Necrotizing EnterocolitisNCT00392977
Brain Manganese Deposition in High Risk Neonates
An observational study of Necrotizing Enterocolitis and Digestive System Abnormalities, run by Vanderbilt University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 days to 12 months
- Conditions the study is for
- Necrotizing Enterocolitis, Digestive System Abnormalities, Cholestasis
- What is being tested?
- remove Mn from PN if evidence of increased brain Mn on MRI
- How many people
- 43 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 12 months
- All sexes
- No healthy volunteers
- Child
Study population: Neonates in the NICU on prolonged PN
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.
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
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.
Read the 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:
- 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).
- 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.
- 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
- Enterocolitis, Necrotizing, Digestive System Abnormalities, Cholestasis, Hyperphagia, 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
trace element cocktail will be withheld and zinc, copper and chromium added to PN individually.
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between changes in MR signals and dietary Mn intake, number of days on PN and blood Mn levels
Measured: 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.
Measured: at hospital discharge and at 6 months of age
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 (6)Papers the sponsor has linked to this study.
- Other trials for Necrotizing EnterocolitisStudies 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
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Environmental Health Sciences (NIEHS)
- 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
- NCT00392977
- Sponsor's protocol ID
- ES013730
- 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 16099026Erikson 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.
PubMed 17084903Fitsanakis 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
- Brain Manganese Deposition in High Risk Neonates
- ClinicalTrials.gov ID
- NCT00392977
- Acronym / sponsor ID
- ES013730
- Keywords
- Manganese, Neonatal Intensive Care, MRI, Parenteral Nutrition, Prematurity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- National Institute of Environmental Health Sciences (NIEHS)
- 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.
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.
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:
- 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).
- 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.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 30 days to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Neonates in the NICU on prolonged PN
Key inclusion criteria (4 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.
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 MRItrace element cocktail will be withheld and zinc, copper and chromium added to PN individually. | Dietary supplement | – |
Primary outcome
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
1 secondary outcome
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
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 17084903Erikson 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.
- 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 Necrotizing Enterocolitis and Digestive System Abnormalities, 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 4 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?
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). 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 NCT00392977, which also lists 6 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.