Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children

NCT00392730 | Completed DMC

• 2 other identifiers: Gerber07-01-06JLAES013730
• Study Type: observational
• Target: 122
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Parenteral Nutrition; Necrotizing Enterocolitis; Digestive System Abnormalities; Cholestasis

Keywords

Manganese; Neonatal Intensive Care; MRI; Parenteral Nutrition; Prematurity

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (1)

• Neurodevelopmental outcomes

  2 years

Study Arms (3)

1

Preterm infants in NICU and age-matched controls

Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRI

2

Term infants in NICU and age-matched controls

Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRI

3

Children on home PN (to age 6) and age-matched controls

Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRI

Interventions

Remove Mn from PN if evidence of increased brain Mn on MRI DIETARY_SUPPLEMENT

Withhold Mn-containing trace element cocktail and add zinc, copper and chromium individually to PN

1; 2; 3

Eligibility Criteria

• Age: 30 Days - 6 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Term and preterm infants on prolonged PN in the NICU and post-discharge and young children on home PN and age-matched controls

You may qualify if:

• Greater than 30 days postnatal age
• In the preceding four weeks, have received \>75% of their nutrition as Mn-supplemented PN
• Clinically stable for transport to the MR facility
• Signed parental consent.
• Or healthy age-matched controls

You may not qualify if:

• Any infant not expected to survive to the age of 3 months or
• Not expected to achieve sufficient clinical stability to tolerate the MRI procedure.

Sponsors & Collaborators

• Vanderbilt University: lead
• The Gerber Foundation: collaborator

Study Sites (1)

Vanderbilt Children's Hospital

Nashville, Tennessee, 37232-9544, United States

Location

Related Publications (5)

• Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Aspects Med. 2005 Aug-Oct;26(4-5):353-62. doi: 10.1016/j.mam.2005.07.003.

  PMID: 16099026 BACKGROUND

• 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. doi: 10.1016/j.neuro.2006.03.001. Epub 2006 Apr 18.

  PMID: 16620989 BACKGROUND

• 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. doi: 10.1177/0960327107070496.

  PMID: 17615110 BACKGROUND

• 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.

  PMID: 18313649 BACKGROUND

• Aschner JL, Anderson A, Slaughter JC, Aschner M, Steele S, Beller A, Mouvery A, Furlong HM, Maitre NL. Neuroimaging identifies increased manganese deposition in infants receiving parenteral nutrition. Am J Clin Nutr. 2015 Dec;102(6):1482-9. doi: 10.3945/ajcn.115.116285. Epub 2015 Nov 11.

  PMID: 26561627 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood

MeSH Terms

Conditions

Hyperphagia; Enterocolitis, Necrotizing; Digestive System Abnormalities; Cholestasis; Premature Birth

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bile Duct Diseases; Biliary Tract Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Judy L Aschner, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Adjunct Professor of Pediatrics

Study Record Dates

• First Submitted: October 25, 2006
• First Posted: October 26, 2006
• Study Start: August 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: December 19, 2013

Record last verified: 2013-12

Locations

US (1)