Targeting Gut Microbiota and Metabolites for Very Preterm Infants Through Oropharyngeal Administration of Colostrum

NCT05481866 | Unknown DMC

• 1 other identifier: SZPH-2022-52
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Oropharyngeal administration of colostrum (OAC) has an immune stimulating effect on oropharyngeal-associated lymphoid tissue, and can also promote the maturation of the gastrointestinal tract. However, how OAC promotes intestinal maturation in preterm infants by altering the gut microbiota remains unclear. We aim to assess the changes of gut microbiota and metabolites after OAC in very preterm infants. Methods: A multicenter, double-blind, randomized controlled trial will be conducted in 3 large NICUs in Shenzhen, China, for preterm infants with gestational age less than 32 weeks and birth weight less than 1500g. The intervention group will be given 0.2ml colostrum for oropharyngeal administration every 3 hours, which will start between the first 48 to 72 hours and continue for 5 consecutive days; The control group will be given sterile water for oropharyngeal administration, and the administration scheme will be the same as above. Stool samples will be collected at the first defecation and the 7th day after birth. It is estimated that 320 preterm infants will participate in the study within 1 year. 16sRNA gene sequencing and liquid chromatography-mass spectrometry will be used to analyze the effect of OAC on gut microbiota and metabolites. Discussion: The proposal advocates for the promotion of OAC as a safe and relatively beneficial initiative among neonatal intensive care units, and this initiative may contribute to the establishment of a dominant intestinal flora. Findings of this study may help to improve the health outcomes of preterm infants by constructing targeted gut microbiota in future studies.

Conditions

Gut Microbiota; Metabolites

Outcome Measures

Primary Outcomes (2)

• A between-group difference in gut microbial alpha diversity will be measured by Shannon diversity index at the 7th day.

  Shannon diversity Index explains species richness and evenness, which is one of the alpha diversity indexes and less affected by rare species.

  1 year

• Between-group differences in the concentration of fecal metabolites (short chain fatty acids) will be quantitatively measured by non targeted liquid chromatography-mass spectrometry (LC-MS) at the 7th day.

  Non-targeted LC-MS will be used to evaluate short chain fatty acids and other organic acids and alcohols. The relative and absolute quantitative results of metabolites will be calculated by fold change (FC) value, and the difference of metabolite expression between the two groups will be explored.

  1 year

Secondary Outcomes (5)

• A between-group difference in the Simpson diversity index at the 7th day

  1 year

• A between-group difference in the Chao1 diversity index at the 7th day.

  1 year

• Proportion of gut microbiota (phylum and genus level）at the 7th day.

  1 year

• Gut microbial beta diversity explaining between-sample dissimilarity will be calculated using the Vegan package.

  1 year

• Correlation between dominant microbiota and metabolites

  1 year

Study Arms (2)

The intervention group will be given colostrum for oropharyngeal administration

EXPERIMENTAL

The intervention group will be given 0.2ml colostrum for oropharyngeal administration every 3 hours, which will start between the first 48 to 72 hours and continue for 5 consecutive days.

Other: Oropharyngeal administration of colostrum

The control group will be given sterile water for oropharyngeal administration

PLACEBO COMPARATOR

The control group will be given sterile water for oropharyngeal administration, and the administration scheme will be the same as above.

Other: Oropharyngeal administration of sterile water

Interventions

Oropharyngeal administration of colostrum OTHER

The intervention group will be given 0.2ml colostrum for oropharyngeal administration every 3 hours.

The intervention group will be given colostrum for oropharyngeal administration

Oropharyngeal administration of sterile water OTHER

The control group will be given 0.2ml sterile water for oropharyngeal administration every 3 hours.

The control group will be given sterile water for oropharyngeal administration

Eligibility Criteria

• Age: Up to 32 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• gestational age less than 32 weeks and birth weight less than 1500g;
• admission to NICU ≤ 24 hours;
• be able to start the agreement within 72 hours of birth.

You may not qualify if:

• birth asphyxia (defined as umbilical artery / first hour arterial PH \< 7.0 or cardiopulmonary resuscitation in the delivery room);
• birth complicated with severe gastrointestinal malformations (such as intestinal atresia, esophago-tracheal fistula, intestinal rotation abnormalities, congenital megacolon);
• prenatal diagnosis of congenital chromosomal abnormalities or suspected congenital genetic metabolic diseases;
• maternal drug abuse or contraindications to breastfeeding (HIV and cytomegalovirus infection).

Sponsors & Collaborators

• Shenzhen People's Hospital: lead
• Shenzhen Bao'an Maternal and Child Health Hospital: collaborator
• Longgang Maternal and Child Health Hospital, Shenzhen, Guangdong: collaborator

Study Sites (1)

Shenzhen People's Hospital

Shenzhen, Guangdong, China

Location

Related Publications (1)

• Wang N, Zhang J, Yu Z, Yan X, Zhang L, Peng H, Chen C, Li R. Oropharyngeal administration of colostrum targeting gut microbiota and metabolites in very preterm infants: protocol for a multicenter randomized controlled trial. BMC Pediatr. 2023 Oct 16;23(1):508. doi: 10.1186/s12887-023-04346-x.

  PMID: 37845612 DERIVED

Study Officials

• Zhangbin Yu, PhD

  Shenzhen People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhangbin Yu, PhD

CONTACT

13913994149; yuzhangbin@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: August 1, 2022
• Study Start: October 1, 2022
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: August 2, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)