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

Gut Microbiota Clinical Trial

Official title:

Targeting Gut Microbiota and Metabolites for Very Preterm Infants Through Oropharyngeal Administration of Colostrum: Protocol for a Multicenter Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05481866
• Other study ID #: SZPH-2022-52
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 2022
• Est. completion date: October 2023

Study information

• Verified date: July 2022
• Source: Shenzhen People's Hospital
• Contact: Zhangbin Yu, PhD
• Phone: 13913994149
• Email: yuzhangbin[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Preterm infants with gestational age < 32 weeks and weight < 1500g will be evaluated. Infants who met the inclusion criteria will be randomly divided into two groups according to the ratio of 1:1. The intervention group will be given oropharyngeal colostrum every 3 hours for 5 days; the control group will be given sterile water with the same dosage and administration scheme. Stool samples will be collected at the first defecation and the 7th day to detect the gut microbiota and metabolites.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 320
• Est. completion date: October 2023
• Est. primary completion date: October 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 32 Weeks

Eligibility

Inclusion criteria:

• 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.

Exclusion criteria:

• 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).

Related Conditions & MeSH terms

• Gut Microbiota
• Metabolites

Intervention

Other:
• Oropharyngeal administration of colostrum
The intervention group will be given 0.2ml colostrum for oropharyngeal administration every 3 hours.
• Oropharyngeal administration of sterile water
The control group will be given 0.2ml sterile water for oropharyngeal administration every 3 hours.

Locations

Country	Name	City	State
China	Shenzhen People's Hospital	Shenzhen	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Shenzhen People's Hospital	Longgang Maternal and Child Health Hospital, Shenzhen, Guangdong, Shenzhen Bao'an Maternal and Child Health Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	A between-group difference in the Simpson diversity index at the 7th day	Simpson diversity index explains species richness, which is one of the alpha diversity indexes and susceptible to rare species.	1 year
Secondary	A between-group difference in the Chao1 diversity index at the 7th day.	Chao1 diversity index explains species richness, which is one of the alpha diversity indexes.	1 year
Secondary	Proportion of gut microbiota (phylum and genus level)at the 7th day.	After preprocessing to remove low-quality sequences, the original data will be analyzed according to the steps of 16S rRNA discovery, clustering and identification. Calculate the number of operational taxonomic units (OTUs) of each sample at a 97% sequence similarity level. A specific taxonomic units represents a specific species.	1 year
Secondary	Gut microbial beta diversity explaining between-sample dissimilarity will be calculated using the Vegan package.	Adonis permutational multivariate analysis of variance of Bray-Curtis distances with 9999 permutations will be used to compare the microbial community structure between each of the two groups at the 7th day.	1 year
Secondary	Correlation between dominant microbiota and metabolites	The correlation between the relative abundance of dominant bacterial taxa from 16S rRNA gene sequencing and the intensity of metabolites of interest will be determined by sparse partial least squares regression (SPLs) at the first defecation at the 7th day.	1 year