Neuroimaging Ancillary Study

NCT ID: NCT05545527

Last Updated: 2025-04-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 184 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-02-21
• Study Completion Date: 2025-04-07

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.

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.

Conditions

Iron Deficiency Anemia; Iron Deficiency Anemia of Pregnancy; Neurodevelopmental Disorder of Foetus; Iron Deficiency Anemia Treatment; Fetal Neurodevelopmental Disorder; Child Development

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Ferric carboxymaltose

Intervention Type: DRUG

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.

Iron isomaltoside

Intervention Type: DRUG

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.

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.

Ferric Sulfate

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Ferric derisomaltose; Ferric sulphate

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Jawaharlal Nehru Medical College

OTHER

Sponsor Role: collaborator

Thomas Jefferson University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Derman, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Locations

Jawaharlal Nehru Medical College

Belagavi, Karnataka, India

Countries

India

Other Identifiers

U32401

Identifier Type: -

Identifier Source: org_study_id