Iron Deficiency Anemia (IDA)

Anemia Clinical Trial

— IDA  

Official title:

Neurovascular and Neurocognitive Consequences of Iron Deficiency Anemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05929729
• Other study ID #: CHLA-23-00173
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: December 1, 2023
• Est. completion date: September 1, 2028

Study information

• Verified date: November 2023
• Source: Children's Hospital Los Angeles
• Contact: Silvie Suriany, MSc
• Phone: 323-361-4783
• Email: ssuriany[@]chla.usc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 136
• Est. completion date: September 1, 2028
• Est. primary completion date: September 1, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Observational arm:

1. Age between 18 and 60 years of age.

2. Any ethnicity.

3. Female

4. Anemic group: hemoglobin =10.5 g/dl or hematocrit <32% from finger prick or plethysmography test, or <11 g/dl from venipuncture blood draw

5. Control group: hemoglobin >13.2 g/dl or hematocrit >39.6%

• Interventional arm:

1. Criteria for observational component, plus

2. 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:

1. Diabetes requiring medication.

2. Hypertension requiring medication.

3. Sleep disordered breathing requiring intervention.

4. Body mass index >40 (morbid obesity)

5. Contraindications to MRI, including pacemaker, severe claustrophobia, pregnancy.

6. Known systemic inflammatory disease such as inflammatory bowel disease, systemic lupus erythematosus, or scleroderma.

7. Known HIV.

• Interventional arm:

1. Criteria for observational component, plus

2. Prior reaction to intravenous iron.

3. History of multiple drug allergies.

4. History of severe asthma, eczema, or atopy.

5. Systemic mastocytosis.

6. Severe respiratory or cardiac disease.

7. Having no access to a physician who can manage the iron deficiency anemia.

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron Deficiency
• Anemia, Iron-Deficiency
• Deficiency Diseases
• Iron Deficiency Anemia

Intervention

Drug:
• Ferric derisomaltose
Refer to arm/group descriptions
• NovaFerrum
Refer to arm/group descriptions

Locations

Country	Name	City	State
United States	City of Hope Blood Donor Center	Duarte	California
United States	Cedar Sinai Blood Bank	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	University of California, Los Angeles Blood Donor Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Los Angeles

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Day 0 (observation arm)
Primary	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.	Day 90 post-iron-therapy
Primary	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	Day 365 post iron therapy
Primary	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	Day 0 (observation arm)
Primary	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.	Day 90 post iron therapy
Primary	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.	Day 365 post iron therapy
Primary	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	Day 0 (observation arm)
Primary	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.	Day 90 post iron therapy
Primary	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.	Day 365 post iron therapy
Primary	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	Day 0 (observation arm)
Primary	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.	Day 90 post iron therapy
Primary	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.	Day 365 post iron therapy
Primary	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	Day 0 (observation arm)
Primary	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	Day 90 post iron therapy
Primary	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	Day 365 post iron therapy
Primary	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.	Day 0 (observation arm)
Primary	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.	Day 365 post iron therapy
Primary	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.	Day 0 (observation arm)
Primary	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.	Day 365 post iron therapy
Primary	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.	Day 0 (observation arm)
Primary	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.	Day 365 post iron therapy
Primary	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.	Day 0 (observation arm)
Primary	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.	Day 365 post iron therapy
Primary	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.	Day 0 (observation arm)
Primary	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.	Day 365 post iron therapy
Primary	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.	Day 365 post iron therapy
Primary	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.	Day 0 (observation arm)
Primary	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.	Day 365 post iron therapy
Primary	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.	Day 0 (observation arm)
Primary	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.	Day 365 post iron therapy
Primary	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.	Day 0 (observation arm)
Primary	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.	Day 365 post iron therapy
Primary	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.	Day 0 (observation arm)
Primary	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.	Day 0 (observation arm)
Primary	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.	Day 365 post iron therapy
Primary	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.	Day 0 (observation arm)
Primary	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.	Day 365 post iron therapy
Secondary	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.	Day 0 (observation arm)
Secondary	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.	Day 14 (for IV iron group only), Day 90, Day 180, Day 365
Secondary	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.	Day 0 (observation arm)
Secondary	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.	Day 14 (for IV iron group only), Day 90, Day 180, Day 365
Secondary	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.	Day 0 (observation arm)
Secondary	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.	Day 14 (for IV iron group only), Day 90, Day 365
Secondary	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.	Day 0 (observation arm), Day 14 (for IV iron treated), Day 90, Day 180, Day 365
Secondary	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.	Day 0 (observation arm)
Secondary	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.	Day 14 (for intravenous iron group only), Day, 90, Day 180, Day 365
Secondary	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.	Day 14 post IV iron therapy
Secondary	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.	Day 14 post IV iron therapy