             cancer, thyroid disease, preeclampsia, or hospitalizations in 6 months&#xD;
&#xD;
          -  Normal screening laboratory values (CMP, TSH, A1c)&#xD;
&#xD;
          -  Normal ECG&#xD;
&#xD;
          -  BMI &lt;25 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Breast feeding&#xD;
&#xD;
          -  Any medication or herbal preparation&#xD;
&#xD;
          -  &gt;6oz alcohol/week&#xD;
&#xD;
          -  Tobacco use&#xD;
&#xD;
          -  Illicit drug use&#xD;
&#xD;
          -  Chronic NSAID use&#xD;
&#xD;
          -  Recent steroid use (injected, inhaled, oral)&#xD;
&#xD;
          -  Decongestant use in the past 2 weeks&#xD;
&#xD;
          -  Known sensitivity to infused Angiotensin II or para-amino hippurate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <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>
  <reference>
    <citation>Krug AW, Tille E, Sun B, Pojoga L, Williams J, Chamarthi B, Lichtman AH, Hopkins PN, Adler GK, Williams GH. Lysine-specific demethylase-1 modifies the age effect on blood pressure sensitivity to dietary salt intake. Age (Dordr). 2013 Oct;35(5):1809-20. doi: 10.1007/s11357-012-9480-0. Epub 2012 Oct 2.</citation>
    <PMID>23054827</PMID>
  </reference>
  <reference>
    <citation>Williams JS, Chamarthi B, Goodarzi MO, Pojoga LH, Sun B, Garza AE, Raby BA, Adler GK, Hopkins PN, Brown NJ, Jeunemaitre X, Ferri C, Fang R, Leonor T, Cui J, Guo X, Taylor KD, Ida Chen YD, Xiang A, Raffel LJ, Buchanan TA, Rotter JI, Williams GH, Shi Y. Lysine-specific demethylase 1: an epigenetic regulator of salt-sensitive hypertension. Am J Hypertens. 2012 Jul;25(7):812-7. doi: 10.1038/ajh.2012.43. Epub 2012 Apr 26.</citation>
    <PMID>22534796</PMID>
  </reference>
  <reference>
    <citation>Pojoga LH, Williams JS, Yao TM, Kumar A, Raffetto JD, do Nascimento GR, Reslan OM, Adler GK, Williams GH, Shi Y, Khalil RA. Histone demethylase LSD1 deficiency during high-salt diet is associated with enhanced vascular contraction, altered NO-cGMP relaxation pathway, and hypertension. Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H1862-71. doi: 10.1152/ajpheart.00513.2011. Epub 2011 Aug 26.</citation>
    <PMID>21873498</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <last_update_submitted>February 7, 2023</last_update_submitted>
  <last_update_submitted_qc>February 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 9, 2023</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>Jonathan S. Williams, MD, MMSc</investigator_full_name>
    <investigator_title>Associate Physician, Brigham and Women's Hospital</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD will be shared first thru the publication of research results in peer-review scientific journals by the study investigator. IPD will be made available upon reasonable request from bona fide research organizations in an effort to provide broader impact and enrich public health knowledge. Research volunteer PHI will not be shared, and all participant data will be de-identified and coded. Only encrypted and secure network exchanges will be used for data transfer. Cost sharing my be required in order prepare datasets.</ipd_description>
  </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/NCT03029806
org study id: 2015P002540
nct id: NCT03029806
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to investigate the role dietary salt plays in epigenetic
      regulation of blood pressure, focusing on the salt-sensitive regulatory enzyme
      Lysine-specific demethylase 1.
The purpose of this study is to investigate the role dietary salt plays in epigenetic
      regulation of blood pressure in African American and Caucasians, focusing on the
      salt-sensitive regulatory enzyme Lysine-specific demethylase 1. This might help us understand
      why some people develop high blood pressure.

      Healthy volunteers will be screened for eligibility and invited to participate in a 2 weeks
      study. Week 1 will be consumption of a low salt diet. Week 2 will be a high salt diet.

      At the end of each week, participants will be admitted to a Clinical Research Center
      overnight and for one day.

      On the CRC, participants will remain fasting and supine overnight and then next morning
      undergo hormonal and vascular testing. This will consist of blood drawing, echocardiogram,
      vascular tonometry, and assessment of renal blood flow before and after a low-dose
      Angiotensin II infusion.

      The study outcome will compare how variants in the LSD1 gene affect hormonal and vascular
      responses according to race. This information will help us determine why some races and
      genetic profiles are more susceptible to detrimental effects of salt in the diet while others
      are protected against these effects.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Heathy volunteers
primary purpose: Other
masking: None (Open Label)
measure: Aldosterone response to angiotensin II
time frame: After 1 week dietary salt manipulation
description: Change in aldosterone, baseline to after angiotensin II by genotype/race
measure: Renal blood flow response to dietary salt
time frame: After 1 week dietary salt manipulation on both diets
description: Change in renal blood flow, high salt diet to low salt diet by genotype/race
measure: Vascular stiffness response to angiotensin II
time frame: After 1 week dietary salt manipulation
description: Change in vascular stiffness, baseline to after angiotensin II by genotype/race
arm group label: Afr-Amer risk allele
arm group type: Active Comparator
description: African Americans carrying the LSD1 affected allele
arm group label: Cauc risk allele
arm group type: Placebo Comparator
description: Caucasians carrying the LSD1 affected allele
arm group label: Afr-Amer non-risk allele
arm group type: Placebo Comparator
description: African Americans carrying the LSD1 non-risk allele
arm group label: Cauc non-risk allele
arm group type: Placebo Comparator
description: Caucasians carrying the LSD1 non-risk allele
intervention type: Other
intervention name: Aldosterone response to AngII LS
description: Change in aldosterone from baseline to after Ang II infusion on a LS diet
arm group label: Afr-Amer non-risk allele
arm group label: Afr-Amer risk allele
arm group label: Cauc non-risk allele
arm group label: Cauc risk allele
intervention type: Other
intervention name: Renal blood flow response to salt
description: Change in renal blood flow: High salt to low salt diet
arm group label: Afr-Amer non-risk allele
arm group label: Afr-Amer risk allele
arm group label: Cauc non-risk allele
arm group label: Cauc risk allele
intervention type: Other
intervention name: Vascular Stiffness
description: Change in vascular stiffness, baseline compared to AngII
arm group label: Afr-Amer non-risk allele
arm group label: Afr-Amer risk allele
arm group label: Cauc non-risk allele
arm group label: Cauc risk allele
criteria: 
gender: All
minimum age: 25 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
citation: Krug AW, Tille E, Sun B, Pojoga L, Williams J, Chamarthi B, Lichtman AH, Hopkins PN, Adler GK, Williams GH. Lysine-specific demethylase-1 modifies the age effect on blood pressure sensitivity to dietary salt intake. Age (Dordr). 2013 Oct;35(5):1809-20. doi: 10.1007/s11357-012-9480-0. Epub 2012 Oct 2.
PMID: 23054827
citation: Williams JS, Chamarthi B, Goodarzi MO, Pojoga LH, Sun B, Garza AE, Raby BA, Adler GK, Hopkins PN, Brown NJ, Jeunemaitre X, Ferri C, Fang R, Leonor T, Cui J, Guo X, Taylor KD, Ida Chen YD, Xiang A, Raffel LJ, Buchanan TA, Rotter JI, Williams GH, Shi Y. Lysine-specific demethylase 1: an epigenetic regulator of salt-sensitive hypertension. Am J Hypertens. 2012 Jul;25(7):812-7. doi: 10.1038/ajh.2012.43. Epub 2012 Apr 26.
PMID: 22534796
citation: Pojoga LH, Williams JS, Yao TM, Kumar A, Raffetto JD, do Nascimento GR, Reslan OM, Adler GK, Williams GH, Shi Y, Khalil RA. Histone demethylase LSD1 deficiency during high-salt diet is associated with enhanced vascular contraction, altered NO-cGMP relaxation pathway, and hypertension. Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H1862-71. doi: 10.1152/ajpheart.00513.2011. Epub 2011 Aug 26.
PMID: 21873498
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Jonathan S. Williams, MD, MMSc
investigator title: Associate Physician, Brigham and Women's Hospital
mesh term: Hypersensitivity
sharing ipd: Yes
ipd description: IPD will be shared first thru the publication of research results in peer-review scientific journals by the study investigator. IPD will be made available upon reasonable request from bona fide research organizations in an effort to provide broader impact and enrich public health knowledge. Research volunteer PHI will not be shared, and all participant data will be de-identified and coded. Only encrypted and secure network exchanges will be used for data transfer. Cost sharing my be required in order prepare datasets.