Iron Deficiency Anemia (IDA) and the Brain

Официальное название

Neurovascular and Neurocognitive Consequences of Iron Deficiency Anemia

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Ferric derisomaltose
  Refer to arm/group descriptions
• Препарат NovaFerrum
  Refer to arm/group descriptions

Первичные конечные точки

• Impact of iron deficiency anemia on regional cerebrovascular oxygen delivery (ml O2/100g/min). [Срок оценки: Day 0 (observation arm)]
• Impact of iron therapy on regional cerebrovascular oxygen delivery (ml O2/100g/min) in iron deficiency anemia at day 90 post therapy [Срок оценки: Day 90 post-iron-therapy]
• Impact of iron therapy on regional cerebrovascular oxygen delivery (ml O2/100g/min) in iron deficiency anemia at day 365 post therapy. [Срок оценки: Day 365 post iron therapy]
• Impact of iron deficiency anemia on cerebrovascular flow reactivity (%SI change/%ETCO2) [Срок оценки: Day 0 (observation arm)]
• Impact of iron therapy on cerebrovascular flow reactivity (%SI change/%ETCO2) in people with iron deficiency anemia at 90 days post iron therapy. [Срок оценки: Day 90 post iron therapy]
• Impact of iron therapy on cerebrovascular flow reactivity (%SI change/%ETCO2) in people with iron deficiency anemia at day 365. [Срок оценки: Day 365 post iron therapy]
• Impact of iron deficiency anemia on blood brain barrier permeability surface area product (ml H20/100g/min) [Срок оценки: Day 0 (observation arm)]
• 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. [Срок оценки: Day 90 post iron therapy]
• 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. [Срок оценки: Day 365 post iron therapy]
• Impact of iron deficiency anemia on cerebral metabolic rate of oxygen (ml O2/100g/min). [Срок оценки: Day 0 (observation arm)]

Вторичные конечные точки (11)

• Patient reported outcomes of health and quality of life will be assessed at baseline. [Срок оценки: Day 0 (observation arm)]
• Changes in patient reported outcomes of health and quality of life will be assessed over a period of 1 year post iron therapy. [Срок оценки: Day 14 (for IV iron group only), Day 90, Day 180, Day 365]
• Patient reported outcomes of fatigue will be assessed at baseline. [Срок оценки: Day 0 (observation arm)]
• Changes in patient reported outcomes of fatigue will be assessed over a period of 1 year post iron therapy. [Срок оценки: Day 14 (for IV iron group only), Day 90, Day 180, Day 365]
• Impact of iron deficiency anemia on MRI measured brain iron in deep brain nuclei, hippocampus, whole brain grey and white matter. [Срок оценки: Day 0 (observation arm)]
• Changes in the impact of iron therapy on MRI measured brain iron in deep brain nuclei, hippocampus, whole brain grey and white matter. [Срок оценки: Day 14 (for IV iron group only), Day 90, Day 365]
• 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. [Срок оценки: Day 0 (observation arm), Day 14 (for IV iron treated), Day 90, Day 180, Day 365]
• Screening for Restless Legs Syndrome (RLS) at baseline [Срок оценки: Day 0 (observation arm)]
• Changes in Restless Legs Syndrome (RLS) as an effect of iron therapy in people with iron deficiency anemia will be assessed post iron therapy. [Срок оценки: Day 14 (for intravenous iron group only), Day, 90, Day 180, Day 365]
• Acute impact of intravenous (IV) iron therapy on visuospatial memory in people with iron deficiency anemia. [Срок оценки: Day 14 post IV iron therapy]
• Acute impact of intravenous (IV) iron therapy on list learning and recall task in people with iron deficiency anemia. [Срок оценки: Day 14 post IV iron therapy]

Критерии участия

Критерии включения

• 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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

США · 4 центра

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

Идентификаторы

NCT: NCT05929729 · CHLA-23-00173 · 1R01NS117430-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗