Activation of NOD2 Receptors in Preterm Infants by Lactobacillus Reuteri DSM17938 (NOD2-Pilot)

A Pilot Study on the Activation of NOD2 Receptors in Preterm Infants by Lactobacillus Reuteri DSM17938

Primary Objective: To evaluate the capacity of Lactobacillus reuteri DSM17938 to activate NOD2 receptors in preterm infants.

Secondary Objective: To analyze the impact of Lactobacillus reuteri DSM17938 on the gut microbiome of preterm infants

Study Overview

• Status: Completed
• Conditions: Preterm Infants
• Intervention / Treatment: Other: DSM17938+Routine clinical treatment

Detailed Description

This study was designed as an open-label, stratified, randomized, parallel-controlled pilot study, using gestational age as the stratification factor. Participants were stratified according to birth gestational age < 32 weeks, 32 weeks ≤ birth gestational age < 37 weeks, and simple randomization method was used in each gestational age group. All subjects were enrolled after birth/hospital admission, and the experimental group started intervention at 10-14 days after birth, and the intervention period was 14 days.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital, Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Preterm infants with a gestational age of less than 37 weeks.
2. Birth weight of less than 2500 grams.
3. Hospitalized within 72 hours after birth.
4. Parents or legal guardians have signed an informed consent form.

Exclusion Criteria:

1. Congenital digestive tract malformations, genetic metabolic diseases, or congenital immunodeficiency diseases.
2. A history of severe asphyxia, infection, or liver and kidney dysfunction at birth/enrollment.
3. Death within 72 hours after birth.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DSM17938+Routine clinical treatment; Lactobacillus reuteri DSM17938，5 drops per day by mouth (containing at least 100 million CFU of Lactobacillus reuteri DSM17938)	Other: DSM17938+Routine clinical treatment; Lactobacillus reuteri DSM17938，5 drops per day by mouth (containing at least 100 million CFU of Lactobacillus reuteri DSM17938)，Routine clinical treatment
No Intervention: Routine clinical treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of NOD2 ligand in fecal samples	The supernatants of fecal samples were used to examine the content of NOD2 ligand with the human NOD2/NF-κB/secreted embryonic alkaline phosphatase (SEAP) reporter HEK293 cell	Pre-intervention Phase: On the 3rd day after birth (V1), 7th day (V2), and 10th day (V3). Intervention Phase: During the intervention period, on the 2nd day (V4), 4th day (V5), 6th day (V6), 8th day (V7), 10th day (V8), 12th day (V9), and 14th day (V10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative Abundance of Operational Taxonomic Units (OTUs) in Fecal Samples	DNA extraction was performed using the QIAamp Mini Kit following the manufacturer's instructions. The V4 hypervariable region of the 16S ribosomal RNA (rRNA) gene was amplified and sequenced on an Illumina ISEQ 100 platform, generating 250 bp paired-end reads. Raw sequencing data quality was assessed and controlled using fastp (v0.23.2). Adapter sequences corresponding to the V3-V4 region were removed with cutadapt. Amplicon sequence variants (ASVs) were identified by denoising the paired-end FASTQ files with DADA2 (v1.6.0) in R. Representative sequences were aligned using the PyNAST algorithm (v1.2.2), and a phylogenetic tree was constructed with FastTree (v2.1.3). Taxonomic classification of ASVs was performed using the Ribosomal Database Project (RDP) classifier against the Greengenes database. To minimize biases from variations in sequencing depth, all samples were rarefied before downstream analyses.	Pre-intervention Phase: On the 3rd day after birth (V1), 7th day (V2), and 10th day (V3). Intervention Phase: During the intervention period, on the 2nd day (V4), 4th day (V5), 6th day (V6), 8th day (V7), 10th day (V8), 12th day (V9), and 14th day (V10)
Concentration of DSM17938 per Gram of Feces Quantified by qPCR	Quantitative fluorescence PCR (qPCR) was used to detect DSM17938	Pre-intervention Phase: On the 3rd day after birth (V1), 7th day (V2), and 10th day (V3). Intervention Phase: During the intervention period, on the 2nd day (V4), 4th day (V5), 6th day (V6), 8th day (V7), 10th day (V8), 12th day (V9), and 14th day (V10)

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University
• Investigators: Study Chair: Wei Shen, Doctor, Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2024
• Primary Completion (Actual): January 19, 2025
• Study Completion (Actual): January 19, 2025

Study Registration Dates

• First Submitted: December 24, 2024
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 19, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: preterm infant; DSM17938; NOD2
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth
• Other Study ID Numbers: NFEC-2024-654

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The following study documentation will be made available for sharing: study protocol, statistical analysis plan, informed consent form, clinical study report, and analytic code.
• IPD Sharing Time Frame: The study data will be accessible for sharing during a specified temporal window, initiating three months after study completion and publication, with availability extending through a two-year period post-publication.
• IPD Sharing Access Criteria: Data can be shared with researchers for scientific purposes upon application to the corresponding author. The research institution's ethics committee and data safety committee will review such requests. Data sharing will be permitted only following committee approval and after proper de-identification of patient information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No