Neuroimaging Ancillary Study

Sponsor

Thomas Jefferson University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05545527

Collaborator

Jawaharlal Nehru Medical College (Other)

200

Enrollment

Location

28.1

Anticipated Duration (Months)

7.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

As a follow-up to the RAPIDIRON Trial (NCT05358509), and in combination with the RAPIDIRON-KIDS Study (NCT05504863), this study will involve infants of RAPIDIRON Trial participants recruited at one site in Karnataka and is designed to implement a magnetic resonance imaging (MRI) protocol and incorporate neuroimaging measures. Implementation of this study will promote an understanding of the effects on fetal and neonatal brain development, including iron deposition in brain tissues, when a woman is treated for iron deficiency anemia (IDA) by either (a) providing her oral iron tablets and instructions for use; or (b) administering a single-dose IV iron infusion for the treatment of IDA during pregnancy.

Condition or Disease	Intervention/Treatment	Phase
Iron Deficiency Anemia Iron Deficiency Anemia of Pregnancy Neurodevelopmental Disorder of Foetus Iron Deficiency Anemia Treatment Fetal Neurodevelopmental Disorder Child Development	Drug: Ferric carboxymaltose Drug: Iron isomaltoside Drug: Ferric Sulfate

Detailed Description

The hypothesis of this study is as follows:

Reduced iron availability through fetal development impacts fundamental early neurodevelopmental processes, including neurogenesis of the hippocampus, amygdala, and other 'core' deep brain basal ganglia regions (e.g., globus pallidus); and myelination of the brain's white matter connecting these deep brain structures and higher-order cortical regions involved in motor, memory, and executive functioning.

The specific aims of this Neuroimaging Ancillary Study are:

To determine impact of the IV iron intervention compared to oral iron on specific markers of brain development; and
As a secondary analysis, to explore whether infant sex acts as a moderator of treatment on these specific brain development markers.

This study will recruit pregnant mothers currently participating in the parent RAPIDIRON Trial, who will be approached to give consent for themselves and their offspring for participation in this Neuroimaging Ancillary Study. Participation in this Ancillary Study will involve assessments at 32-35 weeks fetal gestational age, birth, 4 months, 12 months, and 24 months post-delivery. This will involve a fetal MRI and three post-birth MRIs conducted with the offspring to collect the main neuroimaging measures. In addition, we will collect various secondary offspring and maternal measures including child auditory brain response; maternal depression, anxiety, perceived stress, and empowerment; hair cortisol; and breastmilk micronutrient analysis.

Please see the protocol for additional details.

Study Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Neuroimaging Ancillary Study of the IV Iron RAPIDIRON Trial

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
RAPIDIRON IV iron intervention arm 1 Maternal participants in this arm were given a single dose of an IV iron formulation - ferric carboxymaltose - during pregnancy as part of their participation in the parent RAPIDIRON Trial. Participants weighing 50kg and over received a single dose having 1000mg of iron, with others receiving a lower dose as determined by a formula used by the manufacturer (20mg iron/kg body weight). This was given between 14 and 17 weeks fetal gestational age.	Drug: Ferric carboxymaltose As part of the RAPIDIRON Trial, maternal participants randomized to intervention arm 1 were given a single dose of ferric carboxymaltose between 14 and 17 weeks of pregnancy.
RAPIDIRON IV iron intervention arm 2 Maternal participants in this arm were given a single dose of an IV iron formulation - iron isomaltoside - during pregnancy as part of their participation in the parent RAPIDIRON Trial. Participants weighing 50kg and over received a single dose having 1000mg of iron, with others receiving a lower dose as determined by a formula used by the manufacturer (20mg iron/kg body weight). This was given between 14 and 17 weeks fetal gestational age.	Drug: Iron isomaltoside As part of the RAPIDIRON Trial, maternal participants randomized to intervention arm 2 were given a single dose of iron isomaltoside between 14 and 17 weeks of pregnancy. Other Names: Ferric derisomaltose
RAPIDIRON active comparator arm Maternal participants in this arm of the RAPIDIRON Trial were given ferrous sulfate tablets with 60mg elemental iron each and instructed to take two per day (one in the morning and one at night) throughout their pregnancy.	Drug: Ferric Sulfate As part of the RAPIDIRON Trial, maternal participants randomized to the active comparator arm were given 200 ferrous sulfate tablets immediately after randomization (~12 weeks of pregnancy). Participants were instructed to take two tablets a day, with each tablet containing 60mg elemental iron. Other Names: Ferric sulphate

Arm

Intervention/Treatment

RAPIDIRON IV iron intervention arm 1

Maternal participants in this arm were given a single dose of an IV iron formulation - ferric carboxymaltose - during pregnancy as part of their participation in the parent RAPIDIRON Trial. Participants weighing 50kg and over received a single dose having 1000mg of iron, with others receiving a lower dose as determined by a formula used by the manufacturer (20mg iron/kg body weight). This was given between 14 and 17 weeks fetal gestational age.

Drug: Ferric carboxymaltose

As part of the RAPIDIRON Trial, maternal participants randomized to intervention arm 1 were given a single dose of ferric carboxymaltose between 14 and 17 weeks of pregnancy.

RAPIDIRON IV iron intervention arm 2

Maternal participants in this arm were given a single dose of an IV iron formulation - iron isomaltoside - during pregnancy as part of their participation in the parent RAPIDIRON Trial. Participants weighing 50kg and over received a single dose having 1000mg of iron, with others receiving a lower dose as determined by a formula used by the manufacturer (20mg iron/kg body weight). This was given between 14 and 17 weeks fetal gestational age.

Drug: Iron isomaltoside

As part of the RAPIDIRON Trial, maternal participants randomized to intervention arm 2 were given a single dose of iron isomaltoside between 14 and 17 weeks of pregnancy.

Other Names:

Ferric derisomaltose

RAPIDIRON active comparator arm

Maternal participants in this arm of the RAPIDIRON Trial were given ferrous sulfate tablets with 60mg elemental iron each and instructed to take two per day (one in the morning and one at night) throughout their pregnancy.

Drug: Ferric Sulfate

As part of the RAPIDIRON Trial, maternal participants randomized to the active comparator arm were given 200 ferrous sulfate tablets immediately after randomization (~12 weeks of pregnancy). Participants were instructed to take two tablets a day, with each tablet containing 60mg elemental iron.

Other Names:

Ferric sulphate

Outcome Measures

Primary Outcome Measures

Fetal hippocampal volume [32-35 weeks fetal gestational age]
Fetal hippocampus volume, measured via fetal MRI
Fetal diffusion parameters: fractional anisotropy (FA) [32-35 weeks fetal gestational age]
Fetal white matter microstructure will be measured via FA at the posterior limb of internal capsule using fetal MRI
Fetal diffusion parameters: mean diffusivity [32-35 weeks fetal gestational age]
Fetal white matter microstructure will be measured via MD at the posterior limb of internal capsule using fetal MRI

Secondary Outcome Measures

Fetal sub-cortical gray matter structures [32-35 weeks fetal gestational age]
Fetal sub-cortical gray matter structures in the brain using fetal MRI
Fetal white matter microstructure measures [32-35 weeks fetal gestational age]
Additional fetal white matter microstructure measures using fetal MRI, including qualitative T2 MRI measures and NODDI metrics
Child hippocampal volume [4 - 24 months of age]
Child hippocampal volume, measured via MRI
Child white matter volume [4 - 24 months of age]
Child white matter volume, measured via MRI
Child white matter microstructure [4 - 24 months of age]
Child white matter microstructure, including myelination, fiber coherence, and architecture, measured via MRI
Child white matter connectivity [4 - 24 months of age]
Child white matter connectivity, measured via MRI
Child functional connectivity [4 - 24 months of age]
Child functional connectivity, measured via MRI
Child cerebral metabolism [4 - 24 months of age]
Child cerebral metabolism, including perfusion and spectroscopy, measured via MRI

Other Outcome Measures

Child auditory brain response (ABR) results [Birth - 4 months of age]
Results on auditory brain response test
Hair cortisol results [Birth]
Results from hair cortisol testing
Maternal depression [Measured from 32-35 weeks fetal gestational age - 24 months offspring age]
Maternal depression, measured via the Edinburgh Post-Natal Depression Scale
Maternal anxiety [Measured from 32-35 weeks fetal gestational age - 24 months offspring age]
Maternal anxiety, measured via State-Trait Anxiety Inventory
Maternal Perceived Stress [Measured from 32-35 weeks fetal gestational age - 24 months offspring age]
Maternal Perceived Stress, measured via the Perceived Stress Scale (PSS-10)
Maternal Empowerment [Measured from 32-35 weeks fetal gestational age - 24 months offspring age]
Maternal empowerment, measured via the SWPER Global Survey
Breastmilk micronutrient analysis [4 months offspring age]
Breastmilk micronutrient analysis, measured via maternal breastmilk samples
Maternal iron status [32 - 35 weeks fetal gestational age]
Maternal iron status, measured via hemoglobin, ferritin and TSAT

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

For the maternal participant in the parent RAPIDIRON Trial - a pregnancy that has not gone beyond the period for obtaining a fetal MRI (by scanning the mother at 32-35 weeks fetal gestational age)
An indication of the pregnant woman's intent to deliver in the study area and to reside there so as to be available not only to complete RAPIDIRON participation but also to allow her and her offspring to participate in ancillary study visits;
Informed consent of the pregnant RAPIDIRON participant for her participation and that of her offspring in this ancillary trial; and
Concurrent participation in the RAPIDIRON-KIDS follow-up study (NCT05504863).

Exclusion Criteria:

If a fetal brain anomaly is found when the maternal participant undergoes an MRI at 32-35 weeks fetal gestational age, the dyad would be excluded from the ancillary study;
If any of the following occur, this would result in dyad ineligibility for participation or continued participation in this ancillary study: maternal blood transfusion after enrollment, a pregnancy ending in stillbirth, neonatal death, diagnosis in the offspring of moderate to severe hypoxic-ischemic encephalopathy (or HIE), and/or blood transfusion to the offspring.