<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/NCT01713816</url>
  </required_header>
  <id_info>
    <org_study_id>1208M18321</org_study_id>
    <secondary_id>R01AG039396</secondary_id>
    <nct_id>NCT01713816</nct_id>
  </id_info>
  <brief_title>Human Brain Antioxidants During Oxidative Stress</brief_title>
  <official_title>Noninvasive Antioxidant Quantification in the Human Brain Under Oxidative Stress</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Aging (NIA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Antioxidants are important for having a good memory and for smart thinking when people get&#xD;
      old, and that is important for everyone's quality of life. This research will find out if&#xD;
      normal aging and Alzheimer's disease use up brain antioxidants. It will develop a new imaging&#xD;
      tool that can help doctors to stop cognitive decline.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of this proposal is to advance the mission of improving the health and&#xD;
      well-being of older Americans by augmenting ongoing dementia prevention and treatment&#xD;
      initiatives. It undertakes research on dementia associated with both normal aging and AD. A&#xD;
      new scientist will develop a novel and powerful human brain antioxidant assay using&#xD;
      state-of-the art instrumentation. The approach will be translated to the clinical environment&#xD;
      so that it can be disseminated for use with new research. Specifically, the concentrations of&#xD;
      two important antioxidants, ascorbate (Asc) and glutathione (GSH) will be measured&#xD;
      noninvasively in the human brain. One aim is to measure whether a recent finding of lower&#xD;
      brain GSH concentration in the occipital cortex of cognitively normal elder subjects is also&#xD;
      found in the posterior cingulate cortex, and whether human brain Asc homeostasis persists in&#xD;
      both brain regions. A complementary specific aim is to determine whether lower brain GSH&#xD;
      concentration also occurs under the oxidative stress associated with Alzheimer's disease&#xD;
      (AD). At the same time, data measured in subjects with AD have potential to advance this&#xD;
      powerful new technology toward discovering an early stage biomarker. A sub aim is to make&#xD;
      this technology available to a wide range of physicians and investigators. As such, data&#xD;
      processing will be fully automated using commercially available software. This novel&#xD;
      noninvasive technology facilitates a paradigm shift from systemic assays to quantifying&#xD;
      antioxidants directly in the affected brain region. The approach will take advantage of state&#xD;
      of the art 7 T instrumentation while developing analogous methods on a clinical 3 T scanner.&#xD;
      The process of optimizing magnetic resonance spectroscopy (MRS) for quantification of brain&#xD;
      Asc and GSH concentrations necessitated reliable quantification of an extensive neurochemical&#xD;
      profile (i.e. 19 brain metabolites), which includes the four compounds that are typically&#xD;
      observed. Spectra acquired in stimulated echo acquisition mode (STEAM) will be de-convolved&#xD;
      quantitatively into contributions from the metabolites that contribute discernable resonances&#xD;
      using a linear combination model approach (LCModel). Reliable quantification of brain GSH and&#xD;
      Asc concentrations will first be achieved using ultra high field MRS with multiple transmit&#xD;
      coil technology and accompanying radiofrequency (B1) shimming, then translated to a lower&#xD;
      field clinical platform. Successful completion will determine whether low brain glutathione&#xD;
      concentration is widespread in the elder human brain and whether this difference is&#xD;
      exacerbated by AD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2013</start_date>
  <completion_date type="Actual">July 24, 2018</completion_date>
  <primary_completion_date type="Actual">June 1, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Antioxidant in Alzheimers</measure>
    <time_frame>1 year</time_frame>
    <description>Occipital cortex and posterior cingulate ascorbate and glutathione concentration in young and elder patients as well as in patients with AD</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">52</enrollment>
  <condition>Oxidative Stress</condition>
  <condition>Alzheimer's Disease</condition>
  <condition>Aging</condition>
  <arm_group>
    <arm_group_label>Elderly control</arm_group_label>
    <description>Healthy elderly subjects age and gender matched to the AD cohort, predominantly male</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        All data have been accrued for the healthy aging aim, which included healthy people age&#xD;
        18-22 and age 70-89. To study the second aim, 23 patients with AD will be recruited from&#xD;
        the Minneapolis, MN VA medical center. 23 age - and gender- matched controls will be&#xD;
        recruited to study neurodegenerative disease associated demand on the antioxidant system.&#xD;
        We do NOT currently have the resources to screen candidates with AD who are not current&#xD;
        patients at the VA medical center in Minneapolis.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Age and gender match to AD patients: age range 65-89:&#xD;
&#xD;
        note that we anticipate that our patients will be predominantly male, so we are NOT likely&#xD;
        to enroll females for this portion of the study&#xD;
&#xD;
        Exclusion Criteria::&#xD;
&#xD;
        Claustrophobia Implanted metal devices Pregnancy &gt; RDA dietary supplements&#xD;
&#xD;
        ≥ 5 F+V per day Smoking Depression Poor health or systemic illness Medial history of or&#xD;
        evidence for cognitive problems Unstable medication usage Neurological problems Psychiatric&#xD;
        disorder Substance abuse Usage of investigational drugs Inability to complete cognitive&#xD;
        tests written in and calibrated for English speakers Inadequate vision or hearing to&#xD;
        accommodate participation MMSE (dementia) score ≤ 26&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Melissa Terpstra, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 25, 2012</study_first_posted>
  <last_update_submitted>May 1, 2019</last_update_submitted>
  <last_update_submitted_qc>May 1, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glutathione</keyword>
  <keyword>Ascorbate</keyword>
  <keyword>Alzheimer's disease</keyword>
  <keyword>Aging</keyword>
  <keyword>Magnetic Resonance Spectroscopy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</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/NCT01713816
org study id: 1208M18321
secondary id: R01AG039396
nct id: NCT01713816
lead sponsor: 
collaborator: 
has dmc: No
Antioxidants are important for having a good memory and for smart thinking when people get
      old, and that is important for everyone's quality of life. This research will find out if
      normal aging and Alzheimer's disease use up brain antioxidants. It will develop a new imaging
      tool that can help doctors to stop cognitive decline.
The objective of this proposal is to advance the mission of improving the health and
      well-being of older Americans by augmenting ongoing dementia prevention and treatment
      initiatives. It undertakes research on dementia associated with both normal aging and AD. A
      new scientist will develop a novel and powerful human brain antioxidant assay using
      state-of-the art instrumentation. The approach will be translated to the clinical environment
      so that it can be disseminated for use with new research. Specifically, the concentrations of
      two important antioxidants, ascorbate (Asc) and glutathione (GSH) will be measured
      noninvasively in the human brain. One aim is to measure whether a recent finding of lower
      brain GSH concentration in the occipital cortex of cognitively normal elder subjects is also
      found in the posterior cingulate cortex, and whether human brain Asc homeostasis persists in
      both brain regions. A complementary specific aim is to determine whether lower brain GSH
      concentration also occurs under the oxidative stress associated with Alzheimer's disease
      (AD). At the same time, data measured in subjects with AD have potential to advance this
      powerful new technology toward discovering an early stage biomarker. A sub aim is to make
      this technology available to a wide range of physicians and investigators. As such, data
      processing will be fully automated using commercially available software. This novel
      noninvasive technology facilitates a paradigm shift from systemic assays to quantifying
      antioxidants directly in the affected brain region. The approach will take advantage of state
      of the art 7 T instrumentation while developing analogous methods on a clinical 3 T scanner.
      The process of optimizing magnetic resonance spectroscopy (MRS) for quantification of brain
      Asc and GSH concentrations necessitated reliable quantification of an extensive neurochemical
      profile (i.e. 19 brain metabolites), which includes the four compounds that are typically
      observed. Spectra acquired in stimulated echo acquisition mode (STEAM) will be de-convolved
      quantitatively into contributions from the metabolites that contribute discernable resonances
      using a linear combination model approach (LCModel). Reliable quantification of brain GSH and
      Asc concentrations will first be achieved using ultra high field MRS with multiple transmit
      coil technology and accompanying radiofrequency (B1) shimming, then translated to a lower
      field clinical platform. Successful completion will determine whether low brain glutathione
      concentration is widespread in the elder human brain and whether this difference is
      exacerbated by AD.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Antioxidant in Alzheimers
time frame: 1 year
description: Occipital cortex and posterior cingulate ascorbate and glutathione concentration in young and elder patients as well as in patients with AD
arm group label: Elderly control
description: Healthy elderly subjects age and gender matched to the AD cohort, predominantly male
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 65 Years
maximum age: 89 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Melissa Terpstra, PhD
role: Principal Investigator
affiliation: University of Minnesota
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease