<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/NCT03290612</url>
  </required_header>
  <id_info>
    <org_study_id>IRB 00017294</org_study_id>
    <nct_id>NCT03290612</nct_id>
  </id_info>
  <brief_title>Vitamin C to Reduce Morning Cardiovascular Risk</brief_title>
  <official_title>Chronotherapeutic Use of Vitamin C to Reduce Morning Cardiovascular Risk</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oregon Health and Science 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>
      This study will test the efficacy of Vitamin C to counteract morning cardiovascular (CV) risk&#xD;
      markers in a randomized, double blind, placebo controlled crossover pilot study. The&#xD;
      participants will also perform morning typical behaviors such as arousal from sleep, change&#xD;
      in posture (getting out of bed) and mild intensity physical activity; identical to the&#xD;
      stressors encountered in everyday life. Primary dependent variables are markers of&#xD;
      cardiovascular risk including vascular endothelial function and oxidative stress.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators plan to test the efficacy of Vitamin C to counteract morning cardiovascular&#xD;
      (CV) risk markers in a randomized, double blind, placebo controlled crossover pilot study.&#xD;
      The participants will also perform morning typical behaviors such as arousal from sleep,&#xD;
      change in posture (getting out of bed) and mild intensity physical activity; identical to the&#xD;
      stressors encountered in everyday life. This pilot study is in healthy middle aged adults&#xD;
      without a history of CV disease.&#xD;
&#xD;
      Participants will spend two nights in an inpatient hospital suite at Hatfield Research&#xD;
      Center. Upon awakening in the morning, they will either ingest Vitamin C or placebo in a&#xD;
      randomized order. This will be followed by moderate intensity exercise, recovery, and&#xD;
      discharge.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 13, 2018</start_date>
  <completion_date type="Actual">March 1, 2022</completion_date>
  <primary_completion_date type="Actual">March 1, 2022</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>Crossover Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Vitamin C and Placebo doses will be blinded by the research pharmacy, so that participants and investigators are masked to the identity of the tablet. Data analysis will be blinded to the conditions as well until the completion of the study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Vascular Endothelial Function</measure>
    <time_frame>Approximately three months</time_frame>
    <description>Vascular endothelial function will be measured as flow-mediated dilation (FMD). We will measure brachial artery FMD immediately upon awakening in a constant posture following an overnight fast using the standard guidelines and protocol.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Oxidative stress</measure>
    <time_frame>Approximately three months</time_frame>
    <description>Oxidative stress will be measured as malondialdehyde (MDA) adducts from Ethylenediaminetetraacetic acid (EDTA) plasma. Higher values may indicate increased oxidative stress.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma Vitamin C and Tetrahydrobiopterin</measure>
    <time_frame>Approximately three months</time_frame>
    <description>We will measure Vitamin C levels in the plasma to ensure that the levels are increased after supplementation, and to control for baseline levels. We will measure tetrahydrobiopterin (BH4) from plasma to test if levels are increased upon administration of Vitamin C.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Platelet aggregation</measure>
    <time_frame>Approximately three months</time_frame>
    <description>Platelet aggregation will be measured using Chronolog 560 VS Platelet aggregometer as an indicator of how well blood clots or clumps together. Higher values may indicate increased cardiovascular risk.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasminogen activator inhibitor -1</measure>
    <time_frame>Approximately three months</time_frame>
    <description>Plasminogen activator inhibitor-1 (PAI-1) will be measured from plasma as a blood inflammatory marker. Higher values may indicate increased cardiovascular risk.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Cardiovascular Risk Factor</condition>
  <arm_group>
    <arm_group_label>Vitamin C then Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a 1.5g dose of Ascorbic Acid upon wake for the first visit, and a placebo tablet on the second visit.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo then Vitamin C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a placebo tablet upon wake for the first visit, and a 1.5g dose of Ascorbic Acid on the second visit.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin C</intervention_name>
    <description>1.5g Ascorbic Acid</description>
    <arm_group_label>Placebo then Vitamin C</arm_group_label>
    <arm_group_label>Vitamin C then Placebo</arm_group_label>
    <other_name>Ascorbic Acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Inactive placebo to mimic 1.5g ascorbic acid.</description>
    <arm_group_label>Placebo then Vitamin C</arm_group_label>
    <arm_group_label>Vitamin C then Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy participants&#xD;
&#xD;
          -  Normal weight or overweight but not obese (18.5&lt;BMI&lt;33 kg/m2)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of smoking/tobacco use&#xD;
&#xD;
          -  Current prescription/non-prescription medications or drugs of abuse&#xD;
&#xD;
          -  Acute, chronic, or debilitating medical conditions&#xD;
&#xD;
          -  History of working irregular day and night hours, regular night work, or rotating&#xD;
             shift work for the six months prior to the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Saurabh S Thosar, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oregon Health and Science University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>March 21, 2023</last_update_submitted>
  <last_update_submitted_qc>March 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oregon Health and Science University</investigator_affiliation>
    <investigator_full_name>Steven A. Shea</investigator_full_name>
    <investigator_title>Director, Oregon Institute of Occupational Health Sciences</investigator_title>
  </responsible_party>
  <keyword>Sleep</keyword>
  <keyword>Vitamin C</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ascorbic Acid</mesh_term>
  </intervention_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/NCT03290612
org study id: IRB 00017294
nct id: NCT03290612
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will test the efficacy of Vitamin C to counteract morning cardiovascular (CV) risk
      markers in a randomized, double blind, placebo controlled crossover pilot study. The
      participants will also perform morning typical behaviors such as arousal from sleep, change
      in posture (getting out of bed) and mild intensity physical activity; identical to the
      stressors encountered in everyday life. Primary dependent variables are markers of
      cardiovascular risk including vascular endothelial function and oxidative stress.
The investigators plan to test the efficacy of Vitamin C to counteract morning cardiovascular
      (CV) risk markers in a randomized, double blind, placebo controlled crossover pilot study.
      The participants will also perform morning typical behaviors such as arousal from sleep,
      change in posture (getting out of bed) and mild intensity physical activity; identical to the
      stressors encountered in everyday life. This pilot study is in healthy middle aged adults
      without a history of CV disease.

      Participants will spend two nights in an inpatient hospital suite at Hatfield Research
      Center. Upon awakening in the morning, they will either ingest Vitamin C or placebo in a
      randomized order. This will be followed by moderate intensity exercise, recovery, and
      discharge.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Vitamin C and Placebo doses will be blinded by the research pharmacy, so that participants and investigators are masked to the identity of the tablet. Data analysis will be blinded to the conditions as well until the completion of the study.
measure: Vascular Endothelial Function
time frame: Approximately three months
description: Vascular endothelial function will be measured as flow-mediated dilation (FMD). We will measure brachial artery FMD immediately upon awakening in a constant posture following an overnight fast using the standard guidelines and protocol.
measure: Oxidative stress
time frame: Approximately three months
description: Oxidative stress will be measured as malondialdehyde (MDA) adducts from Ethylenediaminetetraacetic acid (EDTA) plasma. Higher values may indicate increased oxidative stress.
measure: Plasma Vitamin C and Tetrahydrobiopterin
time frame: Approximately three months
description: We will measure Vitamin C levels in the plasma to ensure that the levels are increased after supplementation, and to control for baseline levels. We will measure tetrahydrobiopterin (BH4) from plasma to test if levels are increased upon administration of Vitamin C.
measure: Platelet aggregation
time frame: Approximately three months
description: Platelet aggregation will be measured using Chronolog 560 VS Platelet aggregometer as an indicator of how well blood clots or clumps together. Higher values may indicate increased cardiovascular risk.
measure: Plasminogen activator inhibitor -1
time frame: Approximately three months
description: Plasminogen activator inhibitor-1 (PAI-1) will be measured from plasma as a blood inflammatory marker. Higher values may indicate increased cardiovascular risk.
arm group label: Vitamin C then Placebo
arm group type: Experimental
description: Participants will receive a 1.5g dose of Ascorbic Acid upon wake for the first visit, and a placebo tablet on the second visit.
arm group label: Placebo then Vitamin C
arm group type: Experimental
description: Participants will receive a placebo tablet upon wake for the first visit, and a 1.5g dose of Ascorbic Acid on the second visit.
intervention type: Dietary Supplement
intervention name: Vitamin C
description: 1.5g Ascorbic Acid
arm group label: Placebo then Vitamin C
arm group label: Vitamin C then Placebo
other name: Ascorbic Acid
intervention type: Other
intervention name: Placebo
description: Inactive placebo to mimic 1.5g ascorbic acid.
arm group label: Placebo then Vitamin C
arm group label: Vitamin C then Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Saurabh S Thosar, PhD
role: Principal Investigator
affiliation: Oregon Health and Science University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Oregon Health and Science University
investigator full name: Steven A. Shea
investigator title: Director, Oregon Institute of Occupational Health Sciences
mesh term: Ascorbic Acid
sharing ipd: No