Brain Manganese Deposition in High Risk Neonates

NCT00392977 | Completed DMC

• 1 other identifier: ES013730
• Study Type: observational
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Excessive exposure to manganese (Mn) results in Mn deposition in the brain causing adverse neurological effects. Sick infants requiring parenteral nutrition (PN) may be at increased risk of Mn neurotoxicity because neonatal PN solutions contain high concentrations of Mn. This proposal will investigate brain deposition of Mn, a paramagnetic element, by magnetic resonance (MR) imaging in preterm and term neonates receiving Mn-supplemented PN and gestational age-matched control infants. The goals of this project are to identify neonatal populations that are at increased risk of excessive brain Mn deposition based on their gestational age, iron status, hepatic function and dietary Mn intake, and to make evidence-based recommendations for appropriate Mn supplementation and monitoring of infants receiving PN.

Conditions

Necrotizing Enterocolitis; Digestive System Abnormalities; Cholestasis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Correlation between changes in MR signals and dietary Mn intake, number of days on PN and blood Mn levels

  at hospital discharge and 6 months of age

Secondary Outcomes (1)

• Comparison of pallidal-white matter T1 ratios and absolute T1 and T2 values in control infants and neonates receiving Mn-supplemented PN.

  at hospital discharge and at 6 months of age

Interventions

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

trace element cocktail will be withheld and zinc, copper and chromium added to PN individually.

Eligibility Criteria

• Age: 30 Days - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Neonates in the NICU on prolonged PN

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.

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
• National Institute of Environmental Health Sciences (NIEHS): collaborator

Study Sites (1)

Vanderbilt Children's Hospital

Nashville, Tennessee, 37232-9544, United States

Location

Related Publications (6)

• 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

• Erikson KM, Thompson K, Aschner J, Aschner M. Manganese neurotoxicity: a focus on the neonate. Pharmacol Ther. 2007 Feb;113(2):369-77. doi: 10.1016/j.pharmthera.2006.09.002. Epub 2006 Sep 22.

  PMID: 17084903 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

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

Condition Hierarchy (Ancestors)

Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bile Duct Diseases; Biliary Tract Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; 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)