Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children

Necrotizing Enterocolitis Clinical Trial

Official title:

Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00392730
• Other study ID #: Gerber07-01-06JLA
• Secondary ID: ES013730
• Status: Completed
• Phase: N/A
• First received: October 25, 2006
• Last updated: December 18, 2013
• Start date: August 2006
• Est. completion date: December 2010

Study information

• Verified date: December 2013
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

Manganese (Mn) is an essential metal required for normal growth and development. However, exposure to high Mn levels can be toxic to the brain. The objectives of this project are to identify neonatal and young pediatric populations that are at increased risk of excessive brain Mn deposition and altered cognitive and motor development based on their dietary parenteral Mn exposure, and to make sound and evidence-based recommendations for appropriate Mn supplementation and monitoring of infants and young children receiving parenteral nutrition (PN). Our studies are designed to test the hypotheses that, compared with unexposed age-matched controls, infants and young children receiving prolonged Mn-supplemented PN will have increased deposition of Mn in their brains and lower scores on neurodevelopmental, cognitive and psychophysiological assessments.

Description:

Specific Aims have been designed to test these hypotheses in three developmentally distinct populations:

1. preterm infants and

2. full term infants in the Neonatal Intensive Care Unit (NICU) requiring prolonged PN and

3. older infants and young children on home PN.

Mn neurotoxicity will be investigated by longitudinal assessments of cognitive (executive functioning battery), neurodevelopmental (Bayley III Scales of Infant Development), and psychophysiological (event-related potential) measures and will be correlated with brain deposition of Mn using the technique of magnetic resonance (MR) relaxometry in a vulnerable population of infants receiving Mn-supplemented PN and age-matched controls. This proposal addresses a clinically relevant and unexplored link between nutritional practices, brain Mn deposition and neurodevelopmental sequelae in an at-risk population of infants and young children utilizing state-of-the-art magnetic resonance imaging (MRI) technology and neurodevelopmental assessment techniques. The potential for increased brain Mn accumulation in infants, and by inference, the potential health risks associated with elevated brain Mn burden, represents crucial, unexplored issues of exposure and susceptibility. The potential contribution of Mn toxicity to the poor outcomes of infants dependent for an extended time on PN has not been fully acknowledged or studied. Improved understanding of the relationships between Mn exposure and developmental outcomes will undoubtedly lead to altered clinical practices and more careful monitoring of Mn intake and blood and/or brain Mn levels in high risk infants. Our studies will also contribute to an improved understanding of the value of non-invasive MR imaging in the monitoring of pediatric patients on PN.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 6 Years

Eligibility

Inclusion Criteria:

1. Greater than 30 days postnatal age

2. In the preceding four weeks, have received >75% of their nutrition as Mn-supplemented PN

3. Clinically stable for transport to the MR facility

4. Signed parental consent.

Or healthy age-matched controls

Exclusion Criteria:

1. Any infant not expected to survive to the age of 3 months or

2. Not expected to achieve sufficient clinical stability to tolerate the MRI procedure.

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Cholestasis
• Digestive System Abnormalities
• Enterocolitis
• Enterocolitis, Necrotizing
• Necrotizing Enterocolitis
• Parenteral Nutrition

Intervention

Dietary Supplement:
• Remove Mn from PN if evidence of increased brain Mn on MRI
Withhold Mn-containing trace element cocktail and add zinc, copper and chromium individually to PN

Locations

Country	Name	City	State
United States	Vanderbilt Children's Hospital	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University	The Gerber Foundation

Country where clinical trial is conducted

United States, 

References & Publications (4)

Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Aspects Med. 2005 Aug-Oct;26(4-5):353-62. Review. — View Citation

Fitsanakis VA, Piccola G, Marreilha dos Santos AP, Aschner JL, Aschner M. Putative proteins involved in manganese transport across the blood-brain barrier. Hum Exp Toxicol. 2007 Apr;26(4):295-302. Review. — View Citation

Fitsanakis VA, Zhang N, Avison MJ, Gore JC, Aschner JL, Aschner M. The use of magnetic resonance imaging (MRI) in the study of manganese neurotoxicity. Neurotoxicology. 2006 Sep;27(5):798-806. Epub 2006 Apr 18. Review. — View Citation

Yin Z, Aschner JL, dos Santos AP, Aschner M. Mitochondrial-dependent manganese neurotoxicity in rat primary astrocyte cultures. Brain Res. 2008 Apr 8;1203:1-11. doi: 10.1016/j.brainres.2008.01.079. Epub 2008 Feb 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain Mn deposition measured by MR relaxometry	Mn neurotoxicity will be investigated by magnetic resonance (MR) relaxometry in a population of infants receiving Mn-supplemented parenteral nutrition and age-matched controls.	baseline (at study enrolment)	No
Secondary	Neurodevelopmental outcomes	Neurodevelopment will be investigated by longitudinal assessments of cognitive (executive functioning battery), neurodevelopmental (Bayley III Scales of Infant Development), and psychophysiological (event-related potential) measures	2 years	No