Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children

This study has been completed.
Sponsor:
Collaborator:
The Gerber Foundation
Information provided by (Responsible Party):
Judy Aschner, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00392730
First received: October 25, 2006
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention
Parenteral Nutrition
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: Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Brain Mn deposition measured by MR relaxometry [ Time Frame: baseline (at study enrolment) ] [ Designated as safety issue: No ]
    Mn neurotoxicity will be investigated by magnetic resonance (MR) relaxometry in a population of infants receiving Mn-supplemented parenteral nutrition and age-matched controls.


Secondary Outcome Measures:
  • Neurodevelopmental outcomes [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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


Biospecimen Retention:   Samples Without DNA

Blood


Enrollment: 122
Study Start Date: August 2006
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
Preterm infants in NICU and age-matched controls
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
2
Term infants in NICU and age-matched controls
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
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
Withhold Mn-containing trace element cocktail and add zinc, copper and chromium individually to PN

Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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

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.

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.
  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: NCT00392730

Locations
United States, Tennessee
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232-9544
Sponsors and Collaborators
Vanderbilt University
The Gerber Foundation
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: NCT00392730     History of Changes
Other Study ID Numbers: Gerber07-01-06JLA, ES013730
Study First Received: October 25, 2006
Last Updated: December 18, 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:
Cholestasis
Digestive System Abnormalities
Enterocolitis
Enterocolitis, Necrotizing
Bile Duct Diseases
Biliary Tract Diseases
Congenital Abnormalities
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on October 22, 2014