Clinical trial NCT05481866: Targeting Gut Microbiota and Metabolites for Very Preterm Infants Through Oropharyngeal Administration of Colostrum
Official title: Targeting Gut Microbiota and Metabolites for Very Preterm Infants Through Oropharyngeal Administration of Colostrum: Protocol for a Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Gut Microbiota
Metabolites
Lead sponsor: Shenzhen People's Hospital
Sponsor class: OTHER
Collaborators: name: Shenzhen Bao'an Maternal and Child Health Hospital
name: Longgang Maternal and Child Health Hospital, Shenzhen, Guangdong
First posted: 2022-08-01
Enrollment: 320
Sex: ALL
Maximum age (years): 32
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: A between-group difference in gut microbial alpha diversity will be measured by Shannon diversity index at the 7th day.
timeFrame: 1 year
measure: 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.
timeFrame: 1 year
Secondary outcomes:
measure: A between-group difference in the Simpson diversity index at the 7th day
timeFrame: 1 year
measure: A between-group difference in the Chao1 diversity index at the 7th day.
timeFrame: 1 year
measure: Proportion of gut microbiota (phylum and genus level）at the 7th day.
timeFrame: 1 year
measure: Gut microbial beta diversity explaining between-sample dissimilarity will be calculated using the Vegan package.
timeFrame: 1 year
measure: Correlation between dominant microbiota and metabolites
timeFrame: 1 year
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
Study officials:
affiliation: Shenzhen People's Hospital
name: Zhangbin Yu, PhD
role: PRINCIPAL_INVESTIGATOR
References: