xml: <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/NCT06016478</url>
    </required_header>
    <id_info>
      <org_study_id>IRB2022-1056</org_study_id>
      <nct_id>NCT06016478</nct_id>
    </id_info>
    <brief_title>The Effect of 4 Weeks of L-Citrulline Supplementation on Macro- and Microvascular Function in Type 2 Diabetes</brief_title>
    <official_title>The Effect of 4 Weeks of L-Citrulline Supplementation on Macro- and Microvascular Function in Type 2 Diabetes</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Texas Tech University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Texas Tech University</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 examine the effect of 4 weeks of Citrulline supplementation&#xD;
        on macro- and microvascular function during acute hyperglycemia in middle-aged and older&#xD;
        adults with type 2 diabetes.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Using a double-blind, randomized, placebo-controlled, and parallel design, middle-aged and&#xD;
        older adults with type 2 diabetes will be randomized to receive either CIT supplementation&#xD;
        (6g/day) or placebo (Microcrystalline Cellulose, 6g/day) for 4 weeks.&#xD;
  &#xD;
        There will be a total of 3 laboratory visits. Visit 1 (screening visit) will take&#xD;
        approximately 1 hour and 30 minutes, visit 2 will take approximately 2 hours and 30 minutes,&#xD;
        and visit 3 will be approximately 3 hours each.&#xD;
  &#xD;
        Visit 1 will measure blood pressure, blood glucose and lipid levels, anthropometry, body&#xD;
        composition, and muscle strengths. Visits 2 and 3 will assess vascular function and glucose&#xD;
        control during fasted and acute hyperglycemia conditions induced by 75g of glucose ingestion.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">May 1, 2023</start_date>
    <completion_date type="Anticipated">July 2024</completion_date>
    <primary_completion_date type="Anticipated">July 2024</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>Double-blind (subject, investigator), randomized, parallel, placebo-controlled</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>Double-blind (subject, investigator), randomized, parallel, placebo-controlled</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Change in macrovascular endothelial function in the fasted condition</measure>
      <time_frame>4 weeks</time_frame>
      <description>Macrovascular endothelial function will be measured using brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in macrovascular endothelial function during acute hyperglycemia</measure>
      <time_frame>4 weeks</time_frame>
      <description>Macrovascular endothelial function will be measured using brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in microvascular endothelial function in the fasted condition</measure>
      <time_frame>4 weeks</time_frame>
      <description>Microvascular endothelial function will be assessed using peripheral arterial tonometry (EndoPAT device) during reactive hyperemia at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in microvascular endothelial function in the fasted condition</measure>
      <time_frame>4 weeks</time_frame>
      <description>Microvascular endothelial function will be assessed using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in microvascular endothelial function during acute hyperglycemia</measure>
      <time_frame>4 weeks</time_frame>
      <description>Microvascular endothelial function will be assessed using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in blood glucose levels in the fasted condition</measure>
      <time_frame>4 weeks</time_frame>
      <description>Blood glucose levels will be measured by finger prick at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in blood glucose levels during acute hyperglycemia</measure>
      <time_frame>4 weeks</time_frame>
      <description>Blood glucose levels will be measured by finger prick at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in central and peripheral arterial stiffness in the fasted condition</measure>
      <time_frame>4 weeks</time_frame>
      <description>Arterial stiffness will be assessed using the central (carotid-femoral) and peripheral (femoral-ankle) pulse wave velocity at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in central and peripheral arterial stiffness during acute hyperglycemia</measure>
      <time_frame>4 weeks</time_frame>
      <description>Arterial stiffness will be assessed using the central (carotid-femoral) and peripheral (femoral-ankle) pulse wave velocity at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in blood pressure in the fasted condition</measure>
      <time_frame>4 weeks</time_frame>
      <description>Brachial and aortic blood pressure will be measured using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Finometer). Blood pressure will be measured at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in blood pressure during acute hyperglycemia</measure>
      <time_frame>4 weeks</time_frame>
      <description>Brachial and aortic blood pressure will be measured using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Finometer). Blood pressure will be measured at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in stroke volume in the fasted condition</measure>
      <time_frame>4 weeks</time_frame>
      <description>Stroke volume will be measured using impedance cardiography (PhysioFlow) at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in stroke volume during acute hyperglycemia</measure>
      <time_frame>4 weeks</time_frame>
      <description>Stroke volume will be measured using impedance cardiography (PhysioFlow) at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in total peripheral resistance in the fasted condition</measure>
      <time_frame>4 weeks</time_frame>
      <description>Total peripheral resistance will be measured using impedance cardiography (PhysioFlow) at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in total peripheral resistance during acute hyperglycemia</measure>
      <time_frame>4 weeks</time_frame>
      <description>Total peripheral resistance will be measured using impedance cardiography (PhysioFlow) at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in body composition</measure>
      <time_frame>4 weeks</time_frame>
      <description>Body composition (fat and lean mass) will be measured at baseline and after 4 weeks of supplementation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in muscle strength</measure>
      <time_frame>4 weeks</time_frame>
      <description>Maximal handgrip strength will be measured using handgrip dynamometer. Leg extension and plantar flexion strength will be measured using the 10RM test at baseline and after 4 weeks of supplementation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in insulin levels</measure>
      <time_frame>4 weeks</time_frame>
      <description>Serum insulin levels will be tested at baseline and after 4 weeks of supplementation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in serum arginine levels</measure>
      <time_frame>4 weeks</time_frame>
      <description>Serum arginine levels will tested at baseline and after 4 weeks of supplementation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in serum arginase activity levels</measure>
      <time_frame>4 weeks</time_frame>
      <description>Serum arginase activity levels will tested at baseline and after 4 weeks of supplementation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in 24-hour ambulatory blood pressure monitoring</measure>
      <time_frame>4 weeks</time_frame>
      <description>Ambulatory blood pressure will be obtained using a monitor during daytime and nighttime on two separate days at baseline and after 4 weeks of supplementation.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">36</enrollment>
    <condition>Type 2 Diabetes</condition>
    <arm_group>
      <arm_group_label>L-citrulline</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>6 grams/day</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Microcrystalline cellulose</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>L-citrulline</intervention_name>
      <description>4 weeks of L-citrulline (6 g/day) in 8 capsules. Supplementation will be ingested daily, half of the doses in the morning and half at night.</description>
      <arm_group_label>L-citrulline</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>4 weeks of microcrystalline cellulose in 8 capsules. Supplementation will be ingested daily, half of the doses in the morning and half at night.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Middle-aged and older women and men between 40-75 years old&#xD;
  &#xD;
            -  A physician diagnosed type 2 diabetes at least 3 months ago&#xD;
  &#xD;
            -  Treated with an oral hypoglycemic medication&#xD;
  &#xD;
            -  Body mass index &lt; 40 kg/m2&#xD;
  &#xD;
            -  Systolic blood pressure &lt; 160 mmHg&#xD;
  &#xD;
            -  Sedentary (defined as &lt; 120 min/week of exercise)&#xD;
  &#xD;
            -  Not currently participating in exercise or dietary interventions for at least 2 months&#xD;
               prior the present study and willing to abstain from participating in those strategies&#xD;
               during the duration of this study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  &lt; 40 years of age and &gt; 65 years of age&#xD;
  &#xD;
            -  Use of medications and/or any supplements that may affect outcome variables (such as&#xD;
               arginine- or citrulline-containing supplements, nitrates, and nitroglycerin)&#xD;
  &#xD;
            -  Body mass index ≥ 40 kg/m2&#xD;
  &#xD;
            -  Systolic blood pressure ≥ 160 mmHg&#xD;
  &#xD;
            -  Recent changes in medications within 3 months&#xD;
  &#xD;
            -  Current smoking any tobacco use&#xD;
  &#xD;
            -  Type 1 diabetes, severe cardiovascular/renal/pulmonary diseases&#xD;
  &#xD;
            -  More than 7 alcoholic drinks/week of consumption&#xD;
  &#xD;
            -  Premenopausal women with an irregular menstrual cycle (oligomenorrhea) or pregnancy&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Arturo Figueroa, Ph.D, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Texas Tech University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Arturo Figueroa, Ph.D, MD</last_name>
      <phone>806-834-5587</phone>
      <email>arturo.figueroa@ttu.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>TTU Kinesiology and Sport Management Building</name>
        <address>
          <city>Lubbock</city>
          <state>Texas</state>
          <zip>79409</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Arturo Figueroa, M.D., Ph.D.</last_name>
        <phone>806-834-5587</phone>
        <email>arturo.figueroa@ttu.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 19, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Texas Tech University</investigator_affiliation>
      <investigator_full_name>Arturo Figueroa</investigator_full_name>
      <investigator_title>Arturo Figueroa, Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Endothelial function</keyword>
    <keyword>Arterial stiffness</keyword>
    <keyword>Hyperglycemia</keyword>
    <keyword>Oral glucose tolerance test</keyword>
    <keyword>Aortic blood pressure</keyword>
    <keyword>Blood glucose</keyword>
    <keyword>Lean mass</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Diabetes Mellitus</mesh_term>
      <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06016478
  org study id: IRB2022-1056
  nct id: NCT06016478
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this study is to examine the effect of 4 weeks of Citrulline supplementation
        on macro- and microvascular function during acute hyperglycemia in middle-aged and older
        adults with type 2 diabetes.
  Using a double-blind, randomized, placebo-controlled, and parallel design, middle-aged and
        older adults with type 2 diabetes will be randomized to receive either CIT supplementation
        (6g/day) or placebo (Microcrystalline Cellulose, 6g/day) for 4 weeks.
  
        There will be a total of 3 laboratory visits. Visit 1 (screening visit) will take
        approximately 1 hour and 30 minutes, visit 2 will take approximately 2 hours and 30 minutes,
        and visit 3 will be approximately 3 hours each.
  
        Visit 1 will measure blood pressure, blood glucose and lipid levels, anthropometry, body
        composition, and muscle strengths. Visits 2 and 3 will assess vascular function and glucose
        control during fasted and acute hyperglycemia conditions induced by 75g of glucose ingestion.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Double-blind (subject, investigator), randomized, parallel, placebo-controlled
  primary purpose: Basic Science
  masking: Double (Participant, Investigator)
  masking description: Double-blind (subject, investigator), randomized, parallel, placebo-controlled
  measure: Change in macrovascular endothelial function in the fasted condition
  time frame: 4 weeks
  description: Macrovascular endothelial function will be measured using brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at baseline and after 4 weeks of supplementation.
  measure: Change in macrovascular endothelial function during acute hyperglycemia
  time frame: 4 weeks
  description: Macrovascular endothelial function will be measured using brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
  measure: Change in microvascular endothelial function in the fasted condition
  time frame: 4 weeks
  description: Microvascular endothelial function will be assessed using peripheral arterial tonometry (EndoPAT device) during reactive hyperemia at baseline and after 4 weeks of supplementation.
  measure: Change in microvascular endothelial function in the fasted condition
  time frame: 4 weeks
  description: Microvascular endothelial function will be assessed using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at baseline and after 4 weeks of supplementation.
  measure: Change in microvascular endothelial function during acute hyperglycemia
  time frame: 4 weeks
  description: Microvascular endothelial function will be assessed using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
  measure: Change in blood glucose levels in the fasted condition
  time frame: 4 weeks
  description: Blood glucose levels will be measured by finger prick at baseline and after 4 weeks of supplementation.
  measure: Change in blood glucose levels during acute hyperglycemia
  time frame: 4 weeks
  description: Blood glucose levels will be measured by finger prick at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
  measure: Change in central and peripheral arterial stiffness in the fasted condition
  time frame: 4 weeks
  description: Arterial stiffness will be assessed using the central (carotid-femoral) and peripheral (femoral-ankle) pulse wave velocity at baseline and after 4 weeks of supplementation.
  measure: Change in central and peripheral arterial stiffness during acute hyperglycemia
  time frame: 4 weeks
  description: Arterial stiffness will be assessed using the central (carotid-femoral) and peripheral (femoral-ankle) pulse wave velocity at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
  measure: Change in blood pressure in the fasted condition
  time frame: 4 weeks
  description: Brachial and aortic blood pressure will be measured using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Finometer). Blood pressure will be measured at baseline and after 4 weeks of supplementation.
  measure: Change in blood pressure during acute hyperglycemia
  time frame: 4 weeks
  description: Brachial and aortic blood pressure will be measured using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Finometer). Blood pressure will be measured at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
  measure: Change in stroke volume in the fasted condition
  time frame: 4 weeks
  description: Stroke volume will be measured using impedance cardiography (PhysioFlow) at baseline and after 4 weeks of supplementation.
  measure: Change in stroke volume during acute hyperglycemia
  time frame: 4 weeks
  description: Stroke volume will be measured using impedance cardiography (PhysioFlow) at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
  measure: Change in total peripheral resistance in the fasted condition
  time frame: 4 weeks
  description: Total peripheral resistance will be measured using impedance cardiography (PhysioFlow) at baseline and after 4 weeks of supplementation.
  measure: Change in total peripheral resistance during acute hyperglycemia
  time frame: 4 weeks
  description: Total peripheral resistance will be measured using impedance cardiography (PhysioFlow) at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
  measure: Change in body composition
  time frame: 4 weeks
  description: Body composition (fat and lean mass) will be measured at baseline and after 4 weeks of supplementation.
  measure: Change in muscle strength
  time frame: 4 weeks
  description: Maximal handgrip strength will be measured using handgrip dynamometer. Leg extension and plantar flexion strength will be measured using the 10RM test at baseline and after 4 weeks of supplementation.
  measure: Change in insulin levels
  time frame: 4 weeks
  description: Serum insulin levels will be tested at baseline and after 4 weeks of supplementation.
  measure: Change in serum arginine levels
  time frame: 4 weeks
  description: Serum arginine levels will tested at baseline and after 4 weeks of supplementation.
  measure: Change in serum arginase activity levels
  time frame: 4 weeks
  description: Serum arginase activity levels will tested at baseline and after 4 weeks of supplementation.
  measure: Change in 24-hour ambulatory blood pressure monitoring
  time frame: 4 weeks
  description: Ambulatory blood pressure will be obtained using a monitor during daytime and nighttime on two separate days at baseline and after 4 weeks of supplementation.
  arm group label: L-citrulline
  arm group type: Experimental
  description: 6 grams/day
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Microcrystalline cellulose
  intervention type: Dietary Supplement
  intervention name: L-citrulline
  description: 4 weeks of L-citrulline (6 g/day) in 8 capsules. Supplementation will be ingested daily, half of the doses in the morning and half at night.
  arm group label: L-citrulline
  intervention type: Dietary Supplement
  intervention name: Placebo
  description: 4 weeks of microcrystalline cellulose in 8 capsules. Supplementation will be ingested daily, half of the doses in the morning and half at night.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: 75 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Arturo Figueroa, Ph.D, MD
  role: Principal Investigator
  affiliation: Texas Tech University
  last name: Arturo Figueroa, Ph.D, MD
  phone: 806-834-5587
  email: arturo.figueroa@ttu.edu
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Texas Tech University
  investigator full name: Arturo Figueroa
  investigator title: Arturo Figueroa, Principal Investigator
  mesh term: Diabetes Mellitus
  mesh term: Diabetes Mellitus, Type 2
  sharing ipd: No