Influence of Intestinal Microbiota Implantation in Preterm Infants on Microbiota and Immune Orientation at 3 Years

Infant, Premature Clinical Trial

— PrimiBiota  

Official title:

Influence of Intestinal Microbiota Implantation Parameters in the Neonatal Period in Premature Infants on Microbiota Profiles and Immune Orientation at 3 Years of Age

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02738411
• Other study ID #: PHRC-I/2015/AF-01
• Status: Active, not recruiting
• Start date: May 12, 2017
• Est. completion date: June 30, 2024

Study information

• Verified date: February 2024
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The main objective of this research is to study the links between changes in the intestinal microbiota (in terms of diversity) during the first 6 weeks of life for preterm infants and the presence / absence of a TH1 immune status at 36 months of age.

Description:

The secondary objectives are to study the links between changes of the intestinal microbiota premature infants in terms of:

• changing diversity of the microbiota in the first 6 weeks of life;

• changes in the bacterial community (UniFrac study) during the first 6 weeks of life;

• diversity of the microbiota up to 6 weeks;

-AND-

• diversity of the microbiota at 1, 2 & 3 years;

• bacterial communities (UniFrac study) at 1, 2 & 3 years;

• lymphocyte subpopulation profiles at 3 years;

• serum immunoglobulin A, G, M, E levels at 3 years;

• history of infectious episodes, allergic and inflammatory episodes during the first 3 years of life.

The links between certain variables known in the literature and neonatal microbiota will be confirmed / studied in our population:

• mode of delivery;

• length (and type) of antibiotic therapy in the neonatal period;

• duration of breastfeeding.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: June 30, 2024
• Est. primary completion date: November 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 1 Day

Eligibility

Inclusion Criteria:

• The parents of the patient (or legal guardian if any) have been informed about the implementation of the study, its objectives, its constraints, and patient rights

• The parents of the patient (or legal guardian if any) must have given their free and informed consent and signed the consent form

• The patient must be affiliated with or beneficiary of a health insurance plan

• Premature infants born at less than 33 weeks of gestation

Exclusion Criteria:

• The patient is participating in another interventional study (Excepted " Recherche du Portage de Clostridium butyricum et de Toxines de Clostridium chez les Prématurés Hospitalisés en Néonatologie afin de prédire la survenue d'Entérocolites Nécrosantes", RCB 2016-A00-529-42 ; " BetaDose Dose reduction of antenatal betamethasone given to prevent the neonatal complications associated with very preterm birth ", RCB 2016-001486-90.

• It is not possible to correctly inform the parent (or legal guardian, if applicable)

• A serious deformity or digestive malformation was diagnosed at birth

• During the hospital stay in the neonatology department, the patient had a digestive disease requiring surgery (except necrotizing enterocolitis)

• A transfer to another hospital is foreseen/predictable (eg, due to geographical distance)

Related Conditions & MeSH terms

• Infant, Premature
• Premature Birth

Locations

Country	Name	City	State
France	CHRU de Montpellier - Hôpital Arnaud de Villeneuve	Montpellier
France	CHRU de Nîmes - Hôpital Universitaire Carémeau	Nîmes Cedex 09
France	Réseau GRANDIR EN LANGUEDOC-ROUSILLON	Saint Gely Du Fesc

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum Immunoglobulin A level		36 months
Other	Serum Immunoglobulin G level		36 months
Other	Serum Immunoglobulin M level		36 months
Other	Serum Immunoglobulin E level		36 months
Other	The number of days in good health and no medications		36 months
Other	Richness of fecal microbiota (number of operational taxonomic units observed)		Day 0 (first meconium)
Other	Richness of fecal microbiota (number of operational taxonomic units observed)		Week 1
Other	Richness of fecal microbiota (number of operational taxonomic units observed)		Week 2
Other	Richness of fecal microbiota (number of operational taxonomic units observed)		Week 3
Other	Richness of fecal microbiota (number of operational taxonomic units observed)		Week 4
Other	Richness of fecal microbiota (number of operational taxonomic units observed)		Week 5
Other	Richness of fecal microbiota (number of operational taxonomic units observed)		Week 6
Other	Richness of fecal microbiota (number of operational taxonomic units observed)		12 months
Other	Richness of fecal microbiota (number of operational taxonomic units observed)		24 months
Other	Richness of fecal microbiota (number of operational taxonomic units observed)		36 months
Other	Diversity of fecal microbiota (Shannon's index)		Day 0 (first meconium)
Other	Diversity of fecal microbiota (Shannon's index)		Week 1
Other	Diversity of fecal microbiota (Shannon's index)		Week 2
Other	Diversity of fecal microbiota (Shannon's index)		Week 3
Other	Diversity of fecal microbiota (Shannon's index)		Week 4
Other	Diversity of fecal microbiota (Shannon's index)		Week 5
Other	Diversity of fecal microbiota (Shannon's index)		Week 6
Other	Diversity of fecal microbiota (Shannon's index)		12 months
Other	Diversity of fecal microbiota (Shannon's index)		24 months
Other	Diversity of fecal microbiota (Shannon's index)		36 months
Other	Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Day 0 (first meconium)
Other	Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 1
Other	Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 2
Other	Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 3
Other	Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 4
Other	Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 5
Other	Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 6
Other	Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	12 months
Other	Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	24 months
Other	Functional richness of fecal microbiota (number of functional groups observed)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	36 months
Other	Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Day 0 (first meconium)
Other	Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 1
Other	Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 2
Other	Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 3
Other	Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 4
Other	Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 5
Other	Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	Week 6
Other	Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	12 months
Other	Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	24 months
Other	Functional diversity of fecal microbiota (Shannon's index)	Functional groups are determined via the classification of each OTU according to the following factors: 1) pathogenicity (pathogen/intermediate/commensal); 2) aerobic versus anaerobic; 3) Cocci + versus others.	36 months
Other	The relative abundance of primary fecal microbiota families		Day 0 (first meconium)
Other	The relative abundance of primary fecal microbiota families		Week 1
Other	The relative abundance of primary fecal microbiota families		Week 2
Other	The relative abundance of primary fecal microbiota families		Week 3
Other	The relative abundance of primary fecal microbiota families		Week 4
Other	The relative abundance of primary fecal microbiota families		Week 5
Other	The relative abundance of primary fecal microbiota families		Week 6
Other	The relative abundance of primary fecal microbiota families		12 months
Other	The relative abundance of primary fecal microbiota families		24 months
Other	The relative abundance of primary fecal microbiota families		36 months
Other	Fecal microbiota unifrac ordination score		Day 0 (first meconium)
Other	Fecal microbiota unifrac ordination score		Week 1
Other	Fecal microbiota unifrac ordination score		Week 2
Other	Fecal microbiota unifrac ordination score		Week 3
Other	Fecal microbiota unifrac ordination score		Week 4
Other	Fecal microbiota unifrac ordination score		Week 5
Other	Fecal microbiota unifrac ordination score		Week 6
Other	Fecal microbiota unifrac ordination score		12 months
Other	Fecal microbiota unifrac ordination score		24 months
Other	Fecal microbiota unifrac ordination score		36 months
Primary	The presence/absence of a Th1 type immune orientation	Immune orientation will be determined according to the following ratio determined by lymphocyte stimulation tests: INF-gamma/(INF-gamma+IL+4). The latter ratio varies between 0 and 0.5 with IL-4 > INF-gamma (TH2 orientation) and between 0.5 and 1 when INF-gamma > IL-4 (TH1 orientation).	36 months
Secondary	Blood lymphocyte subset determination	Subsets are determined according to the presence/absence of the following differentiation clusters: CD3, CD4, CD8, CD19, CD25, CD56, CD127, FOXP3.	36 months