Matching Donor Human Milk On Maternal Secretor Status (MMOMSS) Study

NCT ID: NCT04130165

Last Updated: 2024-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-29

Study Completion Date

2025-12-31

Brief Summary

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This study will evaluate the impact of matching donor human milk to the maternal secretor status of very preterm infants (\<34 weeks gestation) on the gut microbiome. Half of enrolled infants will receive donor human milk which is matched their mother's secretor status and half will receive standard (unmatched) donor human milk, which is standard care in the neonatal intensive care unit.

Detailed Description

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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.

Conditions

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Microbial Colonization Preterm Birth

Keywords

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preterm infants human milk microbiome donor human milk breastmilk

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Pilot Randomized Control Trial
Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors
Outcome assessor (lab technician/research assistant) will not be aware of the group allocation or nutritional intake of the infant while completing data analysis.

We cannot blind participants or care providers as provision of matched donor human milk will require preparation which deviates from standard protocol, and the bedside nurse will need to conduct this preparation.

Study Groups

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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.

Group Type EXPERIMENTAL

Matched donor human milk

Intervention Type OTHER

Milk from donor mothers will be sorted according to their secretor status. This milk will be provided to infants in the intervention (experimental) arm.

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Matched donor human milk

Milk from donor mothers will be sorted according to their secretor status. This milk will be provided to infants in the intervention (experimental) arm.

Intervention Type OTHER

Eligibility Criteria

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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

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Calgary

OTHER

Sponsor Role collaborator

University of Manitoba

OTHER

Sponsor Role lead

Responsible Party

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Meghan Azad

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Meghan B Azad, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Manitoba

Locations

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University of Calgary

Calgary, Alberta, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type BACKGROUND
PMID: 30247646 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22513036 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24282194 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29997594 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25922665 (View on PubMed)

Related Links

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Other Identifiers

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REB19-0542

Identifier Type: -

Identifier Source: org_study_id