Clinical trial NCT05929729: Iron Deficiency Anemia (IDA) and the Brain
Official title: Neurovascular and Neurocognitive Consequences of Iron Deficiency Anemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: IDA - Iron Deficiency Anemia
Anemia
Iron Deficiency Anemia
Anemia, Iron Deficiency
Lead sponsor: Children's Hospital Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2023-07-03
Enrollment: 120
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

* Observational arm:

  1. Age between 16 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.

Primary outcomes:
measure: Impact of iron deficiency anemia on regional cerebrovascular oxygen delivery (ml O2/100g/min).
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on regional cerebrovascular oxygen delivery (ml O2/100g/min) in iron deficiency anemia at day 90 post therapy
timeFrame: Day 90 post-iron-therapy
measure: Impact of iron therapy on regional cerebrovascular oxygen delivery (ml O2/100g/min) in iron deficiency anemia at day 365 post therapy.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on cerebrovascular flow reactivity (%SI change/%ETCO2)
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on cerebrovascular flow reactivity (%SI change/%ETCO2) in people with iron deficiency anemia at 90 days post iron therapy.
timeFrame: Day 90 post iron therapy
measure: Impact of iron therapy on cerebrovascular flow reactivity (%SI change/%ETCO2) in people with iron deficiency anemia at day 365.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on blood brain barrier permeability surface area product (ml H20/100g/min)
timeFrame: Day 0 (observation arm)
measure: 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.
timeFrame: Day 90 post iron therapy
measure: 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.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on cerebral metabolic rate of oxygen (ml O2/100g/min).
timeFrame: Day 0 (observation arm)
measure: 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.
timeFrame: Day 90 post iron therapy
measure: 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.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on total brain blood flow (ml blood/100g/min).
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on total brain blood flow (ml blood/100g/min) in people with iron deficiency anemia at day 90
timeFrame: Day 90 post iron therapy
measure: Impact of iron therapy on total brain blood flow (ml blood/100g/min) in people with iron deficiency anemia at day 365
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on visual-motor integration.
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on visual-motor integration in people with iron deficiency anemia.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on sustained attention.
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on sustained attention in people with iron deficiency anemia.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on working memory function.
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on working memory function in people with iron deficiency anemia.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on the ability to inhibit cognitive interference
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on the ability to inhibit cognitive interference in people with iron deficiency anemia.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on fine motor control.
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on fine motor control in people with iron deficiency anemia.
timeFrame: Day 365 post iron therapy
measure: Impact of iron therapy on list learning and recall task in people with iron deficiency anemia.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on visuospatial memory
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on visuospatial memory in people with iron deficiency anemia.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on general intellectual functioning, verbal and nonverbal abilities.
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on general intellectual functioning, verbal and nonverbal abilities in people with iron deficiency anemia.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on cognitive flexibility and processing speed.
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on cognitive flexibility and processing speed in people with iron deficiency anemia.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on list learning and recall task
timeFrame: Day 0 (observation arm)
measure: Impact of iron deficiency anemia on emotional health
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on emotional health in people with iron deficiency anemia.
timeFrame: Day 365 post iron therapy
measure: Impact of iron deficiency anemia on executive functions in day-to-day life.
timeFrame: Day 0 (observation arm)
measure: Impact of iron therapy on executive functions in day-to-day life in people with iron deficiency anemia.
timeFrame: Day 365 post iron therapy
Secondary outcomes:
measure: Patient reported outcomes of health and quality of life will be assessed at baseline.
timeFrame: Day 0 (observation arm)
measure: Changes in patient reported outcomes of health and quality of life will be assessed over a period of 1 year post iron therapy.
timeFrame: Day 14 (for IV iron group only), Day 90, Day 180, Day 365
measure: Patient reported outcomes of fatigue will be assessed at baseline.
timeFrame: Day 0 (observation arm)
measure: Changes in patient reported outcomes of fatigue will be assessed over a period of 1 year post iron therapy.
timeFrame: Day 14 (for IV iron group only), Day 90, Day 180, Day 365
measure: Impact of iron deficiency anemia on MRI measured brain iron in deep brain nuclei, hippocampus, whole brain grey and white matter.
timeFrame: Day 0 (observation arm)
measure: Changes in the impact of iron therapy on MRI measured brain iron in deep brain nuclei, hippocampus, whole brain grey and white matter.
timeFrame: Day 14 (for IV iron group only), Day 90, Day 365
measure: 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.
timeFrame: Day 0 (observation arm), Day 14 (for IV iron treated), Day 90, Day 180, Day 365
measure: Screening for Restless Legs Syndrome (RLS) at baseline
timeFrame: Day 0 (observation arm)
measure: Changes in Restless Legs Syndrome (RLS) as an effect of iron therapy in people with iron deficiency anemia will be assessed post iron therapy.
timeFrame: Day 14 (for intravenous iron group only), Day, 90, Day 180, Day 365
measure: Acute impact of intravenous (IV) iron therapy on visuospatial memory in people with iron deficiency anemia.
timeFrame: Day 14 post IV iron therapy
measure: Acute impact of intravenous (IV) iron therapy on list learning and recall task in people with iron deficiency anemia.
timeFrame: Day 14 post IV iron therapy
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Blood Donor Center
state: California
city: Los Angeles
country: United States
facility: Cedar Sinai Blood Bank
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles Blood Donor Center
state: California
Study officials:
affiliation: Children's Hospital Los Angeles
name: John Wood, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: