<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/NCT02990559</url>
  </required_header>
  <id_info>
    <org_study_id>AAAR0145</org_study_id>
    <nct_id>NCT02990559</nct_id>
  </id_info>
  <brief_title>Neuroimaging of Donor Iron Deficient Study</brief_title>
  <official_title>Neuroimaging of Donor Iron Deficient Study (DIDS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Columbia University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot study is designed to investigate (1) whether getting iron treatment affects iron&#xD;
      in the brain and (2) how getting iron treatment affects brain functions when it is performing&#xD;
      specific cognitive tasks. By cognitive tasks, it means tasks that involve perceiving,&#xD;
      representing, or assessing things. The specific cognitive tasks used here will involve tests&#xD;
      of memory and processing speed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Iron, the most abundant metal in the brain, is vital for multiple cellular processes,&#xD;
      including neurotransmitter synthesis, neuron myelination, and mitochondrial function. In the&#xD;
      United States, of the donors who provided the ~15 million units of red blood cells that were&#xD;
      collected for transfusion, 69% were repeat donors. Although iron deficiency is surprisingly&#xD;
      prevalent in first-time donors, its prevalence is even higher in these particularly&#xD;
      altruistic frequent donors, (i.e., up to 49% and 66% of male and female repeat donors,&#xD;
      respectively), manifested as iron depletion or iron-deficient erythropoiesis. Iron deficiency&#xD;
      from blood donation is associated with fatigue, restless leg syndrome, decreased physical&#xD;
      endurance and work capacity, and impaired concentration, attention, and other neurocognitive&#xD;
      functions; however, these conclusions are not based on definitive studies and have not yet&#xD;
      changed blood donation policy. This study is to collect data through noninvasive procedures&#xD;
      routinely employed in clinical practice to better understand how iron treatment may affect&#xD;
      brain functions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in mean iron content in specific brain nuclei</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>To assess the iron deposition/accumulation in subjects' brain region by using neuroimaging such as MRI/fMRI.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cognition Fluid Composite Score</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>NIH Toolbox derived uncorrected standard composite score, measured at 4 time points (twice pre-randomization and twice post-randomization). The uncorrected standard score will be used, where the normative mean is 100 with a standard deviation of 15.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Activity and connectivity in specific functional networks at resting state</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>Resting state blood oxygen level dependent (BOLD) signals will be assessed by fMRI. Independent component analysis will be used to detect alterations in connectivity in functional networks (e.g., default mode network and visual, sensory/motor, executive control, temporal/parietal, basal ganglia components) in a paired analysis comparing subjects before and after iron repletion versus placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain activity during tasks of processing speed and episodic memory</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>Brain activity patterns during performance of processing speed and episodic memory tasks will be assessed by fMRI and comparisons made from before to after iron repletion versus placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NIH Toolbox Auditory Verbal Learning Test (Rey) Score</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>NIH Toolbox derived uncorrected standard Auditory Verbal Learning test score, measured at 4 time points (twice pre-randomization and twice post-randomization). Delayed and initial scores analyzed separately. The raw score will be used in which a higher number represents more words remembered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NIH Toolbox Flanker Inhibitory Control and Attention Test Score</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>NIH Toolbox derived uncorrected standard Flanker Inhibitory Control and Attention test score (single score), measured at 4 time points (twice pre-randomization and twice post-randomization). The uncorrected standard score will be used, where the normative mean is 100 with a standard deviation of 15.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NIH Toolbox List Sorting Working Memory Test Score</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>NIH Toolbox derived uncorrected standard List Sorting Working Memory test score, measured at 4 time points (twice pre-randomization and twice post-randomization). The uncorrected standard score will be used, where the normative mean is 100 with a standard deviation of 15.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NIH Toolbox Dimensional Change Card Sort Test</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>NIH Toolbox derived uncorrected standard Dimensional Change Card Sort test score, measured at 4 time points (twice pre-randomization and twice post-randomization). The uncorrected standard score will be used, where the normative mean is 100 with a standard deviation of 15.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NIH Toolbox Pattern Comparison Processing Speed Test Score</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>NIH Toolbox derived uncorrected standard Pattern Comparison Processing Speed test score, measured at 4 time points (twice pre-randomization and twice post-randomization). The uncorrected standard score will be used, where the normative mean is 100 with a standard deviation of 15.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NIH Toolbox Picture Sequence Memory Test</measure>
    <time_frame>Up to 5 months</time_frame>
    <description>NIH Toolbox derived uncorrected standard Picture Sequence Memory test score, measured at 4 time points (twice pre-randomization and twice post-randomization). The uncorrected standard score will be used, where the normative mean is 100 with a standard deviation of 15.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">75</enrollment>
  <condition>Iron Deficiency</condition>
  <arm_group>
    <arm_group_label>Iron Repletion</arm_group_label>
    <description>Subjects participating in the associated study under the Iron Repletion arm will also undergo MRI (Magnetic Resonance Imaging) scan/fMRI (functional Magnetic Resonance Imaging) scan on two occasions, while performing cognitive tasks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <description>Subjects participating in the associated study under the Placebo arm will also undergo MRI/fMRI scans on two occasions, while performing cognitive tasks.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects with iron deficiency from blood donation will be recruited over 5 years in the&#xD;
        associated randomized controlled trial conducted at Columbia University Medical Center.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Current participant of the associated randomized controlled trial conducted at&#xD;
             Columbia University Medical Center (therefore invited to participate in this optional&#xD;
             ancillary study).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not a current participant of the associated randomized controlled trial conducted at&#xD;
             Columbia University Medical Center.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eldad Hod, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate Professor of Pathology and Cell Biology, Dept of Pathology&amp;Cell Biology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10023</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Hare D, Ayton S, Bush A, Lei P. A delicate balance: Iron metabolism and diseases of the brain. Front Aging Neurosci. 2013 Jul 18;5:34. doi: 10.3389/fnagi.2013.00034. eCollection 2013.</citation>
    <PMID>23874300</PMID>
  </reference>
  <reference>
    <citation>Smith GA, Fisher SA, Doree C, Roberts DJ. A systematic review of factors associated with the deferral of donors failing to meet low haemoglobin thresholds. Transfus Med. 2013 Oct;23(5):309-20. doi: 10.1111/tme.12046. Epub 2013 Jul 5.</citation>
    <PMID>23829880</PMID>
  </reference>
  <reference>
    <citation>Bialkowski W, Bryant BJ, Schlumpf KS, Wright DJ, Birch R, Kiss JE, D'Andrea P, Cable RG, Spencer BR, Vij V, Mast AE. The strategies to reduce iron deficiency in blood donors randomized trial: design, enrolment and early retention. Vox Sang. 2015 Feb;108(2):178-85. doi: 10.1111/vox.12210. Epub 2014 Dec 3.</citation>
    <PMID>25469720</PMID>
  </reference>
  <reference>
    <citation>Cable RG, Glynn SA, Kiss JE, Mast AE, Steele WR, Murphy EL, Wright DJ, Sacher RA, Gottschall JL, Tobler LH, Simon TL; NHLBI Retrovirus Epidemiology Donor Study-II (REDS-II). Iron deficiency in blood donors: the REDS-II Donor Iron Status Evaluation (RISE) study. Transfusion. 2012 Apr;52(4):702-11. doi: 10.1111/j.1537-2995.2011.03401.x. Epub 2011 Oct 24.</citation>
    <PMID>22023513</PMID>
  </reference>
  <reference>
    <citation>Brittenham GM. Iron deficiency in whole blood donors. Transfusion. 2011 Mar;51(3):458-61. doi: 10.1111/j.1537-2995.2011.03062.x. No abstract available.</citation>
    <PMID>21388389</PMID>
  </reference>
  <reference>
    <citation>Newman B. Iron depletion by whole-blood donation harms menstruating females: the current whole-blood-collection paradigm needs to be changed. Transfusion. 2006 Oct;46(10):1667-81. doi: 10.1111/j.1537-2995.2006.00969.x. No abstract available.</citation>
    <PMID>17002622</PMID>
  </reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>December 9, 2016</study_first_submitted>
  <study_first_submitted_qc>December 9, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 13, 2016</study_first_posted>
  <last_update_submitted>February 14, 2022</last_update_submitted>
  <last_update_submitted_qc>February 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>Eldad Arie Hod</investigator_full_name>
    <investigator_title>Associate Professor of Pathology and Cell Biology, Dept of Pathology&amp;Cell Biology</investigator_title>
  </responsible_party>
  <keyword>Iron repletion</keyword>
  <keyword>Blood donation</keyword>
  <keyword>Transfusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Iron Deficiencies</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/NCT02990559
org study id: AAAR0145
nct id: NCT02990559
lead sponsor: 
has dmc: No
This pilot study is designed to investigate (1) whether getting iron treatment affects iron
      in the brain and (2) how getting iron treatment affects brain functions when it is performing
      specific cognitive tasks. By cognitive tasks, it means tasks that involve perceiving,
      representing, or assessing things. The specific cognitive tasks used here will involve tests
      of memory and processing speed.
Iron, the most abundant metal in the brain, is vital for multiple cellular processes,
      including neurotransmitter synthesis, neuron myelination, and mitochondrial function. In the
      United States, of the donors who provided the ~15 million units of red blood cells that were
      collected for transfusion, 69% were repeat donors. Although iron deficiency is surprisingly
      prevalent in first-time donors, its prevalence is even higher in these particularly
      altruistic frequent donors, (i.e., up to 49% and 66% of male and female repeat donors,
      respectively), manifested as iron depletion or iron-deficient erythropoiesis. Iron deficiency
      from blood donation is associated with fatigue, restless leg syndrome, decreased physical
      endurance and work capacity, and impaired concentration, attention, and other neurocognitive
      functions; however, these conclusions are not based on definitive studies and have not yet
      changed blood donation policy. This study is to collect data through noninvasive procedures
      routinely employed in clinical practice to better understand how iron treatment may affect
      brain functions.
observational model: Other
time perspective: Prospective
measure: Change in mean iron content in specific brain nuclei
time frame: Up to 5 months
description: To assess the iron deposition/accumulation in subjects' brain region by using neuroimaging such as MRI/fMRI.
measure: Cognition Fluid Composite Score
time frame: Up to 5 months
description: NIH Toolbox derived uncorrected standard composite score, measured at 4 time points (twice pre-randomization and twice post-randomization). The uncorrected standard score will be used, where the normative mean is 100 with a standard deviation of 15.
measure: Activity and connectivity in specific functional networks at resting state
time frame: Up to 5 months
description: Resting state blood oxygen level dependent (BOLD) signals will be assessed by fMRI. Independent component analysis will be used to detect alterations in connectivity in functional networks (e.g., default mode network and visual, sensory/motor, executive control, temporal/parietal, basal ganglia components) in a paired analysis comparing subjects before and after iron repletion versus placebo.
measure: Brain activity during tasks of processing speed and episodic memory
time frame: Up to 5 months
description: Brain activity patterns during performance of processing speed and episodic memory tasks will be assessed by fMRI and comparisons made from before to after iron repletion versus placebo.
measure: NIH Toolbox Auditory Verbal Learning Test (Rey) Score
time frame: Up to 5 months
description: NIH Toolbox derived uncorrected standard Auditory Verbal Learning test score, measured at 4 time points (twice pre-randomization and twice post-randomization). Delayed and initial scores analyzed separately. The raw score will be used in which a higher number represents more words remembered.
measure: NIH Toolbox Flanker Inhibitory Control and Attention Test Score
time frame: Up to 5 months
description: NIH Toolbox derived uncorrected standard Flanker Inhibitory Control and Attention test score (single score), measured at 4 time points (twice pre-randomization and twice post-randomization). The uncorrected standard score will be used, where the normative mean is 100 with a standard deviation of 15.
measure: NIH Toolbox List Sorting Working Memory Test Score
time frame: Up to 5 months
description: NIH Toolbox derived uncorrected standard List Sorting Working Memory test score, measured at 4 time points (twice pre-randomization and twice post-randomization). The uncorrected standard score will be used, where the normative mean is 100 with a standard deviation of 15.
measure: NIH Toolbox Dimensional Change Card Sort Test
time frame: Up to 5 months
description: NIH Toolbox derived uncorrected standard Dimensional Change Card Sort test score, measured at 4 time points (twice pre-randomization and twice post-randomization). The uncorrected standard score will be used, where the normative mean is 100 with a standard deviation of 15.
measure: NIH Toolbox Pattern Comparison Processing Speed Test Score
time frame: Up to 5 months
description: NIH Toolbox derived uncorrected standard Pattern Comparison Processing Speed test score, measured at 4 time points (twice pre-randomization and twice post-randomization). The uncorrected standard score will be used, where the normative mean is 100 with a standard deviation of 15.
measure: NIH Toolbox Picture Sequence Memory Test
time frame: Up to 5 months
description: NIH Toolbox derived uncorrected standard Picture Sequence Memory test score, measured at 4 time points (twice pre-randomization and twice post-randomization). The uncorrected standard score will be used, where the normative mean is 100 with a standard deviation of 15.
arm group label: Iron Repletion
description: Subjects participating in the associated study under the Iron Repletion arm will also undergo MRI (Magnetic Resonance Imaging) scan/fMRI (functional Magnetic Resonance Imaging) scan on two occasions, while performing cognitive tasks.
arm group label: Placebo
description: Subjects participating in the associated study under the Placebo arm will also undergo MRI/fMRI scans on two occasions, while performing cognitive tasks.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Eldad Hod, MD
role: Principal Investigator
affiliation: Associate Professor of Pathology and Cell Biology, Dept of Pathology&Cell Biology
facility: 
country: United States
citation: Hare D, Ayton S, Bush A, Lei P. A delicate balance: Iron metabolism and diseases of the brain. Front Aging Neurosci. 2013 Jul 18;5:34. doi: 10.3389/fnagi.2013.00034. eCollection 2013.
PMID: 23874300
citation: Smith GA, Fisher SA, Doree C, Roberts DJ. A systematic review of factors associated with the deferral of donors failing to meet low haemoglobin thresholds. Transfus Med. 2013 Oct;23(5):309-20. doi: 10.1111/tme.12046. Epub 2013 Jul 5.
PMID: 23829880
citation: Bialkowski W, Bryant BJ, Schlumpf KS, Wright DJ, Birch R, Kiss JE, D'Andrea P, Cable RG, Spencer BR, Vij V, Mast AE. The strategies to reduce iron deficiency in blood donors randomized trial: design, enrolment and early retention. Vox Sang. 2015 Feb;108(2):178-85. doi: 10.1111/vox.12210. Epub 2014 Dec 3.
PMID: 25469720
citation: Cable RG, Glynn SA, Kiss JE, Mast AE, Steele WR, Murphy EL, Wright DJ, Sacher RA, Gottschall JL, Tobler LH, Simon TL; NHLBI Retrovirus Epidemiology Donor Study-II (REDS-II). Iron deficiency in blood donors: the REDS-II Donor Iron Status Evaluation (RISE) study. Transfusion. 2012 Apr;52(4):702-11. doi: 10.1111/j.1537-2995.2011.03401.x. Epub 2011 Oct 24.
PMID: 22023513
citation: Brittenham GM. Iron deficiency in whole blood donors. Transfusion. 2011 Mar;51(3):458-61. doi: 10.1111/j.1537-2995.2011.03062.x. No abstract available.
PMID: 21388389
citation: Newman B. Iron depletion by whole-blood donation harms menstruating females: the current whole-blood-collection paradigm needs to be changed. Transfusion. 2006 Oct;46(10):1667-81. doi: 10.1111/j.1537-2995.2006.00969.x. No abstract available.
PMID: 17002622
responsible party type: Principal Investigator
investigator affiliation: Columbia University
investigator full name: Eldad Arie Hod
investigator title: Associate Professor of Pathology and Cell Biology, Dept of Pathology&Cell Biology
mesh term: Iron Deficiencies
sharing ipd: No