PrematurityNCT01776268
Effect of Colostrum on Mucosal Immunity in Very Low Birth Weight (VLBWs) Premature Infants
A study testing Oral priming in people with Prematurity, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
Background: Infection in preterm infants is a common, costly, and devastating problem frequently causing death or sequelae for survivors. An immature immune system underlies the frequency and severity of infections in this vulnerable population. Read more about this study
- Who is it for?
- Ages Up to 1 year
- Conditions the study is for
- Prematurity
- What is being tested?
- Oral priming
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to Sep 2016
- 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 Up to 1 year
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Very low birth weight (<1500 g)
- Gestational age <30 weeks
- Admission to NICU (born at Vanderbilt or transferred in for care)
- English or Spanish-speaking parents
Who cannot join
- Does not meet inclusion criteria
- Parent does not give study consent
- Has congenital anomalies, chromosomal disorder or medical contraindication to oral/enteral feedings
Trial locations and contacts
1 site in 1 country.
United States1 site
Monroe Carell Jr Children's Hospital at Vanderbilt University
Nashville, Tennessee, 37232-0656
About this study
Official title: Effect of Colostrum on Innate Mucosal Immunity in Very Premature Infants
Background:
Infection in preterm infants is a common, costly, and devastating problem frequently causing death or sequelae for survivors. An immature immune system underlies the frequency and severity of infections in this vulnerable population. The mouth is the site where microbes first meet the mucosal immune system. Antimicrobial proteins and peptides (APPs) in saliva kill microbes and improve immune cell function. Low APP levels increase the risk of developing infection. Colostrum and human milk reduce the risk of infection. This protective effect of human milk may come from supplying or stimulating infant production of APPs. No prior investigation has determined the concentration of APPs in saliva or the effect of human milk/formula on the APP concentrations in saliva.
Read more
Objective(s) and Hypothesis(es):
The investigators objectives are to identify and serially determine the concentrations of key APPs in colostrum, human milk, and preterm infant saliva using highly-sensitive and specific mass spectroscopy methods. The investigators study is designed to test the hypotheses that (a) all saliva APPs increase over time, (b) APP concentrations are higher in colostrum as compared to human milk, and (c) APPs are increased in saliva of infants that receive colostrum orally compared to those that do not.
Potential Impact:
If increased saliva APP levels are associated with oral colostrum priming, this discovery would advance understanding of the immune properties of human milk and identify oral APPs as important immune elements and potential therapeutic targets in this vulnerable population. This knowledge has the potential to alter feeding practices and provide a safe, low cost means to improve immune function and significantly improve outcomes for preterm infants.
Read the detailed description
Background: Between 20 and 60% of very low birth weight (VLBW) infants are diagnosed with infection during their initial hospitalization2-9. Infection in preterm infants is a costly and devastating problem associated with high mortality and debilitating survivor morbidity. High infection rates are attributed to suboptimal preterm neonatal immune function. In depth investigation of the unique properties of the preterm neonatal immune function is necessary to identify novel interventions that can translate into improved neonatal outcomes.
Mucosal surfaces are critical immune barriers that shield against host microbial invasion by surface-colonizing commensal or potentially pathogenic organisms. Antimicrobial proteins and peptides (APPs) on mucosal surfaces reduce microbial burden individually and synergistically by direct killing of microbes and by improving immune surveillance through activation of local sentinel cells. Deficiencies in these innate immune proteins predispose the host to infection or dysregulated inflammation. Two major classes of APPs (defensins and cathelicidin) are present on mucosal surfaces in adults. Colostrum and human milk (HM) contain some APPs that may play an adjuvant role on mucosal sites including the mouth. HM ingestion is associated with a decreased risk of developing sepsis and necrotizing enterocolitis in preterm infants. One potential mechanism behind the reduction in infection risk associated with HM feeding may be enhanced immunocompetence through provision of APPs and induction of neonatal APP production. Investigators are not aware of any investigation that has determined the neonatal salivary concentration of any APP or the effect of oral priming (OP) with colostrum on the concentration of salivary APPs. It is also unknown whether OP with formula modifies salivary APPs.
Objectives and Hypotheses: Our objectives are to determine: 1) the concentration of salivary APPs from preterm infants at baseline and 7 days later, 2) the effect of oral priming (OP) with either human milk or formula on salivary APP concentrations, and 3) the concentration of APPs in colostrum as compared to milk. Our hypotheses are: 1) All salivary APPs increase over time in preterm infants (with or without OP) 2) Compared with formula OP or no OP, colostrum OP is associated with a significantly greater increase in salivary LL-37 and hBD2 concentrations and 3) Colostrum contains a greater concentration of LL-37 compared to human milk.
Design: Following the mother's decision to provide human milk or formula to her preterm newborn, VLBW infants will be randomized to receive OP or not. Investigators will compare the concentration of salivary APPs from VLBW infants that receive OP to VLBW infants that do not. Saliva will be sampled prior to and after 5 days of OP. Time-matched saliva samples will be obtained from the infants that do not receive OP. APP concentrations will be compared between the biological mother's colostrum (both whey and fat fractions) and her transitional milk (produced >7 days after birth). To account for the heterogeneous VLBW population, investigators will study 200 infants (50 infants/group, 4 groups) to test our hypotheses. Both inborn and outborn VLBW infants are eligible. Exclusion criteria include infants with a medical contraindication for oral or enteral feeds, congenital anomalies or chromosomal disorders. Saliva and milk-based proteomes including APPs will be determined using Matrix Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF).
Potential Impact: This is the first study of APPs in saliva of human neonates. If increased saliva APP levels are associated with colostrum OP, this discovery would add to our understanding of the immune properties of human milk. Identification of APPs as important elements that improve immune function is likely to alter the approach to infant nutrition and improve outcomes for premature infants. Ultimately, our goal is to determine whether there is an association between APP levels in neonatal saliva and the incidence of neonatal infection (including NEC) in an appropriately powered clinical study based on the data generated in this proposal.
- Conditions
- Prematurity
- Being tested
- Oral priming
- Keywords
- antimicrobial proteins
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral primingOther
Mother's own colostrum is administered (0.1 mL to each cheek every 6 hours for 5 days) as soon as it is available from the mother regardless of when enteral feedings are initiated.
| Study group | Role | What they receive |
|---|---|---|
| Oral priming | Experimental | Mother's own colostrum is administered (0.1 mL to each cheek every 6 hours for 5 days) as soon as it is available from the mother regardless of when enteral feedings are initiated. Receives: Other: Oral priming |
| No oral priming | No intervention | No oral priming |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of APPs Before Oral Priming
Saliva will be sampled on day 1-2 of life prior to oral priming. Investigators are assessing saliva for a change in the concentration of antimicrobial proteins.
Measured: days 1-2 of life
Concentration of APPs After Oral Priming
Saliva will be sampled 24-48 hours after the 5-days of oral priming is completed. Investigators are assessing saliva for a change in the concentration of antimicrobial proteins.
Measured: days 7-9 of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2013 (estimated)
- Study startFeb 2013
- Primary completionMar 2015
- Study completionSep 2016
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 (1)Papers the sponsor has linked to this study.
- Other trials for PrematurityStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe 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
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Thrasher Research Fund
- Responsible party
- Principal investigator, James Wynn, Vanderbilt University Medical Center
- Investigators
- James L Wynn, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01776268
- Sponsor's protocol ID
- 121760
- Status last verified
- Jun 2017
- First submitted
- 17 Jan 2013
- Last updated
- 7 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Romano-Keeler J, Azcarate-Peril MA, Weitkamp JH, Slaughter JC, McDonald WH, Meng S, Latuga MS, Wynn JL. Oral colostrum priming shortens hospitalization without changing the immunomicrobial milieu. J Perinatol. 2017 Jan;37(1):36-41. doi: 10.1038/jp.2016.161. Epub 2016 Sep 29.
PubMed 27684425
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Colostrum on Innate Mucosal Immunity in Very Premature Infants
- ClinicalTrials.gov ID
- NCT01776268
- Acronym / sponsor ID
- 121760
- Conditions
- Prematurity
- Keywords
- antimicrobial proteins
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- Thrasher Research Fund
- Study start
- Feb 2013 (actual)
- Primary completion
- Mar 2015 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 28 Jan 2013 (estimated)
- Results
- Posted 7 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Infection in preterm infants is a common, costly, and devastating problem frequently causing death or sequelae for survivors. An immature immune system underlies the frequency and severity of infections in this vulnerable population. The mouth is the site where microbes first meet the mucosal immune system. Antimicrobial proteins and peptides (APPs) in saliva kill microbes and improve immune cell function. Low APP levels increase the risk of developing infection. Colostrum and human milk reduce the risk of infection. This protective effect of human milk may come from supplying or stimulating infant production of APPs. No prior investigation has determined the concentration of APPs in saliva or the effect of human milk/formula on the APP concentrations in saliva.
Objective(s) and Hypothesis(es):
The investigators objectives are to identify and serially determine the concentrations of key APPs in colostrum, human milk, and preterm infant saliva using highly-sensitive and specific mass spectroscopy methods. The investigators study is designed to test the hypotheses that (a) all saliva APPs increase over time, (b) APP concentrations are higher in colostrum as compared to human milk, and (c) APPs are increased in saliva of infants that receive colostrum orally compared to those that do not.
Potential Impact:
If increased saliva APP levels are associated with oral colostrum priming, this discovery would advance understanding of the immune properties of human milk and identify oral APPs as important immune elements and potential therapeutic targets in this vulnerable population. This knowledge has the potential to alter feeding practices and provide a safe, low cost means to improve immune function and significantly improve outcomes for preterm infants.
Detailed description
Background: Between 20 and 60% of very low birth weight (VLBW) infants are diagnosed with infection during their initial hospitalization2-9. Infection in preterm infants is a costly and devastating problem associated with high mortality and debilitating survivor morbidity. High infection rates are attributed to suboptimal preterm neonatal immune function. In depth investigation of the unique properties of the preterm neonatal immune function is necessary to identify novel interventions that can translate into improved neonatal outcomes.
Mucosal surfaces are critical immune barriers that shield against host microbial invasion by surface-colonizing commensal or potentially pathogenic organisms. Antimicrobial proteins and peptides (APPs) on mucosal surfaces reduce microbial burden individually and synergistically by direct killing of microbes and by improving immune surveillance through activation of local sentinel cells. Deficiencies in these innate immune proteins predispose the host to infection or dysregulated inflammation. Two major classes of APPs (defensins and cathelicidin) are present on mucosal surfaces in adults. Colostrum and human milk (HM) contain some APPs that may play an adjuvant role on mucosal sites including the mouth. HM ingestion is associated with a decreased risk of developing sepsis and necrotizing enterocolitis in preterm infants. One potential mechanism behind the reduction in infection risk associated with HM feeding may be enhanced immunocompetence through provision of APPs and induction of neonatal APP production. Investigators are not aware of any investigation that has determined the neonatal salivary concentration of any APP or the effect of oral priming (OP) with colostrum on the concentration of salivary APPs. It is also unknown whether OP with formula modifies salivary APPs.
Objectives and Hypotheses: Our objectives are to determine: 1) the concentration of salivary APPs from preterm infants at baseline and 7 days later, 2) the effect of oral priming (OP) with either human milk or formula on salivary APP concentrations, and 3) the concentration of APPs in colostrum as compared to milk. Our hypotheses are: 1) All salivary APPs increase over time in preterm infants (with or without OP) 2) Compared with formula OP or no OP, colostrum OP is associated with a significantly greater increase in salivary LL-37 and hBD2 concentrations and 3) Colostrum contains a greater concentration of LL-37 compared to human milk.
Design: Following the mother's decision to provide human milk or formula to her preterm newborn, VLBW infants will be randomized to receive OP or not. Investigators will compare the concentration of salivary APPs from VLBW infants that receive OP to VLBW infants that do not. Saliva will be sampled prior to and after 5 days of OP. Time-matched saliva samples will be obtained from the infants that do not receive OP. APP concentrations will be compared between the biological mother's colostrum (both whey and fat fractions) and her transitional milk (produced >7 days after birth). To account for the heterogeneous VLBW population, investigators will study 200 infants (50 infants/group, 4 groups) to test our hypotheses. Both inborn and outborn VLBW infants are eligible. Exclusion criteria include infants with a medical contraindication for oral or enteral feeds, congenital anomalies or chromosomal disorders. Saliva and milk-based proteomes including APPs will be determined using Matrix Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF).
Potential Impact: This is the first study of APPs in saliva of human neonates. If increased saliva APP levels are associated with colostrum OP, this discovery would add to our understanding of the immune properties of human milk. Identification of APPs as important elements that improve immune function is likely to alter the approach to infant nutrition and improve outcomes for premature infants. Ultimately, our goal is to determine whether there is an association between APP levels in neonatal saliva and the incidence of neonatal infection (including NEC) in an appropriately powered clinical study based on the data generated in this proposal.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral priming | Experimental | Other: Oral primingMother's own colostrum is administered (0.1 mL to each cheek every 6 hours for 5 days) as soon as it is available from the mother regardless of when enteral feedings are initiated. |
| No oral priming | No intervention | –No oral priming |
Who may qualify
- Ages
- Up to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Very low birth weight (<1500 g)
- Gestational age <30 weeks
- Admission to NICU (born at Vanderbilt or transferred in for care)
- English or Spanish-speaking parents
Key exclusion criteria (3 listed)
- Does not meet inclusion criteria
- Parent does not give study consent
- Has congenital anomalies, chromosomal disorder or medical contraindication to oral/enteral feedings
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 |
|---|---|---|
| Oral primingMother's own colostrum is administered (0.1 mL to each cheek every 6 hours for 5 days) as soon as it is available from the mother regardless of when enteral feedings are initiated. | Other | Oral priming |
Primary outcome
Concentration of APPs Before Oral Priming
Time frame: days 1-2 of life
Saliva will be sampled on day 1-2 of life prior to oral priming. Investigators are assessing saliva for a change in the concentration of antimicrobial proteins.
Concentration of APPs After Oral Priming
Time frame: days 7-9 of life
Saliva will be sampled 24-48 hours after the 5-days of oral priming is completed. Investigators are assessing saliva for a change in the concentration of antimicrobial proteins.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27684425Romano-Keeler J, Azcarate-Peril MA, Weitkamp JH, Slaughter JC, McDonald WH, Meng S, Latuga MS, Wynn JL. Oral colostrum priming shortens hospitalization without changing the immunomicrobial milieu. J Perinatol. 2017 Jan;37(1):36-41. doi: 10.1038/jp.2016.161. Epub 2016 Sep 29.
- Oral colostrum priming shortens hospitalization without changing the immunomicrobial milieuLink provided by the sponsor.
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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.
James L Wynn, MD principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oral priming in people with Prematurity, run by Vanderbilt University Medical Center 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 3 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 7 Jul 2017. 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 Jul 2017). 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?
Concentration of APPs Before Oral Priming (time frame: days 1-2 of life). 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 NCT01776268, which also lists 1 linked publication.
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 7 Jul 2017.