Parenteral NutritionNCT00392730
Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children
An observational study of Parenteral Nutrition and Necrotizing Enterocolitis, run by Vanderbilt University at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 30 days to 6 yearsHealthy volunteers can take part
- Conditions the study is for
- Parenteral Nutrition, Necrotizing Enterocolitis, Digestive System Abnormalities
- What is being tested?
- Remove Mn from PN if evidence of increased brain Mn on MRI
- How many people
- 122 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2006to Dec 2010
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 days to 6 years
- All sexes
- Healthy volunteers accepted
- Child
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
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt Children's Hospital
Nashville, Tennessee, 37232-9544
About this study
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.
Read the detailed description
Specific Aims have been designed to test these hypotheses in three developmentally distinct populations:
- preterm infants and
- full term infants in the Neonatal Intensive Care Unit (NICU) requiring prolonged PN and
- 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.
- Conditions
- Parenteral Nutrition, Necrotizing Enterocolitis, Digestive System Abnormalities, Cholestasis
- Being tested
- Remove Mn from PN if evidence of increased brain Mn on MRI
- Keywords
- Manganese, Neonatal Intensive Care, MRI, Parenteral Nutrition, Prematurity
- Medical subject headings
- Hyperphagia, Enterocolitis, Necrotizing, Digestive System Abnormalities, Cholestasis, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remove Mn from PN if evidence of increased brain Mn on MRIDietary supplement
Withhold Mn-containing trace element cocktail and add zinc, copper and chromium individually to PN
| Study group | Role | What they receive |
|---|---|---|
| 1 | Preterm infants in NICU and age-matched controls Receives: Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRI | |
| 2 | Term infants in NICU and age-matched controls Receives: 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 Receives: Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline (at study enrolment)
Secondary outcomes (1)
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2006 (estimated)
- Study startAug 2006
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Parenteral NutritionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- The Gerber Foundation
- Responsible party
- Principal investigator, Judy Aschner, Vanderbilt University
- Investigators
- Judy L Aschner, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00392730
- Sponsor's protocol ID
- Gerber07-01-06JLA
- Other IDs
- ES013730
- Status last verified
- Dec 2013
- First submitted
- 25 Oct 2006
- Last updated
- 19 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 16099026Fitsanakis 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.
PubMed 16620989Fitsanakis 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.
PubMed 17615110Yin 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.
PubMed 18313649Aschner 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.
PubMed 26561627
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children
- ClinicalTrials.gov ID
- NCT00392730
- Acronym / sponsor ID
- Gerber07-01-06JLA
- Conditions
- Parenteral Nutrition, Necrotizing Enterocolitis, Digestive System Abnormalities, Cholestasis
- Keywords
- Manganese, Neonatal Intensive Care, MRI, Parenteral Nutrition, Prematurity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- The Gerber Foundation
- Study start
- Aug 2006
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 26 Oct 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Specific Aims have been designed to test these hypotheses in three developmentally distinct populations:
- preterm infants and
- full term infants in the Neonatal Intensive Care Unit (NICU) requiring prolonged PN and
- 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.
Study design
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRIPreterm infants in NICU and age-matched controls |
| 2 | – | Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRITerm infants in NICU and age-matched controls |
| 3 | – | Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRIChildren on home PN (to age 6) and age-matched controls |
Who may qualify
- Ages
- 30 days to 6 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- 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
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remove Mn from PN if evidence of increased brain Mn on MRIWithhold Mn-containing trace element cocktail and add zinc, copper and chromium individually to PN | Dietary supplement | 1, 2, 3 |
Primary outcome
Brain Mn deposition measured by MR relaxometry
Time frame: baseline (at study enrolment)
Mn neurotoxicity will be investigated by magnetic resonance (MR) relaxometry in a population of infants receiving Mn-supplemented parenteral nutrition and age-matched controls.
1 secondary outcome
Neurodevelopmental outcomes
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2013.
- Background: PubMed 16099026Aschner 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.
- Background: PubMed 16620989Fitsanakis 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.
- Background: PubMed 17615110Fitsanakis 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.
- Background: PubMed 18313649Yin 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.
- Derived from this study: PubMed 26561627Aschner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Judy L Aschner, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parenteral Nutrition and Necrotizing Enterocolitis, run by Vanderbilt University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain Mn deposition measured by MR relaxometry (time frame: baseline (at study enrolment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00392730, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2013.