<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/NCT01715844</url>
  </required_header>
  <id_info>
    <org_study_id>L-citrulline Asthma</org_study_id>
    <nct_id>NCT01715844</nct_id>
  </id_info>
  <brief_title>L-Citrulline Supplementation Pilot Study for Overweight Late Onset Asthmatics</brief_title>
  <acronym>SANDIA</acronym>
  <official_title>L-Citrulline Supplementation Pilot Study for Overweight Late Onset Asthmatics</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In people who develop asthma after the age of 12 and who are also overweigh, there can be an&#xD;
      increased burden of asthma symptoms, more flare-ups, and poorly-controlled asthma when&#xD;
      compared to normal weight asthmatics. Certain factors are more abundant in the blood of&#xD;
      individuals who are obese. One such factor is derived from the metabolism of an amino acid&#xD;
      found in your diet, which is known as L-arginine (Amino acids are most commonly known as the&#xD;
      building blocks of proteins, the same as the proteins found in food). This factor is called&#xD;
      asymmetric dimethylarginine or ADMA. The balance of L-arginine to ADMA may be important to&#xD;
      the health of subjects with asthma. The balance between L-arginine and ADMA plays an&#xD;
      important role in producing nitric oxide (NO) in the airways. NO is normally produced in the&#xD;
      lung and plays a major role in maintaining airways open and functioning normally. Our&#xD;
      research has shown that in subjects with asthma who are overweight and developed asthma later&#xD;
      in life, the combination of low L-arginine and high ADMA, may lead to lower NO levels. We are&#xD;
      asking participants in this study to take L-citrulline, which is converted to L-arginine by&#xD;
      your body, as a supplement for a period of one week. We anticipate that L-citrulline will&#xD;
      restore NO levels in the airways, by increasing the ratio of L-arginine to ADMA&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 7, 2013</start_date>
  <completion_date type="Actual">June 1, 2017</completion_date>
  <primary_completion_date type="Actual">June 1, 2016</primary_completion_date>
  <phase>Phase 1</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Exhaled nitric oxide</measure>
    <time_frame>1 week</time_frame>
    <description>Patients will be randomized to 1 week of 3 g of L-citrulline/day vs matching placebo, The outcome is the pre to post intervention change in exhaled NO</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sputum and plasma L-arginine/ADMA levels</measure>
    <time_frame>1 week</time_frame>
    <description>This outcome compares the pre to post L-citrulline supplementation changes in sputum and plasma L-arginine/ADMA</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>L-citrulline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>3-gr/day of L-citrulline effervescent powder mix</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>3 gr of Placebo/day matching L-citrulline effervescent powder</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>L-citrulline</intervention_name>
    <description>Patients will take 3-gr of L-citrulline/day for 7 days</description>
    <arm_group_label>L-citrulline</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>L-citrulline 3 gr efervescent powder</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients, 18-75 yrs old, from all racial/ethnic backgrounds&#xD;
&#xD;
          -  Diagnosis of asthma for &gt;1 yr&#xD;
&#xD;
          -  BMI ≥ 30&#xD;
&#xD;
          -  Baseline pre-bronchodilator FEV1 between 60 and 90% predicted with a 12% or greater&#xD;
             bronchodilator response to 4 puffs of albuterol&#xD;
&#xD;
          -  Smoking history &lt;20 pack years and no smoking in the last year&#xD;
&#xD;
          -  Able to identify age of asthma onset&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Respiratory tract infection within the last 4 weeks;&#xD;
&#xD;
          -  Oral CS burst within the last 4 weeks or regular systemic CS use&#xD;
&#xD;
          -  Hospitalization within the last 3 months&#xD;
&#xD;
          -  ER visit within the 4 weeks&#xD;
&#xD;
          -  Significant or uncontrolled concomitant medical illness including (but not limited to)&#xD;
             heart disease, cancer, diabetes&#xD;
&#xD;
          -  Current smoking or within the previous 12 months&#xD;
&#xD;
          -  Current use of statins for the past 30 days (Statins lower ADMA levels)&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Intolerance or allergy to L-arginine or L-citrulline&#xD;
&#xD;
          -  Phosphodiesterase inhibitors&#xD;
&#xD;
          -  Taking oral nitrates&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fernando Holguin, MD MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Asthma Institute, University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <last_update_submitted>June 29, 2017</last_update_submitted>
  <last_update_submitted_qc>June 29, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Fernando Holguin</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>L-citrulline</keyword>
  <keyword>ADMA</keyword>
  <keyword>Asthma</keyword>
  <keyword>Obesity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Overweight</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/NCT01715844
org study id: L-citrulline Asthma
nct id: NCT01715844
lead sponsor: 
has dmc: Yes
In people who develop asthma after the age of 12 and who are also overweigh, there can be an
      increased burden of asthma symptoms, more flare-ups, and poorly-controlled asthma when
      compared to normal weight asthmatics. Certain factors are more abundant in the blood of
      individuals who are obese. One such factor is derived from the metabolism of an amino acid
      found in your diet, which is known as L-arginine (Amino acids are most commonly known as the
      building blocks of proteins, the same as the proteins found in food). This factor is called
      asymmetric dimethylarginine or ADMA. The balance of L-arginine to ADMA may be important to
      the health of subjects with asthma. The balance between L-arginine and ADMA plays an
      important role in producing nitric oxide (NO) in the airways. NO is normally produced in the
      lung and plays a major role in maintaining airways open and functioning normally. Our
      research has shown that in subjects with asthma who are overweight and developed asthma later
      in life, the combination of low L-arginine and high ADMA, may lead to lower NO levels. We are
      asking participants in this study to take L-citrulline, which is converted to L-arginine by
      your body, as a supplement for a period of one week. We anticipate that L-citrulline will
      restore NO levels in the airways, by increasing the ratio of L-arginine to ADMA
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Exhaled nitric oxide
time frame: 1 week
description: Patients will be randomized to 1 week of 3 g of L-citrulline/day vs matching placebo, The outcome is the pre to post intervention change in exhaled NO
measure: Sputum and plasma L-arginine/ADMA levels
time frame: 1 week
description: This outcome compares the pre to post L-citrulline supplementation changes in sputum and plasma L-arginine/ADMA
arm group label: L-citrulline
arm group type: Active Comparator
description: 3-gr/day of L-citrulline effervescent powder mix
arm group label: Placebo
arm group type: Placebo Comparator
description: 3 gr of Placebo/day matching L-citrulline effervescent powder
intervention type: Dietary Supplement
intervention name: L-citrulline
description: Patients will take 3-gr of L-citrulline/day for 7 days
arm group label: L-citrulline
arm group label: Placebo
other name: L-citrulline 3 gr efervescent powder
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Fernando Holguin, MD MPH
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Fernando Holguin
investigator title: Assistant Professor of Medicine
mesh term: Overweight