PrematurityNCT00828451

Collaborative Research Group for Necrotizing Enterocolitis

A study testing [5,5,5-2H3]leucine (stable isotope labeled leucine) in people with Prematurity and Necrotizing Enterocolitis, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This proposal will test the hypothesis that synthesis and catabolism of epidermal growth factor (EGF), the genotype of the EGF gene, and the microbiome interact to influence EGF expression in infants at risk for necrotizing enterocolitis (NEC). Read more about this study

Who is it for?: Ages 1 day to 7 days
Conditions the study is for: Prematurity, Necrotizing Enterocolitis
What is being tested?: [5,5,5-2H3]leucine (stable isotope labeled leucine)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 29 participants
Where: 1 siteUnited States
Study dates: May 2008to Dec 2010
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 1 day to 7 days
All sexes
No healthy volunteers
Child

Who may be able to join

gestation 32 weeks or less
1 week of age or less
intravenous line in place for clinical purposes

Who cannot join

imminent death
active infection
pre-existing diagnosis of NEC
fluid or electrolyte imbalance

Trial locations and contacts

1 site in 1 country.

United States1 site

St. Louis Children's Hospital
St Louis, Missouri, 63110

Other trials in United States

About this study

Read the detailed description

Preterm infants will receive a six hour intravenous infusion of [5,5,5-2H3]leucine (2H3) through an existing intravenous line (IV) to measure EGF synthesis rate.
Two blood samples will be obtained, one prior to the start of infusion, and one during the infusion. The enrichment of the stable isotope labeled leucine will be measured in the plasma from these samples; DNA will be extracted from the residual cell pellets. The EGF and EGF receptor genes will be sequenced.
Saliva and urine will be obtained for 5 days following infusion to measure EGF and the rate of incorporation of leucine into EGF using liquid chromatography (LC)/mass spectroscopy (MS)/MS technology, as well as enzyme-linked immunosorbent assay (ELISA) . Saliva will be obtained by a Q tip swab and urine and stool obtained from the diaper.
Stool will be obtained every 3 to 7 days through 5 weeks to evaluate inflammatory markers and the microbiome.
If breastfeeding, a single sample of mother's milk will be obtained for measurement of EGF after adequate volumes for infant feeds are achieved.

Conditions: Prematurity, Necrotizing Enterocolitis
Being tested: [5,5,5-2H3]leucine (stable isotope labeled leucine)
Keywords: newborn, necrotizing enterocolitis, genetics, growth factors, metabolism
Medical subject headings: Premature Birth, Enterocolitis, Necrotizing

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

[5,5,5-2H3]leucine (stable isotope labeled leucine)Biological
intravenous infusion of labeled leucine dissolved in 5% glucose water: priming dose of 18 micromoles (1.8 ml)/kg over 5 minutes, then 18 micromoles (1.8 ml)/hr for 6 hours; one infusion total

Study groups in NCT00828451
Study group	Role	What they receive
Preterm Infants for EGF Profiles	Experimental	Premature infants born at < 32 weeks gestation who are 7 days old or less. Infants received and intravenous infusion of [5,5,5-2H3]leucine (stable isotope labeled leucine) with sampling of blood, urine and saliva. Receives: Biological: [5,5,5-2H3]leucine (stable isotope labeled leucine)

What is being measured

The primary outcome is the main question the study is designed to answer.

Salivary EGF (Epidermal Growth Factor) Protein Levels
Salivary EGF protein levels obtained from oral swabs were analyzed by commercially available EGF ELISA kit (R \&D systems Inc). EGF protein levels were normalized to micrograms of protein in saliva, and expressed as picogram of EGF protein per microgram of total salivary protein.
Measured: Sampling occurred on average day of life 9 with a range from day of life 7 to 21
Urinary EGF Protein Levels
Urinary EGF protein levels obtained from free flowing urine samples retrieved from subject diaper were analyzed by commercially available EGF ELISA kit (R \&D systems Inc). EGF protein levels were normalized to milligrams of creatinine in urine, and expressed as nanograms of EGF protein per milligram of urinary creatinine.
Measured: Sampling occurred on average day of life 9 with a range from day of life 7 to 21

Secondary outcomes (1)

EGF Gene Sequencing
Identification of computationally predicted functional variants in EGF gene
Measured: Sampling occurred on average day of life 9 with a range from day of life 7 to 21

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2008Dec 2010

First posted26 Jan 2009 (estimated)
Study startMay 2008
Primary completionDec 2009
Study completionDec 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for PrematurityStudies of the same condition, open and under way.
More trials run by Washington University School of MedicineThe sponsor's other registered studies.
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: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00828451
Sponsor's protocol ID: 08-0105
Status last verified: Mar 2018
First submitted: 22 Jan 2009
Last updated: 4 Apr 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Nair RR, Warner BB, Warner BW. Role of epidermal growth factor and other growth factors in the prevention of necrotizing enterocolitis. Semin Perinatol. 2008 Apr;32(2):107-13. doi: 10.1053/j.semperi.2008.01.007.
PubMed 18346534
Warner BB, Ryan AL, Seeger K, Leonard AC, Erwin CR, Warner BW. Ontogeny of salivary epidermal growth factor and necrotizing enterocolitis. J Pediatr. 2007 Apr;150(4):358-63. doi: 10.1016/j.jpeds.2006.11.059.
PubMed 17382110
Spence KL, Zozobrado JC, Patterson BW, Hamvas A. Substrate utilization and kinetics of surfactant metabolism in evolving bronchopulmonary dysplasia. J Pediatr. 2005 Oct;147(4):480-5. doi: 10.1016/j.jpeds.2005.04.039.
PubMed 16227034
Bohlin K, Patterson BW, Spence KL, Merchak A, Zozobrado JC, Zimmermann LJ, Carnielli VP, Hamvas A. Metabolic kinetics of pulmonary surfactant in newborn infants using endogenous stable isotope techniques. J Lipid Res. 2005 Jun;46(6):1257-65. doi: 10.1194/jlr.M400481-JLR200. Epub 2005 Mar 16.
PubMed 15772427

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Prematurity trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Collaborative Research Group for Necrotizing Enterocolitis
ClinicalTrials.gov ID: NCT00828451
Acronym / sponsor ID: 08-0105
Conditions: Prematurity, Necrotizing Enterocolitis
Keywords: newborn, necrotizing enterocolitis, genetics, growth factors, metabolism
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: Washington University School of MedicineUniversity, hospital or other
Study start: May 2008
Primary completion: Dec 2009 (actual)
Study completion: Dec 2010 (actual)
First posted: 26 Jan 2009 (estimated)
Results: Posted 7 Mar 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Preterm infants will receive a six hour intravenous infusion of [5,5,5-2H3]leucine (2H3) through an existing intravenous line (IV) to measure EGF synthesis rate.
Two blood samples will be obtained, one prior to the start of infusion, and one during the infusion. The enrichment of the stable isotope labeled leucine will be measured in the plasma from these samples; DNA will be extracted from the residual cell pellets. The EGF and EGF receptor genes will be sequenced.
Saliva and urine will be obtained for 5 days following infusion to measure EGF and the rate of incorporation of leucine into EGF using liquid chromatography (LC)/mass spectroscopy (MS)/MS technology, as well as enzyme-linked immunosorbent assay (ELISA) . Saliva will be obtained by a Q tip swab and urine and stool obtained from the diaper.
Stool will be obtained every 3 to 7 days through 5 weeks to evaluate inflammatory markers and the microbiome.
If breastfeeding, a single sample of mother's milk will be obtained for measurement of EGF after adequate volumes for infant feeds are achieved.

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Preterm Infants for EGF Profiles	Experimental	Biological: [5,5,5-2H3]leucine (stable isotope labeled leucine)Premature infants born at < 32 weeks gestation who are 7 days old or less. Infants received and intravenous infusion of [5,5,5-2H3]leucine (stable isotope labeled leucine) with sampling of blood, urine and saliva.

Who may qualify

Ages: 1 day to 7 days
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

gestation 32 weeks or less
1 week of age or less
intravenous line in place for clinical purposes

Key exclusion criteria (4 listed)

imminent death
active infection
pre-existing diagnosis of NEC
fluid or electrolyte imbalance

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
[5,5,5-2H3]leucine (stable isotope labeled leucine)intravenous infusion of labeled leucine dissolved in 5% glucose water: priming dose of 18 micromoles (1.8 ml)/kg over 5 minutes, then 18 micromoles (1.8 ml)/hr for 6 hours; one infusion total	Biological	Preterm Infants for EGF Profiles

Primary outcome

Salivary EGF (Epidermal Growth Factor) Protein Levels
Time frame: Sampling occurred on average day of life 9 with a range from day of life 7 to 21
Salivary EGF protein levels obtained from oral swabs were analyzed by commercially available EGF ELISA kit (R \&D systems Inc). EGF protein levels were normalized to micrograms of protein in saliva, and expressed as picogram of EGF protein per microgram of total salivary protein.
Urinary EGF Protein Levels
Time frame: Sampling occurred on average day of life 9 with a range from day of life 7 to 21
Urinary EGF protein levels obtained from free flowing urine samples retrieved from subject diaper were analyzed by commercially available EGF ELISA kit (R \&D systems Inc). EGF protein levels were normalized to milligrams of creatinine in urine, and expressed as nanograms of EGF protein per milligram of urinary creatinine.

1 secondary outcome

EGF Gene Sequencing
Time frame: Sampling occurred on average day of life 9 with a range from day of life 7 to 21

Results and safety

Results posted to the registry on 7 Mar 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Preterm Infants for EGF Profiles	29	18

Primary outcome: Salivary EGF (Epidermal Growth Factor) Protein Levels

Time frame: Sampling occurred on average day of life 9 with a range from day of life 7 to 21. Median (Full Range). Unit: picograms EGF/ microgram of protein

Measure	Preterm Infants for EGF Profiles n = 18
Value	15 (6 to 61)

Population analysed: 29 subjects were enrolled with 11 not completing the study and not analyzed due to lack of specimens

Primary outcome: Urinary EGF Protein Levels

Time frame: Sampling occurred on average day of life 9 with a range from day of life 7 to 21. Median (Full Range). Unit: nanograms of EGF/mg of creatinine

Measure	Preterm Infants for EGF Profiles n = 18
Value	48 (7 to 146)

Population analysed: 29 subjects were enrolled; 11 did not complete the study and were not analyzed

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 20 months (5/1/2008 to 12/31/2009). Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Preterm Infants for EGF Profile	0 of 29 (0%)	0 of 29 (0%)	1 of 29

Limitations and caveats (from the sponsor): stable isotope labeled EGF could not be detected in the urine and thus the project was closed

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 18346534Nair RR, Warner BB, Warner BW. Role of epidermal growth factor and other growth factors in the prevention of necrotizing enterocolitis. Semin Perinatol. 2008 Apr;32(2):107-13. doi: 10.1053/j.semperi.2008.01.007.
Background: PubMed 17382110Warner BB, Ryan AL, Seeger K, Leonard AC, Erwin CR, Warner BW. Ontogeny of salivary epidermal growth factor and necrotizing enterocolitis. J Pediatr. 2007 Apr;150(4):358-63. doi: 10.1016/j.jpeds.2006.11.059.
Background: PubMed 16227034Spence KL, Zozobrado JC, Patterson BW, Hamvas A. Substrate utilization and kinetics of surfactant metabolism in evolving bronchopulmonary dysplasia. J Pediatr. 2005 Oct;147(4):480-5. doi: 10.1016/j.jpeds.2005.04.039.
Background: PubMed 15772427Bohlin K, Patterson BW, Spence KL, Merchak A, Zozobrado JC, Zimmermann LJ, Carnielli VP, Hamvas A. Metabolic kinetics of pulmonary surfactant in newborn infants using endogenous stable isotope techniques. J Lipid Res. 2005 Jun;46(6):1257-65. doi: 10.1194/jlr.M400481-JLR200. Epub 2005 Mar 16.

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Recruiting
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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.

Aaron Hamvas, MD principal investigator

Washington University School of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 3 inclusion and 4 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 4 Apr 2018. 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?

Yes. Results are posted in the registry (first posted 7 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Salivary EGF (Epidermal Growth Factor) Protein Levels (time frame: Sampling occurred on average day of life 9 with a range from day of life 7 to 21). The study lists 2 primary outcomes in all. 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 NCT00828451, which also lists 4 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 4 Apr 2018.