- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04130165
Matching Donor Human Milk On Maternal Secretor Status (MMOMSS) Study (MMOMSS)
Optimizing the Prebiotic Profile of Donor Human Milk for Preterm Infants: Feasibility of a New Donor Milk Matching Strategy Based on Maternal Secretor Status
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background: The gut microbiome is established early in life and plays an important role in developing the immune system and metabolism. Infants born prematurely (before 37-weeks gestation) account for 1 in 10 births worldwide and are especially vulnerable to serious microbiome-mediated illnesses such as necrotizing enterocolitis and metabolic diseases. Breastfeeding is the most important factor shaping the infant gut microbiome, providing human milk oligosaccharides (HMOs) that serve as prebiotics for beneficial gut bacteria. Donor human milk (DHM) is considered the best alternative when mothers own milk (MOM) is not available. HMO profiles are highly variable between mothers and there is currently no "matching" process to optimize pairing of DHM and recipient infants. The strongest factor influencing HMO composition is maternal secretor status, determined by the expression of a specific gene (α-1, 2-fucosyltransferase-2). About 20% of Caucasians are non-secretors and researchers do not know the impact of feeding DHM from secretor donors to infants of non-secretor mothers. In this study, investigators aim to explore if matching DHM based on maternal secretor status impacts the development of the gut microbiome in preterm infants.
Method: Investigators will use a pilot, randomized, controlled trial to compare three groups of preterm infants (<34 weeks gestation): 1) infants receiving DHM matched to their mother's secretor status, 2) infants receiving standard issue (i.e. unmatched) DHM, and 3) infants who do not require DHM because they are exclusively receiving MOM. Mothers <34 weeks gestation admitted to antenatal units and the labour and delivery units will be screened for eligibility. Enrolled mothers will be randomized to either the intervention (n=30; matched DHM) or control group (n=30; standard unmatched DHM). Infants of mothers assigned to the intervention group will receive "matched" DHM based on maternal secretor status, determined after randomization. Infant fecal samples will be collected weekly from soiled diapers until discontinuation of DHM or discharge/transfer from the unit. Samples of MOM and DHM will also be collected to analyze milk for HMO and nutrient content. Microbial DNA will be analyzed using 16S sequencing. Additionally, for a subset of samples selected based on 16S results, investigators will perform shotgun metagenomics to identify microbial population structures and functional capacity. Microbial composition from intervention (matched DHM), control (unmatched DHM) and reference (exclusive MOM) groups will be compared to determine differences in microbial diversity and taxonomy.
Impact on healthcare: If promising, investigators would like to examine this phenomenon in a much larger cohort of preterm infants from NICUs across Canada. This research could revolutionize how milk banks and neonatal intensive care units provide DHM to preterm infants. Finally, this research will expand on understanding of the prebiotic effects of HMOs on infant microbiome and may inform future prebiotic/probiotic supplementation regimens.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Meredith L Brockway, PhD
- Phone Number: 4036890970
- Email: mbrockwa@ucalgary.ca
Study Contact Backup
- Name: Meghan B Azad, PhD
- Phone Number: +1 (204) 975-7754
- Email: meghan.azad@umanitoba.ca
Study Locations
-
-
Alberta
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Calgary, Alberta, Canada
- Recruiting
- University of Calgary
-
Contact:
- Meredith Brockway, RN PhD
- Phone Number: 4036890970
- Email: mbrockwa@ucalgary.ca
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Gestation up to 33 6/7 weeks at hospital admission (to guarantee at least 14 days intervention, since DHM fortification typically ends at 34+0 weeks adjusted gestational age).
- Provision of consent for infant to receive DHM.
- Mother has provided signed and dated informed consent and authorization to use protected health information, as required by national and local regulations.
- In the investigator's opinion, the subject mother understands and is able to comply with protocol requirements, instructions, and protocol-stated restrictions, and is likely to complete the study as planned.
Exclusion Criteria (Infant):
- Diagnosed with clinically significant major congenital malformation
- Intestinal perforation or stage 2 necrotizing enterocolitis (NEC)
- Unlikely to survive the study period
- Receiving extended courses of antibiotics (most infants are expected to receive up to 48hr antibiotic prophylaxis at birth according to standard NICU protocol; this criterion will only exclude infants receiving prolonged courses of antibiotics)
- Presence prior to enrollment of intestinal perforation or stage 2 necrotizing enterocolitis (NEC) prior to tolerating fortified feeds
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Matched donor human milk
Infants randomized to the matched donor human milk arm, will receive donor human milk which is matched to their mother's secretor status.
|
Milk from donor mothers will be sorted according to their secretor status.
This milk will be provided to infants in the intervention (experimental) arm.
|
No Intervention: Standard issue donor human milk
Infants randomized to the standard issue donor human milk arm, will receive donor human milk which is prepared without consideration of secretor status as per standard practice.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fecal microbiome composition
Time Frame: sampled weekly until infant transferred from level III NICU, they are no longer receiving donor human milk or up to 60 days, whichever comes first.
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16S RNA sequencing of fecal bacteria
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sampled weekly until infant transferred from level III NICU, they are no longer receiving donor human milk or up to 60 days, whichever comes first.
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Growth - weight
Time Frame: sampled weekly until infant transferred from level III NICU, they are no longer receiving donor human milk or up to 60 days, whichever comes first.
|
measured in grams
|
sampled weekly until infant transferred from level III NICU, they are no longer receiving donor human milk or up to 60 days, whichever comes first.
|
Growth - length
Time Frame: sampled weekly until infant transferred from level III NICU, they are no longer receiving donor human milk or up to 60 days, whichever comes first.
|
measured in centimetres
|
sampled weekly until infant transferred from level III NICU, they are no longer receiving donor human milk or up to 60 days, whichever comes first.
|
Growth - head circumference
Time Frame: sampled weekly until infant transferred from level III NICU, they are no longer receiving donor human milk or up to 60 days, whichever comes first.
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measured in centimetres
|
sampled weekly until infant transferred from level III NICU, they are no longer receiving donor human milk or up to 60 days, whichever comes first.
|
Days to full enteral feeds
Time Frame: Infant feeds are recorded daily, until infant transferred from level III NICU, they are no longer receiving donor human milk or up to 60 days, whichever comes first.
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Measure the number of days it takes from birth until the infant is taking 120 mL/kg/day (full feeds).
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Infant feeds are recorded daily, until infant transferred from level III NICU, they are no longer receiving donor human milk or up to 60 days, whichever comes first.
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Length of Stay
Time Frame: Measured when infant is discharged or transferred from unit, or up to 60 days, whichever comes first.
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Time, measured in days, from admission (birth) to discharge or 'step-down' to level II NICU
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Measured when infant is discharged or transferred from unit, or up to 60 days, whichever comes first.
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Donor human milk composition - human milk oligosaccharide concentrations
Time Frame: Sampled from milk donations to the milk bank, up to 52 weeks postpartum
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Individual human milk oligosaccharides concentrations - measured in mol/mL
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Sampled from milk donations to the milk bank, up to 52 weeks postpartum
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Donor human milk composition - nutritional composition
Time Frame: Sampled from milk donations to the milk bank, up to 52 weeks postpartum
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Micro-nutrients - measured in kcal/mL
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Sampled from milk donations to the milk bank, up to 52 weeks postpartum
|
Mothers own milk composition - Human milk oligosaccharide concentration
Time Frame: Sampled from one feeding of infant at 2 weeks post-birth.
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Human milk oligosaccharides concentrations - measured in mol/mL
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Sampled from one feeding of infant at 2 weeks post-birth.
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Mothers own milk - nutritional composition
Time Frame: Sampled from one feeding of infant at 2 weeks post-birth.
|
Micro-nutrients - measured in kcal/mL
|
Sampled from one feeding of infant at 2 weeks post-birth.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Meghan B Azad, PhD, University of Manitoba
Publications and helpful links
General Publications
- Marx C, Bridge R, Wolf AK, Rich W, Kim JH, Bode L. Human milk oligosaccharide composition differs between donor milk and mother's own milk in the NICU. J Hum Lact. 2014 Feb;30(1):54-61. doi: 10.1177/0890334413513923. Epub 2013 Nov 26.
- Lewis ZT, Totten SM, Smilowitz JT, Popovic M, Parker E, Lemay DG, Van Tassell ML, Miller MJ, Jin YS, German JB, Lebrilla CB, Mills DA. Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants. Microbiome. 2015 Apr 10;3:13. doi: 10.1186/s40168-015-0071-z. eCollection 2015.
- Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012 Sep;22(9):1147-62. doi: 10.1093/glycob/cws074. Epub 2012 Apr 18.
- Azad MB, Robertson B, Atakora F, Becker AB, Subbarao P, Moraes TJ, Mandhane PJ, Turvey SE, Lefebvre DL, Sears MR, Bode L. Human Milk Oligosaccharide Concentrations Are Associated with Multiple Fixed and Modifiable Maternal Characteristics, Environmental Factors, and Feeding Practices. J Nutr. 2018 Nov 1;148(11):1733-1742. doi: 10.1093/jn/nxy175.
- Parra-Llorca A, Gormaz M, Alcantara C, Cernada M, Nunez-Ramiro A, Vento M, Collado MC. Preterm Gut Microbiome Depending on Feeding Type: Significance of Donor Human Milk. Front Microbiol. 2018 Jun 27;9:1376. doi: 10.3389/fmicb.2018.01376. eCollection 2018.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- REB19-0542
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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