Neuroimaging Ancillary Study

Child Development Clinical Trial

Official title:

Neuroimaging Ancillary Study of the IV Iron RAPIDIRON Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05545527
• Other study ID #: U32401
• Status: Active, not recruiting
• Start date: February 21, 2023
• Est. completion date: February 2025

Study information

• Verified date: May 2024
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 184
• Est. completion date: February 2025
• Est. primary completion date: February 14, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron-Deficiency
• Child Development
• Deficiency Diseases
• Iron Deficiency Anemia
• Iron Deficiency Anemia of Pregnancy
• Iron Deficiency Anemia Treatment
• Neurodevelopmental Disorders

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
India	Jawaharlal Nehru Medical College	Belgaum	Karnataka

Sponsors (2)

Lead Sponsor	Collaborator
Thomas Jefferson University	Jawaharlal Nehru Medical College

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Child auditory brain response (ABR) results	Results on auditory brain response test	Birth - 4 months of age
Other	Hair cortisol results	Results from hair cortisol testing	Birth
Other	Maternal depression	Maternal depression, measured via the Edinburgh Post-Natal Depression Scale	Measured from 32-35 weeks fetal gestational age - 24 months offspring age
Other	Maternal anxiety	Maternal anxiety, measured via State-Trait Anxiety Inventory	Measured from 32-35 weeks fetal gestational age - 24 months offspring age
Other	Maternal Perceived Stress	Maternal Perceived Stress, measured via the Perceived Stress Scale (PSS-10)	Measured from 32-35 weeks fetal gestational age - 24 months offspring age
Other	Maternal Empowerment	Maternal empowerment, measured via the SWPER Global Survey	Measured from 32-35 weeks fetal gestational age - 24 months offspring age
Other	Breastmilk micronutrient analysis	Breastmilk micronutrient analysis, measured via maternal breastmilk samples	4 months offspring age
Other	Maternal iron status	Maternal iron status, measured via hemoglobin, ferritin and TSAT	32 - 35 weeks fetal gestational age
Primary	Fetal hippocampal volume	Fetal hippocampus volume, measured via fetal MRI	32-35 weeks fetal gestational age
Primary	Fetal diffusion parameters: fractional anisotropy (FA)	Fetal white matter microstructure will be measured via FA at the posterior limb of internal capsule using fetal MRI	32-35 weeks fetal gestational age
Primary	Fetal diffusion parameters: mean diffusivity	Fetal white matter microstructure will be measured via MD at the posterior limb of internal capsule using fetal MRI	32-35 weeks fetal gestational age
Secondary	Fetal sub-cortical gray matter structures	Fetal sub-cortical gray matter structures in the brain using fetal MRI	32-35 weeks fetal gestational age
Secondary	Fetal white matter microstructure measures	Additional fetal white matter microstructure measures using fetal MRI, including qualitative T2 MRI measures and NODDI metrics	32-35 weeks fetal gestational age
Secondary	Child hippocampal volume	Child hippocampal volume, measured via MRI	4 - 24 months of age
Secondary	Child white matter volume	Child white matter volume, measured via MRI	4 - 24 months of age
Secondary	Child white matter microstructure	Child white matter microstructure, including myelination, fiber coherence, and architecture, measured via MRI	4 - 24 months of age
Secondary	Child white matter connectivity	Child white matter connectivity, measured via MRI	4 - 24 months of age
Secondary	Child functional connectivity	Child functional connectivity, measured via MRI	4 - 24 months of age
Secondary	Child cerebral metabolism	Child cerebral metabolism, including perfusion and spectroscopy, measured via MRI	4 - 24 months of age