<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/NCT03826147</url>
  </required_header>
  <id_info>
    <org_study_id>18-0364</org_study_id>
    <nct_id>NCT03826147</nct_id>
  </id_info>
  <brief_title>Nitrite-boosting Therapy for Improving Physiological Function in Patients With Chronic Kidney Disease</brief_title>
  <official_title>Nitrite-boosting Therapy for Improving Physiological Function in Patients With Chronic Kidney Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Boulder</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Boulder</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Nitric oxide (NO) is an essential molecule in the body that is decreased in patients with&#xD;
      chronic kidney disease (CKD), leading to reductions in vascular, movement (&quot;motor&quot;) and&#xD;
      cognitive functions. This study will determine if daily oral supplementation (3 months) with&#xD;
      a supplement that increases NO in the body, i.e., nitrate-rich beetroot juice, improves&#xD;
      vascular, motor and cognitive function in patients with CKD; this study will also provide&#xD;
      insight into the biological reasons (mechanisms) by which supplementation with nitrate-rich&#xD;
      beetroot juice improves vascular function in these patients. Overall, this research will&#xD;
      provide scientific evidence supporting the use of nitrate-rich beetroot juice for preserving&#xD;
      physiological function and preventing co-morbid clinical conditions and disability in CKD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 1, 2019</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Anticipated">July 2023</primary_completion_date>
  <phase>Phase 4</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>Other</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in vascular endothelial function</measure>
    <time_frame>Baseline, 3 months</time_frame>
    <description>as measured by brachial artery flow-mediated dilation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in aortic stiffness</measure>
    <time_frame>Baseline, 3 months</time_frame>
    <description>as measured by carotid-femoral pulse wave velocity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in oxidative stress-associated suppression of endothelial function assessed as the increase in brachial artery flow-mediated dilation following an ascorbic acid infusion</measure>
    <time_frame>Baseline, 3 months</time_frame>
    <description>The influence of oxidative stress on brachial artery flow-mediated dilation will be determined by infusing a supraphysiological dose of ascorbic acid known to scavenge superoxide or isovolumic saline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in endothelial cell markers of oxidative stress</measure>
    <time_frame>Baseline, 3 months</time_frame>
    <description>Endothelial cell nitrotyrosine levels will be determined</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Motor function composite score</measure>
    <time_frame>Baseline, 3 months</time_frame>
    <description>Multiple domains of motor function (including endurance, strength, dexterity) assessed using the NIH Toolbox Motor Battery (aggregated into one reported value)</description>
  </other_outcome>
  <other_outcome>
    <measure>Fluid cognition composite score</measure>
    <time_frame>Baseline, 3 months</time_frame>
    <description>Multiple domains of cognitive function (including executive function, memory, processing speed) assessed using the NIH Toolbox Cognitive Battery (aggregated into one reported value)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">92</enrollment>
  <condition>Chronic Kidney Disease</condition>
  <arm_group>
    <arm_group_label>Nitrate-rich beetroot juice</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Daily dose of nitrate-rich beetroot juice (70 mL) for 3 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nitrate-depleted beetroot juice</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Daily dose of nitrate-depleted beetroot juice (70 mL) for 3 months. The nitrate-depleted beetroot juice is identical in appearance, taste and caloric content to nitrate-rich beetroot juice, but with nitrate removed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Nitrate-rich beetroot juice</intervention_name>
    <description>Daily supplementation with ~100 kcal of nitrate-rich beetroot juice containing 400 mg of dietary nitrate (James White Drinks, UK).</description>
    <arm_group_label>Nitrate-rich beetroot juice</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Nitrate-depleted beetroot juice</intervention_name>
    <description>Daily supplementation with ~100 kcal of nitrate-depleted beetroot juice (James White Drinks, UK).</description>
    <arm_group_label>Nitrate-depleted beetroot juice</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  CKD stage II-IV (eGFR using the Modification of Diet in Renal Disease (MDRD)&#xD;
             prediction equation 20-90 mL/min/1.73m2; stable renal function in the past 3 months)&#xD;
&#xD;
          -  Ability to give informed consent&#xD;
&#xD;
          -  Albumin &gt; 3.0 g/dL&#xD;
&#xD;
          -  Ability to perform motor and cognitive tests (e.g., can rise from a chair, walk for 6&#xD;
             min, climb 10 stairs)&#xD;
&#xD;
          -  Free from alcohol dependence or abuse, as defined by the American Psychiatry&#xD;
             Association, Diagnostic and Statistical Manual of Mental Disorders (DSM-V)&#xD;
&#xD;
          -  Mini-mental state examination score &gt;21 (rationale: to screen for subjects with major&#xD;
             cognitive impairment)&#xD;
&#xD;
          -  Blood pressure (BP) &gt;100/60 mmHg for past 3 months (rationale: blood pressure below&#xD;
             100/60 mmHg may elevate the normally small risk of hypotension with nitrate&#xD;
             supplementation)&#xD;
&#xD;
          -  Not taking medications that will interfere with administered medications (e.g.,&#xD;
             sildenafil interacts with nitroglycerin)&#xD;
&#xD;
          -  Body mass index (BMI) &lt;40 kg/m2 (vascular function measurements can be inaccurate in&#xD;
             severely obese patients)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Life expectancy &lt;1 year&#xD;
&#xD;
          -  Uncontrolled hypertension, defined as blood pressure &gt; 160/100 mmHg in the past 3&#xD;
             months&#xD;
&#xD;
          -  History of severe liver disease&#xD;
&#xD;
          -  History of severe congestive heart failure (i.e., ejection fraction &lt; 35%)&#xD;
&#xD;
          -  History of hospitalizations within the last 3 months&#xD;
&#xD;
          -  Active infection or antibiotic therapy&#xD;
&#xD;
          -  Warfarin use&#xD;
&#xD;
          -  Vasculitis requiring immunosuppressive therapy within the last year&#xD;
&#xD;
          -  High dietary nitrate intake or current nitrate/nitrite supplementation;&#xD;
             hypersensitivity to nitrates or nitrites&#xD;
&#xD;
          -  Glucose-6-phosphate dehydrogenase deficiency or blood methemoglobin &gt;2%&#xD;
&#xD;
          -  Unwilling to abstain from use of mouthwash or other oral hygiene practices (e.g.,&#xD;
             tongue scraping) outside of teeth brushing that disrupt the oral microbiome and would&#xD;
             interfere with nitrate conversion to nitrite&#xD;
&#xD;
          -  Blood donation within 8 weeks prior to enrolling in the study; unwilling to abstain&#xD;
             from donating blood for 8 weeks after completing the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matthew J Rossman, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Boulder</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hannah Lally</last_name>
    <phone>303-735-6410</phone>
    <email>beetrootstudy@colorado.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Integrative Physiology of Aging Laboratory</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80309</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melanie R Zigler, M.S.</last_name>
      <phone>303-492-2485</phone>
      <email>melanie.connell@colorado.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>January 29, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>May 15, 2023</last_update_submitted>
  <last_update_submitted_qc>May 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Colorado, Boulder</investigator_affiliation>
    <investigator_full_name>Douglas Seals</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</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/NCT03826147
org study id: 18-0364
nct id: NCT03826147
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Nitric oxide (NO) is an essential molecule in the body that is decreased in patients with
      chronic kidney disease (CKD), leading to reductions in vascular, movement ("motor") and
      cognitive functions. This study will determine if daily oral supplementation (3 months) with
      a supplement that increases NO in the body, i.e., nitrate-rich beetroot juice, improves
      vascular, motor and cognitive function in patients with CKD; this study will also provide
      insight into the biological reasons (mechanisms) by which supplementation with nitrate-rich
      beetroot juice improves vascular function in these patients. Overall, this research will
      provide scientific evidence supporting the use of nitrate-rich beetroot juice for preserving
      physiological function and preventing co-morbid clinical conditions and disability in CKD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Double-blind
measure: Change in vascular endothelial function
time frame: Baseline, 3 months
description: as measured by brachial artery flow-mediated dilation
measure: Change in aortic stiffness
time frame: Baseline, 3 months
description: as measured by carotid-femoral pulse wave velocity
measure: Change in oxidative stress-associated suppression of endothelial function assessed as the increase in brachial artery flow-mediated dilation following an ascorbic acid infusion
time frame: Baseline, 3 months
description: The influence of oxidative stress on brachial artery flow-mediated dilation will be determined by infusing a supraphysiological dose of ascorbic acid known to scavenge superoxide or isovolumic saline
measure: Change in endothelial cell markers of oxidative stress
time frame: Baseline, 3 months
description: Endothelial cell nitrotyrosine levels will be determined
measure: Motor function composite score
time frame: Baseline, 3 months
description: Multiple domains of motor function (including endurance, strength, dexterity) assessed using the NIH Toolbox Motor Battery (aggregated into one reported value)
measure: Fluid cognition composite score
time frame: Baseline, 3 months
description: Multiple domains of cognitive function (including executive function, memory, processing speed) assessed using the NIH Toolbox Cognitive Battery (aggregated into one reported value)
arm group label: Nitrate-rich beetroot juice
arm group type: Active Comparator
description: Daily dose of nitrate-rich beetroot juice (70 mL) for 3 months.
arm group label: Nitrate-depleted beetroot juice
arm group type: Placebo Comparator
description: Daily dose of nitrate-depleted beetroot juice (70 mL) for 3 months. The nitrate-depleted beetroot juice is identical in appearance, taste and caloric content to nitrate-rich beetroot juice, but with nitrate removed.
intervention type: Dietary Supplement
intervention name: Nitrate-rich beetroot juice
description: Daily supplementation with ~100 kcal of nitrate-rich beetroot juice containing 400 mg of dietary nitrate (James White Drinks, UK).
arm group label: Nitrate-rich beetroot juice
intervention type: Dietary Supplement
intervention name: Nitrate-depleted beetroot juice
description: Daily supplementation with ~100 kcal of nitrate-depleted beetroot juice (James White Drinks, UK).
arm group label: Nitrate-depleted beetroot juice
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: No
last name: Matthew J Rossman, PhD
role: Principal Investigator
affiliation: University of Colorado, Boulder
last name: Hannah Lally
phone: 303-735-6410
email: beetrootstudy@colorado.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Colorado, Boulder
investigator full name: Douglas Seals
investigator title: Professor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
sharing ipd: No