Neuroimaging of Donor Iron Deficient Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Neuroimaging of Donor Iron Deficient Study (DIDS)

Conditions
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Iron Deficiency

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current participant of the associated randomized controlled trial conducted at Columbia University Medical Center (therefore invited to participate in this optional ancillary study). Exclusion Criteria: Not a current participant of the associated randomized controlled trial conducted at Columbia University Medical Center.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Iron Repletion<br>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. | |
| Placebo<br>Subjects participating in the associated study under the Placebo arm will also undergo MRI/fMRI scans on two occasions, while performing cognitive tasks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean iron content in specific brain nuclei | To assess the iron deposition/accumulation in subjects' brain region by using neuroimaging such as MRI/fMRI. | Up to 5 months | 
| Cognition Fluid Composite Score | 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. | Up to 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activity and connectivity in specific functional networks at resting state | 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. | Up to 5 months | 
| Brain activity during tasks of processing speed and episodic memory | 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. | Up to 5 months | 
| NIH Toolbox Auditory Verbal Learning Test (Rey) Score | 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. | Up to 5 months | 
| NIH Toolbox Flanker Inhibitory Control and Attention Test Score | 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. | Up to 5 months | 
| NIH Toolbox List Sorting Working Memory Test Score | 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. | Up to 5 months | 
| NIH Toolbox Dimensional Change Card Sort Test | 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. | Up to 5 months | 
| NIH Toolbox Pattern Comparison Processing Speed Test Score | 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. | Up to 5 months | 
| NIH Toolbox Picture Sequence Memory Test | 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. | Up to 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron repletion, Blood donation, Transfusion