<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/NCT03775382</url>
  </required_header>
  <id_info>
    <org_study_id>Martens - 1138735</org_study_id>
    <nct_id>NCT03775382</nct_id>
  </id_info>
  <brief_title>Mechanisms of Impaired Brain Blood Flow With Aging</brief_title>
  <official_title>Mechanisms of Impaired Brain Blood Flow With Aging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Delaware</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Delaware</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>
      Aging is the primary risk factor for Alzheimer's disease (AD), which is a rapidly growing&#xD;
      public health concern. Understanding the mechanisms of normal brain aging may provide insight&#xD;
      into the factors linking advancing age to increased risk for AD and thereby lead to new&#xD;
      therapeutic targets for preventing or slowing AD progression. Cardiovascular changes,&#xD;
      including impaired cerebrovascular function, occur with aging and may increase risk for AD;&#xD;
      however, the mechanisms by which cerebrovascular function becomes impaired in older adults&#xD;
      are incompletely understood. The overall goal of this project is to examine potential&#xD;
      mechanisms of age-related declines in cerebrovascular function in humans. The investigators&#xD;
      hypothesize that brain macro-vascular endothelial dysfunction, secondary to oxidative stress,&#xD;
      plays an important role in mediating age-related changes in brain blood flow and&#xD;
      cerebrovascular reactivity. The results of this pilot study have the potential to identify&#xD;
      novel targets of cerebrovascular aging and will help guide the design of future clinical&#xD;
      trials aimed at improving cerebral blood flow in older adults.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 30, 2017</start_date>
  <completion_date type="Actual">June 1, 2022</completion_date>
  <primary_completion_date type="Actual">June 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>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in internal carotid artery (ICA) diameter after acute infusion of the antioxidant ascorbic acid</measure>
    <time_frame>Change from baseline to 30 minutes post-infusion</time_frame>
    <description>Cerebrovascular reactivity to hypercapnia</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in middle cerebral artery (MCA) diameter after acute infusion of the antioxidant ascorbic acid</measure>
    <time_frame>Change from baseline to 30 minutes post-infusion</time_frame>
    <description>Cerebrovascular reactivity to hypercapnia</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Aging</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline will be infused by the research nurse into an antecubital vein using an IV infusion pump.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ascorbic Acid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ascorbic acid will be measured into sterile syringes by the research nurse and infused into an antecubital vein using a IV infusion pump beginning with a priming bolus of 0.06 g Ascorbic Acid per kg fat-free mass dissolved in 100 ml of saline or lactated ringers followed by a &quot;drip-infusion&quot; of 0.02 g Ascorbic Acid per kg fat-free mass dissolved in 30 ml of saline.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ascorbic Acid</intervention_name>
    <description>Ascorbic acid will be infused into an antecubital vein using a IV infusion pump beginning with a priming bolus of 0.06 g Ascorbic Acid per kg fat-free mass dissolved in 100 ml of saline followed by a &quot;drip-infusion&quot; of 0.02 g Ascorbic Acid per kg fat-free mass dissolved in 30 ml of saline.</description>
    <arm_group_label>Ascorbic Acid</arm_group_label>
    <other_name>Vitamin C</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Normal Saline</intervention_name>
    <description>Normal saline will be infused by the research nurse into an antecubital vein using an IV infusion pump.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-29 or 55-79 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or breastfeeding;&#xD;
&#xD;
          -  Blood chemistries indicative of abnormal renal, liver, thyroid and adrenal function&#xD;
             (i.e., outside of normal reference range); estimated glomerular filtration rate using&#xD;
             the MDRD prediction equation must be &gt;60 ml/min/1.73 m2;&#xD;
&#xD;
          -  Abnormal blood chemistry that is clinically relevant or any blood chemistry marker&#xD;
             that is +/-2.5x the upper or lower limit;&#xD;
&#xD;
          -  Lack of a suitable temporal window for cerebrovascular assessments;&#xD;
&#xD;
          -  Current smoking;&#xD;
&#xD;
          -  Chronic clinical diseases (e.g., coronary artery, peripheral artery, or&#xD;
             cerebrovascular diseases, diabetes, chronic kidney disease, COPD);&#xD;
&#xD;
          -  Major psychiatric disorder (e.g. Alzheimer's disease or other form of dementia,&#xD;
             schizophrenia, bipolar disorder, major depression within past two years);&#xD;
&#xD;
          -  Neurological or autoimmune conditions affecting cognition (e.g. Parkinson's disease,&#xD;
             epilepsy, multiple sclerosis, head trauma with loss of consciousness greater than 30&#xD;
             min, large vessel infarct);&#xD;
&#xD;
          -  Current medication use likely to affect CNS functions (e.g. long active&#xD;
             benzodiazepines);&#xD;
&#xD;
          -  Having past or present alcohol dependence or abuse, as defined by the American&#xD;
             Psychiatry Association, Diagnostic and Statistical Manual of Mental Disorders;&#xD;
&#xD;
          -  Body mass index (BMI) &gt;40 kg/m2 (FMD measurements can be inaccurate in severely obese&#xD;
             patients).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher R Martens, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Delaware</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Neurovascular Aging Laboratory</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 12, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 13, 2018</study_first_posted>
  <last_update_submitted>May 8, 2023</last_update_submitted>
  <last_update_submitted_qc>May 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Delaware</investigator_affiliation>
    <investigator_full_name>Christopher Martens</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <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>
  <pending_results>
    <submitted>June 5, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03775382
org study id: Martens - 1138735
nct id: NCT03775382
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Aging is the primary risk factor for Alzheimer's disease (AD), which is a rapidly growing
      public health concern. Understanding the mechanisms of normal brain aging may provide insight
      into the factors linking advancing age to increased risk for AD and thereby lead to new
      therapeutic targets for preventing or slowing AD progression. Cardiovascular changes,
      including impaired cerebrovascular function, occur with aging and may increase risk for AD;
      however, the mechanisms by which cerebrovascular function becomes impaired in older adults
      are incompletely understood. The overall goal of this project is to examine potential
      mechanisms of age-related declines in cerebrovascular function in humans. The investigators
      hypothesize that brain macro-vascular endothelial dysfunction, secondary to oxidative stress,
      plays an important role in mediating age-related changes in brain blood flow and
      cerebrovascular reactivity. The results of this pilot study have the potential to identify
      novel targets of cerebrovascular aging and will help guide the design of future clinical
      trials aimed at improving cerebral blood flow in older adults.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change from baseline in internal carotid artery (ICA) diameter after acute infusion of the antioxidant ascorbic acid
time frame: Change from baseline to 30 minutes post-infusion
description: Cerebrovascular reactivity to hypercapnia
measure: Change from baseline in middle cerebral artery (MCA) diameter after acute infusion of the antioxidant ascorbic acid
time frame: Change from baseline to 30 minutes post-infusion
description: Cerebrovascular reactivity to hypercapnia
arm group label: Placebo
arm group type: Placebo Comparator
description: Normal saline will be infused by the research nurse into an antecubital vein using an IV infusion pump.
arm group label: Ascorbic Acid
arm group type: Active Comparator
description: Ascorbic acid will be measured into sterile syringes by the research nurse and infused into an antecubital vein using a IV infusion pump beginning with a priming bolus of 0.06 g Ascorbic Acid per kg fat-free mass dissolved in 100 ml of saline or lactated ringers followed by a "drip-infusion" of 0.02 g Ascorbic Acid per kg fat-free mass dissolved in 30 ml of saline.
intervention type: Other
intervention name: Ascorbic Acid
description: Ascorbic acid will be infused into an antecubital vein using a IV infusion pump beginning with a priming bolus of 0.06 g Ascorbic Acid per kg fat-free mass dissolved in 100 ml of saline followed by a "drip-infusion" of 0.02 g Ascorbic Acid per kg fat-free mass dissolved in 30 ml of saline.
arm group label: Ascorbic Acid
other name: Vitamin C
intervention type: Other
intervention name: Normal Saline
description: Normal saline will be infused by the research nurse into an antecubital vein using an IV infusion pump.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Christopher R Martens, Ph.D.
role: Principal Investigator
affiliation: University of Delaware
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Delaware
investigator full name: Christopher Martens
investigator title: Assistant Professor
mesh term: Ascorbic Acid
sharing ipd: No
submitted: June 5, 2023