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Iron Deficiency Anemia (IDA)

Primary Purpose

IDA - Iron Deficiency Anemia, Anemia, Iron Deficiency Anemia

Status
Not yet recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ferric carboxymaltose
ferrous sulfate
Sponsored by
Children's Hospital Los Angeles
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for IDA - Iron Deficiency Anemia

Eligibility Criteria

16 Years - 60 Years (Child, Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria: Observational arm: Age between 16 and 60 years of age. Any ethnicity. Female Anemic group: hemoglobin ≤10.5 g/dl or hematocrit <32% from finger prick or plethysmography test, or <11 g/dl from venipuncture blood draw Control group: hemoglobin >13.2 g/dl or hematocrit >39.6% Interventional arm: Criteria for observational component, plus Iron deficiency anemia based upon attending hematologist interpretation of transferrin saturation, ferritin, and other ancillary labs including hs-CRP, MMA, hemoglobin electrophoresis Exclusion Criteria: Observational arm: Diabetes requiring medication. Hypertension requiring medication. Sleep disordered breathing requiring intervention. Body mass index >40 (morbid obesity) Contraindications to MRI, including pacemaker, severe claustrophobia, pregnancy. Known systemic inflammatory disease such as inflammatory bowel disease, systemic lupus erythematosus, or scleroderma. Known HIV. Interventional arm: Criteria for observational component, plus Prior reaction to intravenous iron. History of multiple drug allergies. History of severe asthma, eczema, or atopy. Systemic mastocytosis. Severe respiratory or cardiac disease.

Sites / Locations

  • City of Hope Blood Donor Center
  • Cedar Sinai Blood Bank
  • Children's Hospital Los Angeles
  • University of California, Los Angeles Blood Donor Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Other

No Intervention

Arm Label

Intravenous (IV) iron

Standard of care iron

Healthy Controls

Arm Description

This group will receive intravenous iron (ferric carboxymaltose), which consists of two doses of 15 mg/g given (max individual dose 750 mg) at least seven days apart. The drug is administered as an infusion over 30 minutes

This group will be referred to their primary care provider for oral iron therapy. If a participant cannot obtain care from a physician, the hematology team will call in a prescription for oral ferrous sulfate, 325 mg, taken once a day for 12 weeks.

This group will only be participating in the observational part of the study and serve as our controls.

Outcomes

Primary Outcome Measures

Impact of iron deficiency anemia on regional cerebrovascular oxygen delivery (ml O2/100g/min).
Baseline impact of iron deficiency anemia on cerebrovascular oxygen delivery will be assessed by measuring cerebral blood flow and oxygen content through MRI (time-encoded arterial spin labelling) and peripheral blood sample
Impact of iron therapy on regional cerebrovascular oxygen delivery (ml O2/100g/min) in iron deficiency anemia at day 90 post therapy
Impact of iron therapy on cerebrovascular oxygen delivery will be assessed at day 90 by measuring cerebral blood flow and oxygen content through MRI (time-encoded arterial spin labelling) and peripheral blood sample in people with iron deficiency anemia.
Impact of iron therapy on regional cerebrovascular oxygen delivery (ml O2/100g/min) in iron deficiency anemia at day 365 post therapy.
Impact of iron therapy on cerebrovascular oxygen delivery will be assessed at day 365 by measuring cerebral blood flow and oxygen content through MRI (time-encoded arterial spin labelling) and peripheral blood sample in people with iron deficiency anemia
Impact of iron deficiency anemia on cerebrovascular flow reactivity (%SI change/%ETCO2)
baseline MRI with blood oxygenation level dependent (BOLD) acquisition will be assessed in response to carbon dioxide exposure to determine whether iron deficiency anemia affects cerebrovascular reserve
Impact of iron therapy on cerebrovascular flow reactivity (%SI change/%ETCO2) in people with iron deficiency anemia at 90 days post iron therapy.
Impact of iron therapy on cardiovascular reserve in iron deficiency anemia will be assessed using MRI with blood oxygenation level dependent (BOLD) acquisition at 90 days post iron therapy.
Impact of iron therapy on cerebrovascular flow reactivity (%SI change/%ETCO2) in people with iron deficiency anemia at day 365.
Impact of iron therapy on cardiovascular reserve in iron deficiency anemia will be assessed using MRI with blood oxygenation level dependent (BOLD) acquisition at day 365 post iron therapy.
Impact of iron deficiency anemia on blood brain barrier permeability surface area product (ml H20/100g/min)
baseline PSA product using water-extraction-with phase- contrast-arterial-spin-tagging (WEPCAST) MRI will be assessed to determine whether iron deficiency anemia affects blood brain barrier permeability to water
Impact of iron therapy on blood brain barrier permeability surface area product (ml H20/100g/min) in iron deficiency anemia will be assessed at 90 days.
PSA product using water-extraction-with phase- contrast-arterial-spin-tagging (WEPCAST) MRI will be assessed at 90 days post iron therapy to determine the impact of iron therapy on blood brain barrier permeability to water in patients with iron deficiency anemia.
Impact of iron therapy on blood brain barrier permeability surface area product (ml H20/100g/min) in iron deficiency anemia will be assessed again at day 365.
PSA product using water-extraction-with phase- contrast-arterial-spin-tagging (WEPCAST) MRI will be assessed at 365 days post iron therapy to determine the impact of iron therapy on blood brain barrier permeability to water in patients with iron deficiency anemia.
Impact of iron deficiency anemia on cerebral metabolic rate of oxygen (ml O2/100g/min).
Baseline T2 relaxation under spin tagging (TRUST) acquisition via MRI will be used to assess any impact of iron deficiency anemia on cerebral metabolic rate of oxygen
Impact of iron therapy on cerebral metabolic rate of oxygen (ml O2/100g/min) in people with iron deficiency anemia at day 90 post iron therapy.
T2 relaxation under spin tagging (TRUST) acquisition via MRI will be used to assess any impact of iron therapy on cerebral metabolic rate of oxygen in anemic subjects at day 90.
Impact of iron therapy on cerebral metabolic rate of oxygen (ml O2/100g/min) in people with iron deficiency anemia at day 365 post iron therapy.
T2 relaxation under spin tagging (TRUST) acquisition via MRI will be used to assess any impact of iron therapy on cerebral metabolic rate of oxygen in anemic subjects at day 365.
Impact of iron deficiency anemia on total brain blood flow (ml blood/100g/min).
Phase contrast MRI will be assessed to determine whether iron deficiency anemia affects total brain blood flow at baseline
Impact of iron therapy on total brain blood flow (ml blood/100g/min) in people with iron deficiency anemia at day 90
Phase contrast MRI will be assessed at day 90 post iron therapy to determine whether iron therapy affects total brain blood flow in subjects with iron deficiency anemia
Impact of iron therapy on total brain blood flow (ml blood/100g/min) in people with iron deficiency anemia at day 365
Phase contrast MRI will be assessed at day 365 post iron therapy to determine whether iron therapy affects total brain blood flow in subjects with iron deficiency anemia
Impact of iron deficiency anemia on visual-motor integration.
Visual-motor integration at baseline (day 0) will be assessed using Beery Buktenica Developmental Test of Visual-Motor Integration (6th Edition). Standardized scores with a mean of 100 and a standard deviation of 15 are used. Higher scores mean better performance.
Impact of iron therapy on visual-motor integration in people with iron deficiency anemia.
Visual-motor integration will be assessed using Beery Buktenica Developmental Test of Visual-Motor Integration (6th Edition) at day 365 post iron-therapy. Standardized scores with a mean of 100 and a standard deviation of 15 are used. Higher scores mean better performance.
Impact of iron deficiency anemia on sustained attention.
Sustained attention at baseline (day 0) will be assessed using Conners' Continuous Performance Test (3rd Edition) at day 90 post iron-therapy. T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean worse performance.
Impact of iron therapy on sustained attention in people with iron deficiency anemia.
Sustained attention will be assessed using Conners' Continuous Performance Test (3rd Edition) at day 365 post iron-therapy. T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean worse performance.
Impact of iron deficiency anemia on working memory function.
Working memory function at baseline (day 0) will be assessed using Digit Span, Coding, and Symbol Search Subtests from Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV). Scaled scores with a mean of 10 and a standard deviation of 3 are used. Higher scores mean better performance.
Impact of iron therapy on working memory function in people with iron deficiency anemia.
Working memory function will be assessed at day 365 post iron therapy using Digit Span, Coding, and Symbol Search Subtests from Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV). Scaled scores with a mean of 10 and a standard deviation of 3 are used. Higher scores mean better performance.
Impact of iron deficiency anemia on the ability to inhibit cognitive interference
The ability to inhibit cognitive interference at baseline (day 0) will be assessed using Color-Word Interference Subtest from the Delis-Kaplan Executive Function System (D-KEFS). Scaled scores with a mean of 10 and a standard deviation of 3 are used. Higher scores mean better performance.
Impact of iron therapy on the ability to inhibit cognitive interference in people with iron deficiency anemia.
The ability to inhibit cognitive interference at day 365 post iron therapy will be assessed using Color-Word Interference Subtest from the Delis-Kaplan Executive Function System (D-KEFS). Scaled scores with a mean of 10 and a standard deviation of 3 are used. Higher scores mean better performance.
Impact of iron deficiency anemia on fine motor control.
Fine motor control will be assessed at baseline (day 0) using Reitan Finger Tapping. Z scores with a mean of zero and a standard deviation of one are used. Higher scores mean better performance.
Impact of iron therapy on fine motor control in people with iron deficiency anemia.
Fine motor control will be assessed at day 365 post iron therapy using Reitan Finger Tapping. Z scores with a mean of zero and a standard deviation of one are used. Higher scores mean better performance.
Impact of iron therapy on list learning and recall task in people with iron deficiency anemia.
List learning and recall task will be assessed at day 365 post iron therapy using California Verbal Learning Test-Third Edition (CVLT-3). Z scores with a mean of zero and a standard deviation of 1 are used. Higher scores mean better performance.
Impact of iron deficiency anemia on visuospatial memory
Visuospatial memory will be assessed at baseline (day 0) using Brief Visuospatial Memory Test-Revised (BVMT-R). T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean better performance.
Impact of iron therapy on visuospatial memory in people with iron deficiency anemia.
Visuospatial memory will be assessed at day 365 post iron therapy using Brief Visuospatial Memory Test-Revised (BVMT-R). T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean better performance.
Impact of iron deficiency anemia on general intellectual functioning, verbal and nonverbal abilities.
General intellectual functioning, verbal and nonverbal abilities will be assessed at baseline (day 0) using Wechsler Abbreviated Scale of Intelligence-Second Edition (WASI-2). T scores with a mean of 50 and a standard deviation of 10 are used for the subtests, with standard scores (mean of 100 and standard deviation of 15) used for composite scores. Higher scores mean better performance.
Impact of iron therapy on general intellectual functioning, verbal and nonverbal abilities in people with iron deficiency anemia.
General intellectual functioning, verbal and nonverbal abilities will be assessed at day 365 post iron therapy using Wechsler Abbreviated Scale of Intelligence-Second Edition (WASI-2). T scores with a mean of 50 and a standard deviation of 10 are used for the subtests, with standard scores (mean of 100 and standard deviation of 15) used for composite scores. Higher scores mean better performance.
Impact of iron deficiency anemia on cognitive flexibility and processing speed.
Cognitive flexibility and processing speed will be assessed at baseline (day 0) using NIH Toolbox: Dimensional Change Card Sort and Pattern Comparison Processing Speed. Standard scores with a mean of 100 and a standard deviation of 15 are used. Higher scores mean better performance.
Impact of iron therapy on cognitive flexibility and processing speed in people with iron deficiency anemia.
Cognitive flexibility and processing speed will be assessed at day 365 post iron therapy using NIH Toolbox: Dimensional Change Card Sort and Pattern Comparison Processing Speed. Standard scores with a mean of 100 and a standard deviation of 15 are used. Higher scores mean better performance.
Impact of iron deficiency anemia on list learning and recall task
List learning and recall task will be assessed at baseline (day 0) using California Verbal Learning Test-Third Edition (CVLT-3). Z scores with a mean of zero and a standard deviation of 1 are used. Higher scores mean better performance.
Impact of iron deficiency anemia on emotional health
Emotional health will be assessed by using NIH toolbox emotion battery at baseline. T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean higher number/frequency of symptoms.
Impact of iron therapy on emotional health in people with iron deficiency anemia.
Emotional health will be assessed at day 365 post iron therapy by using NIH toolbox emotion battery. T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean higher number/frequency of symptoms.
Impact of iron deficiency anemia on executive functions in day-to-day life.
Executive functions in day-to-day life will be assessed at baseline using the Behavior Rating Inventory of Executive Function 2 (BRIEF-2). T-scores with a mean of 50 and a standard deviation of 10 are used. Scores above T=65 may indicated problems.
Impact of iron therapy on executive functions in day-to-day life in people with iron deficiency anemia.
Executive functions in day-to-day life will be assessed at day 365 using the Behavior Rating Inventory of Executive Function 2 (BRIEF-2). T-scores with a mean of 50 and a standard deviation of 10 are used. Scores above T=65 may indicated problems.

Secondary Outcome Measures

Patient reported outcomes of health and quality of life will be assessed at baseline.
Rand Short Form Health Survey will be obtained at baseline. Score range is 0-100. Higher score means better quality of life.
Changes in patient reported outcomes of health and quality of life will be assessed over a period of 1 year post iron therapy.
Any effects and the changes in the effects of iron therapy will be assessed by obtaining the Rand Short Form Health Survey again post therapy at day 14 (for intravenous (IV) iron group only), day 90, day 180 and day 365 post iron therapy. Score range is 0-100. Higher score means better quality of life.
Patient reported outcomes of fatigue will be assessed at baseline.
Functional Assessment of Chronic Illness Therapy will be obtained at baseline. Score range is 0-52. Higher score means less fatigue.
Changes in patient reported outcomes of fatigue will be assessed over a period of 1 year post iron therapy.
Any effects and the changes in the effects of iron therapy will be assessed by obtaining the Functional Assessment of Chronic Illness Therapy again post therapy at day 14 (for intravenous (IV) iron group only), day 90, day 180 and day 365 post iron therapy. Score range is 0-52. Higher score means less fatigue.
Impact of iron deficiency anemia on MRI measured brain iron in deep brain nuclei, hippocampus, whole brain grey and white matter.
Quantitative susceptibility mapping will be assessed at baseline.
Changes in the impact of iron therapy on MRI measured brain iron in deep brain nuclei, hippocampus, whole brain grey and white matter.
Quantitative susceptibility mapping will be assessed at day 14 (for intravenous (IV) iron group only), day 90 and day 365 post iron therapy.
Changes in hemoglobin and ferritin will be assessed to determine durability of hemoglobin and ferritin response to therapy from baseline to 1 year post iron therapy.
Determine effect sizes of the durability of iron replacement over a period of one year following treatment with oral or intravenous iron.
Screening for Restless Legs Syndrome (RLS) at baseline
RLS will be assessed at baseline using the Henning Telephone Diagnostic Interview will be done at baseline. Scores are as follows: 0 = no symptoms; 1 = bedtime symptoms after or within an hour of going to bed; 2 = evening and bedtime symptoms starting at or after 6:00 pm; and 3 = day and night symptoms starting before 6:00 pm. Higher score indicates more severe RLS.
Changes in Restless Legs Syndrome (RLS) as an effect of iron therapy in people with iron deficiency anemia will be assessed post iron therapy.
Changes in RLS will be assessed by using John Hopkins Telephone Diagnostic Interview at time points over one year post iron therapy. Scores are as follows: 0 = no symptoms; 1 = bedtime symptoms after or within an hour of going to bed; 2 = evening and bedtime symptoms starting at or after 6:00 pm; and 3 = day and night symptoms starting before 6:00 pm. Higher score indicates more severe RLS.
Acute impact of intravenous (IV) iron therapy on visuospatial memory in people with iron deficiency anemia.
Visuospatial memory will be assessed at day 14 post IV iron using Brief Visuospatial Memory Test-Revised (BVMT-R). T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean better performance.
Acute impact of intravenous (IV) iron therapy on list learning and recall task in people with iron deficiency anemia.
List learning and recall task will be assessed at day 14 post IV iron using California Verbal Learning Test-Third Edition (CVLT-3) alternate form. Z scores with a mean of zero and a standard deviation of 1 are used. Higher scores mean better performance.

Full Information

First Posted
May 3, 2023
Last Updated
July 10, 2023
Sponsor
Children's Hospital Los Angeles
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1. Study Identification

Unique Protocol Identification Number
NCT05929729
Brief Title
Iron Deficiency Anemia
Acronym
IDA
Official Title
Neurovascular and Neurocognitive Consequences of Iron Deficiency Anemia
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 1, 2023 (Anticipated)
Primary Completion Date
September 1, 2028 (Anticipated)
Study Completion Date
September 1, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Hospital Los Angeles

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a trial with an observational and an interventional arm, in patients with moderate to severe anemia and control subjects. The main purposes of this study is to phenotype the scope of neurocognitive deficits from iron deficiency anemia (IDA) in adult women, determine derangements in cerebral perfusion, vascular reactivity, functional connectivity, and blood brain barrier permeability in adult-onset IDA and relate them to neurocognitive deficits, as well as determine the reversibility and durability of both the physiologic and neurocognitive derangements by iron replacement therapy. All eligible subjects will be asked to provide informed consent before participating in the study.
Detailed Description
This is a trial with an observational and an interventional arm, in patients with moderate to severe anemia and control subjects. The main purposes of this study is to phenotype the scope of neurocognitive deficits from iron deficiency anemia (IDA) in adult women, determine derangements in cerebral perfusion, vascular reactivity, functional connectivity, and blood brain barrier permeability in adult-onset IDA and relate them to neurocognitive deficits, as well as determine the reversibility and durability of both the physiologic and neurocognitive derangements by iron replacement therapy. All eligible subjects will be asked to provide informed consent before participating in the study. Comprehensive cerebrovascular magnetic resonance imaging (MRI), bloodwork, patient reported outcomes, and neurocognitive testing will be collected from all subjects in the observational arm. 136 subjects total will be enrolled, 40 controls and 96 anemic subjects. The 96 eligible anemic subjects will then be invited to enroll in the interventional arm of the study. Anticipating a drop-out rate of 20%, 40 will be randomized into intravenous iron therapy, and 40 will be randomized into standard of care (oral iron via primary care). Repeated tests will be done at different timepoints to assess the effects and durability of iron therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
IDA - Iron Deficiency Anemia, Anemia, Iron Deficiency Anemia, Anemia, Iron Deficiency

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
136 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intravenous (IV) iron
Arm Type
Experimental
Arm Description
This group will receive intravenous iron (ferric carboxymaltose), which consists of two doses of 15 mg/g given (max individual dose 750 mg) at least seven days apart. The drug is administered as an infusion over 30 minutes
Arm Title
Standard of care iron
Arm Type
Other
Arm Description
This group will be referred to their primary care provider for oral iron therapy. If a participant cannot obtain care from a physician, the hematology team will call in a prescription for oral ferrous sulfate, 325 mg, taken once a day for 12 weeks.
Arm Title
Healthy Controls
Arm Type
No Intervention
Arm Description
This group will only be participating in the observational part of the study and serve as our controls.
Intervention Type
Drug
Intervention Name(s)
Ferric carboxymaltose
Intervention Description
Refer to arm/group descriptions
Intervention Type
Drug
Intervention Name(s)
ferrous sulfate
Intervention Description
Refer to arm/group descriptions
Primary Outcome Measure Information:
Title
Impact of iron deficiency anemia on regional cerebrovascular oxygen delivery (ml O2/100g/min).
Description
Baseline impact of iron deficiency anemia on cerebrovascular oxygen delivery will be assessed by measuring cerebral blood flow and oxygen content through MRI (time-encoded arterial spin labelling) and peripheral blood sample
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on regional cerebrovascular oxygen delivery (ml O2/100g/min) in iron deficiency anemia at day 90 post therapy
Description
Impact of iron therapy on cerebrovascular oxygen delivery will be assessed at day 90 by measuring cerebral blood flow and oxygen content through MRI (time-encoded arterial spin labelling) and peripheral blood sample in people with iron deficiency anemia.
Time Frame
Day 90 post-iron-therapy
Title
Impact of iron therapy on regional cerebrovascular oxygen delivery (ml O2/100g/min) in iron deficiency anemia at day 365 post therapy.
Description
Impact of iron therapy on cerebrovascular oxygen delivery will be assessed at day 365 by measuring cerebral blood flow and oxygen content through MRI (time-encoded arterial spin labelling) and peripheral blood sample in people with iron deficiency anemia
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on cerebrovascular flow reactivity (%SI change/%ETCO2)
Description
baseline MRI with blood oxygenation level dependent (BOLD) acquisition will be assessed in response to carbon dioxide exposure to determine whether iron deficiency anemia affects cerebrovascular reserve
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on cerebrovascular flow reactivity (%SI change/%ETCO2) in people with iron deficiency anemia at 90 days post iron therapy.
Description
Impact of iron therapy on cardiovascular reserve in iron deficiency anemia will be assessed using MRI with blood oxygenation level dependent (BOLD) acquisition at 90 days post iron therapy.
Time Frame
Day 90 post iron therapy
Title
Impact of iron therapy on cerebrovascular flow reactivity (%SI change/%ETCO2) in people with iron deficiency anemia at day 365.
Description
Impact of iron therapy on cardiovascular reserve in iron deficiency anemia will be assessed using MRI with blood oxygenation level dependent (BOLD) acquisition at day 365 post iron therapy.
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on blood brain barrier permeability surface area product (ml H20/100g/min)
Description
baseline PSA product using water-extraction-with phase- contrast-arterial-spin-tagging (WEPCAST) MRI will be assessed to determine whether iron deficiency anemia affects blood brain barrier permeability to water
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on blood brain barrier permeability surface area product (ml H20/100g/min) in iron deficiency anemia will be assessed at 90 days.
Description
PSA product using water-extraction-with phase- contrast-arterial-spin-tagging (WEPCAST) MRI will be assessed at 90 days post iron therapy to determine the impact of iron therapy on blood brain barrier permeability to water in patients with iron deficiency anemia.
Time Frame
Day 90 post iron therapy
Title
Impact of iron therapy on blood brain barrier permeability surface area product (ml H20/100g/min) in iron deficiency anemia will be assessed again at day 365.
Description
PSA product using water-extraction-with phase- contrast-arterial-spin-tagging (WEPCAST) MRI will be assessed at 365 days post iron therapy to determine the impact of iron therapy on blood brain barrier permeability to water in patients with iron deficiency anemia.
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on cerebral metabolic rate of oxygen (ml O2/100g/min).
Description
Baseline T2 relaxation under spin tagging (TRUST) acquisition via MRI will be used to assess any impact of iron deficiency anemia on cerebral metabolic rate of oxygen
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on cerebral metabolic rate of oxygen (ml O2/100g/min) in people with iron deficiency anemia at day 90 post iron therapy.
Description
T2 relaxation under spin tagging (TRUST) acquisition via MRI will be used to assess any impact of iron therapy on cerebral metabolic rate of oxygen in anemic subjects at day 90.
Time Frame
Day 90 post iron therapy
Title
Impact of iron therapy on cerebral metabolic rate of oxygen (ml O2/100g/min) in people with iron deficiency anemia at day 365 post iron therapy.
Description
T2 relaxation under spin tagging (TRUST) acquisition via MRI will be used to assess any impact of iron therapy on cerebral metabolic rate of oxygen in anemic subjects at day 365.
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on total brain blood flow (ml blood/100g/min).
Description
Phase contrast MRI will be assessed to determine whether iron deficiency anemia affects total brain blood flow at baseline
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on total brain blood flow (ml blood/100g/min) in people with iron deficiency anemia at day 90
Description
Phase contrast MRI will be assessed at day 90 post iron therapy to determine whether iron therapy affects total brain blood flow in subjects with iron deficiency anemia
Time Frame
Day 90 post iron therapy
Title
Impact of iron therapy on total brain blood flow (ml blood/100g/min) in people with iron deficiency anemia at day 365
Description
Phase contrast MRI will be assessed at day 365 post iron therapy to determine whether iron therapy affects total brain blood flow in subjects with iron deficiency anemia
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on visual-motor integration.
Description
Visual-motor integration at baseline (day 0) will be assessed using Beery Buktenica Developmental Test of Visual-Motor Integration (6th Edition). Standardized scores with a mean of 100 and a standard deviation of 15 are used. Higher scores mean better performance.
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on visual-motor integration in people with iron deficiency anemia.
Description
Visual-motor integration will be assessed using Beery Buktenica Developmental Test of Visual-Motor Integration (6th Edition) at day 365 post iron-therapy. Standardized scores with a mean of 100 and a standard deviation of 15 are used. Higher scores mean better performance.
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on sustained attention.
Description
Sustained attention at baseline (day 0) will be assessed using Conners' Continuous Performance Test (3rd Edition) at day 90 post iron-therapy. T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean worse performance.
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on sustained attention in people with iron deficiency anemia.
Description
Sustained attention will be assessed using Conners' Continuous Performance Test (3rd Edition) at day 365 post iron-therapy. T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean worse performance.
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on working memory function.
Description
Working memory function at baseline (day 0) will be assessed using Digit Span, Coding, and Symbol Search Subtests from Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV). Scaled scores with a mean of 10 and a standard deviation of 3 are used. Higher scores mean better performance.
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on working memory function in people with iron deficiency anemia.
Description
Working memory function will be assessed at day 365 post iron therapy using Digit Span, Coding, and Symbol Search Subtests from Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV). Scaled scores with a mean of 10 and a standard deviation of 3 are used. Higher scores mean better performance.
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on the ability to inhibit cognitive interference
Description
The ability to inhibit cognitive interference at baseline (day 0) will be assessed using Color-Word Interference Subtest from the Delis-Kaplan Executive Function System (D-KEFS). Scaled scores with a mean of 10 and a standard deviation of 3 are used. Higher scores mean better performance.
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on the ability to inhibit cognitive interference in people with iron deficiency anemia.
Description
The ability to inhibit cognitive interference at day 365 post iron therapy will be assessed using Color-Word Interference Subtest from the Delis-Kaplan Executive Function System (D-KEFS). Scaled scores with a mean of 10 and a standard deviation of 3 are used. Higher scores mean better performance.
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on fine motor control.
Description
Fine motor control will be assessed at baseline (day 0) using Reitan Finger Tapping. Z scores with a mean of zero and a standard deviation of one are used. Higher scores mean better performance.
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on fine motor control in people with iron deficiency anemia.
Description
Fine motor control will be assessed at day 365 post iron therapy using Reitan Finger Tapping. Z scores with a mean of zero and a standard deviation of one are used. Higher scores mean better performance.
Time Frame
Day 365 post iron therapy
Title
Impact of iron therapy on list learning and recall task in people with iron deficiency anemia.
Description
List learning and recall task will be assessed at day 365 post iron therapy using California Verbal Learning Test-Third Edition (CVLT-3). Z scores with a mean of zero and a standard deviation of 1 are used. Higher scores mean better performance.
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on visuospatial memory
Description
Visuospatial memory will be assessed at baseline (day 0) using Brief Visuospatial Memory Test-Revised (BVMT-R). T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean better performance.
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on visuospatial memory in people with iron deficiency anemia.
Description
Visuospatial memory will be assessed at day 365 post iron therapy using Brief Visuospatial Memory Test-Revised (BVMT-R). T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean better performance.
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on general intellectual functioning, verbal and nonverbal abilities.
Description
General intellectual functioning, verbal and nonverbal abilities will be assessed at baseline (day 0) using Wechsler Abbreviated Scale of Intelligence-Second Edition (WASI-2). T scores with a mean of 50 and a standard deviation of 10 are used for the subtests, with standard scores (mean of 100 and standard deviation of 15) used for composite scores. Higher scores mean better performance.
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on general intellectual functioning, verbal and nonverbal abilities in people with iron deficiency anemia.
Description
General intellectual functioning, verbal and nonverbal abilities will be assessed at day 365 post iron therapy using Wechsler Abbreviated Scale of Intelligence-Second Edition (WASI-2). T scores with a mean of 50 and a standard deviation of 10 are used for the subtests, with standard scores (mean of 100 and standard deviation of 15) used for composite scores. Higher scores mean better performance.
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on cognitive flexibility and processing speed.
Description
Cognitive flexibility and processing speed will be assessed at baseline (day 0) using NIH Toolbox: Dimensional Change Card Sort and Pattern Comparison Processing Speed. Standard scores with a mean of 100 and a standard deviation of 15 are used. Higher scores mean better performance.
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on cognitive flexibility and processing speed in people with iron deficiency anemia.
Description
Cognitive flexibility and processing speed will be assessed at day 365 post iron therapy using NIH Toolbox: Dimensional Change Card Sort and Pattern Comparison Processing Speed. Standard scores with a mean of 100 and a standard deviation of 15 are used. Higher scores mean better performance.
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on list learning and recall task
Description
List learning and recall task will be assessed at baseline (day 0) using California Verbal Learning Test-Third Edition (CVLT-3). Z scores with a mean of zero and a standard deviation of 1 are used. Higher scores mean better performance.
Time Frame
Day 0 (observation arm)
Title
Impact of iron deficiency anemia on emotional health
Description
Emotional health will be assessed by using NIH toolbox emotion battery at baseline. T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean higher number/frequency of symptoms.
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on emotional health in people with iron deficiency anemia.
Description
Emotional health will be assessed at day 365 post iron therapy by using NIH toolbox emotion battery. T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean higher number/frequency of symptoms.
Time Frame
Day 365 post iron therapy
Title
Impact of iron deficiency anemia on executive functions in day-to-day life.
Description
Executive functions in day-to-day life will be assessed at baseline using the Behavior Rating Inventory of Executive Function 2 (BRIEF-2). T-scores with a mean of 50 and a standard deviation of 10 are used. Scores above T=65 may indicated problems.
Time Frame
Day 0 (observation arm)
Title
Impact of iron therapy on executive functions in day-to-day life in people with iron deficiency anemia.
Description
Executive functions in day-to-day life will be assessed at day 365 using the Behavior Rating Inventory of Executive Function 2 (BRIEF-2). T-scores with a mean of 50 and a standard deviation of 10 are used. Scores above T=65 may indicated problems.
Time Frame
Day 365 post iron therapy
Secondary Outcome Measure Information:
Title
Patient reported outcomes of health and quality of life will be assessed at baseline.
Description
Rand Short Form Health Survey will be obtained at baseline. Score range is 0-100. Higher score means better quality of life.
Time Frame
Day 0 (observation arm)
Title
Changes in patient reported outcomes of health and quality of life will be assessed over a period of 1 year post iron therapy.
Description
Any effects and the changes in the effects of iron therapy will be assessed by obtaining the Rand Short Form Health Survey again post therapy at day 14 (for intravenous (IV) iron group only), day 90, day 180 and day 365 post iron therapy. Score range is 0-100. Higher score means better quality of life.
Time Frame
Day 14 (for IV iron group only), Day 90, Day 180, Day 365
Title
Patient reported outcomes of fatigue will be assessed at baseline.
Description
Functional Assessment of Chronic Illness Therapy will be obtained at baseline. Score range is 0-52. Higher score means less fatigue.
Time Frame
Day 0 (observation arm)
Title
Changes in patient reported outcomes of fatigue will be assessed over a period of 1 year post iron therapy.
Description
Any effects and the changes in the effects of iron therapy will be assessed by obtaining the Functional Assessment of Chronic Illness Therapy again post therapy at day 14 (for intravenous (IV) iron group only), day 90, day 180 and day 365 post iron therapy. Score range is 0-52. Higher score means less fatigue.
Time Frame
Day 14 (for IV iron group only), Day 90, Day 180, Day 365
Title
Impact of iron deficiency anemia on MRI measured brain iron in deep brain nuclei, hippocampus, whole brain grey and white matter.
Description
Quantitative susceptibility mapping will be assessed at baseline.
Time Frame
Day 0 (observation arm)
Title
Changes in the impact of iron therapy on MRI measured brain iron in deep brain nuclei, hippocampus, whole brain grey and white matter.
Description
Quantitative susceptibility mapping will be assessed at day 14 (for intravenous (IV) iron group only), day 90 and day 365 post iron therapy.
Time Frame
Day 14 (for IV iron group only), Day 90, Day 365
Title
Changes in hemoglobin and ferritin will be assessed to determine durability of hemoglobin and ferritin response to therapy from baseline to 1 year post iron therapy.
Description
Determine effect sizes of the durability of iron replacement over a period of one year following treatment with oral or intravenous iron.
Time Frame
Day 0 (observation arm), Day 14 (for IV iron treated), Day 90, Day 180, Day 365
Title
Screening for Restless Legs Syndrome (RLS) at baseline
Description
RLS will be assessed at baseline using the Henning Telephone Diagnostic Interview will be done at baseline. Scores are as follows: 0 = no symptoms; 1 = bedtime symptoms after or within an hour of going to bed; 2 = evening and bedtime symptoms starting at or after 6:00 pm; and 3 = day and night symptoms starting before 6:00 pm. Higher score indicates more severe RLS.
Time Frame
Day 0 (observation arm)
Title
Changes in Restless Legs Syndrome (RLS) as an effect of iron therapy in people with iron deficiency anemia will be assessed post iron therapy.
Description
Changes in RLS will be assessed by using John Hopkins Telephone Diagnostic Interview at time points over one year post iron therapy. Scores are as follows: 0 = no symptoms; 1 = bedtime symptoms after or within an hour of going to bed; 2 = evening and bedtime symptoms starting at or after 6:00 pm; and 3 = day and night symptoms starting before 6:00 pm. Higher score indicates more severe RLS.
Time Frame
Day 14 (for intravenous iron group only), Day, 90, Day 180, Day 365
Title
Acute impact of intravenous (IV) iron therapy on visuospatial memory in people with iron deficiency anemia.
Description
Visuospatial memory will be assessed at day 14 post IV iron using Brief Visuospatial Memory Test-Revised (BVMT-R). T-scores with a mean of 50 and a standard deviation of 10 are used. Higher scores mean better performance.
Time Frame
Day 14 post IV iron therapy
Title
Acute impact of intravenous (IV) iron therapy on list learning and recall task in people with iron deficiency anemia.
Description
List learning and recall task will be assessed at day 14 post IV iron using California Verbal Learning Test-Third Edition (CVLT-3) alternate form. Z scores with a mean of zero and a standard deviation of 1 are used. Higher scores mean better performance.
Time Frame
Day 14 post IV iron therapy

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Observational arm: Age between 16 and 60 years of age. Any ethnicity. Female Anemic group: hemoglobin ≤10.5 g/dl or hematocrit <32% from finger prick or plethysmography test, or <11 g/dl from venipuncture blood draw Control group: hemoglobin >13.2 g/dl or hematocrit >39.6% Interventional arm: Criteria for observational component, plus Iron deficiency anemia based upon attending hematologist interpretation of transferrin saturation, ferritin, and other ancillary labs including hs-CRP, MMA, hemoglobin electrophoresis Exclusion Criteria: Observational arm: Diabetes requiring medication. Hypertension requiring medication. Sleep disordered breathing requiring intervention. Body mass index >40 (morbid obesity) Contraindications to MRI, including pacemaker, severe claustrophobia, pregnancy. Known systemic inflammatory disease such as inflammatory bowel disease, systemic lupus erythematosus, or scleroderma. Known HIV. Interventional arm: Criteria for observational component, plus Prior reaction to intravenous iron. History of multiple drug allergies. History of severe asthma, eczema, or atopy. Systemic mastocytosis. Severe respiratory or cardiac disease.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Silvie Suriany, MSc
Phone
323-361-4783
Email
ssuriany@chla.usc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Wood, MD, PhD
Organizational Affiliation
Children's Hospital Los Angeles
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Blood Donor Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Silvie Suriany, MSc
Phone
323-361-4783
Email
ssuriany@chla.usc.edu
First Name & Middle Initial & Last Name & Degree
Lefan Zhuang, MD
Email
lzhuang@coh.org
Facility Name
Cedar Sinai Blood Bank
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027-6062
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Silvie Suriany, MSc
Phone
323-361-4783
Email
ssuriany@chla.usc.edu
First Name & Middle Initial & Last Name & Degree
Ellen Klapper, MD
Email
Ellen.Klapper@cshs.org
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Silvie Suriany, MSc
Phone
323-361-4783
Email
ssuriany@chla.usc.edu
First Name & Middle Initial & Last Name & Degree
John Wood, MD,PhD
Facility Name
University of California, Los Angeles Blood Donor Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Silvie Suriany, MSc
Phone
323-361-4783
Email
ssuriany@chla.usc.edu
First Name & Middle Initial & Last Name & Degree
Dawn Ward, MD
Email
DWard@mednet.ucla.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Iron Deficiency Anemia

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