Trial record 10 of 29 for:    necrotizing enterocolitis | NIH

Brain Manganese Deposition in High Risk Neonates

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Judy Aschner, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00392977
First received: October 25, 2006
Last updated: December 17, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention
Necrotizing Enterocolitis
Digestive System Abnormalities
Cholestasis
Dietary Supplement: remove Mn from PN if evidence of increased brain Mn on MRI

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Brain Manganese Deposition in High Risk Neonates

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Correlation between changes in MR signals and dietary Mn intake, number of days on PN and blood Mn levels [ Time Frame: at hospital discharge and 6 months of age ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of pallidal-white matter T1 ratios and absolute T1 and T2 values in control infants and neonates receiving Mn-supplemented PN. [ Time Frame: at hospital discharge and at 6 months of age ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Blood


Enrollment: 43
Study Start Date: August 2006
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Dietary Supplement: remove Mn from PN if evidence of increased brain Mn on MRI
    trace element cocktail will be withheld and zinc, copper and chromium added to PN individually.
Detailed Description:

Manganese (Mn) is an essential metal needed for normal growth and development. Excessive environmental or dietary exposure results in Mn deposition in Mn-sensitive brain regions causing adverse psychological and 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, PN bypasses the normal intestinal absorptive control and biliary excretory mechanisms for Mn, and infants are at a critical stage of brain development. Furthermore, iron (Fe) deficiency, a common problem among sick neonates, increases Mn brain uptake because Mn and Fe compete for the same carrier transport systems in the central nervous system. This proposal will investigate brain deposition of Mn, a paramagnetic element, by magnetic resonance (MR) imaging in 40 neonates receiving Mn-supplemented PN and 10 control infants.

Two specific aims will test the following hypotheses:

  1. Shortening of MR T1 and T2 relaxation times (a marker for Mn) in Mn-sensitive brain regions in neonates receiving PN will correlate directly with

    • dietary Mn intake,
    • days on PN,
    • blood Mn levels (measured by Inductively Coupled Plasma-Mass Spectrometry)
    • hepatic dysfunction/cholestasis (assessed by conjugated bilirubin levels).
  2. shortening of T1 and T2 relaxation times will correlate inversely with

    • gestational age
    • Fe status (assessed by serum Fe, ferritin, transferrin, soluble transferrin receptor and hemoglobin).

The potential for increased brain Mn accumulation in infants and the potential health risks associated with elevated brain Mn burden represent crucial, unexplored issues of exposure and susceptibility. The impact of dietary Mn, and especially parenterally delivered dietary Mn, gestational age, Fe status, and hepatic dysfunction on the ability of the neonatal brain to regulate Mn deposition has not been scientifically addressed. The proposed clinical investigation has enormous health significance and may shed light on the development and progression of neurological dysfunction in infants and children on prolonged parenteral nutrition.

  Eligibility

Ages Eligible for Study:   up to 12 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Neonates in the NICU on prolonged PN

Criteria

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.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00392977

Locations
United States, Tennessee
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232-9544
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Judy L Aschner, MD Vanderbilt University
  More Information

Publications:
Responsible Party: Judy Aschner, Adjunct Professor of Pediatrics, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00392977     History of Changes
Other Study ID Numbers: ES013730, ES013730
Study First Received: October 25, 2006
Last Updated: December 17, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Manganese
Neonatal Intensive Care
MRI
Parenteral Nutrition
Prematurity

Additional relevant MeSH terms:
Enterocolitis
Enterocolitis, Necrotizing
Congenital Abnormalities
Cholestasis
Digestive System Abnormalities
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Intestinal Diseases
Manganese
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014