The Bloom Infant Probiotic (BIP) Study

Official title

A Randomised Controlled Trial to Assess if a Probiotic Intervention Leads to Enhanced Immune Responses to Vaccination in Antibiotic-treated Infants (Bloom Infant Probiotic (BIP) Study)

Overview

The goal of this clinical trial is to investigate whether administering a probiotic (Infloran®) to infants who received antibiotics in the first 28 days of life can restore or enhance their immune response to routine vaccines. Antibiotic use in the first weeks of life can lower the levels of beneficial gut bacteria, such as bifidobacteria, which play a key role in immune function. As a result, infants treated with antibiotics may produce fewer antibodies after routine vaccinations, leaving them less protected against infections. The main questions this study aims to answer are: * Does treatment with the probiotic Infloran® improve the geometric mean concentrations (GMCs) of anticapsular antibodies against at least 11 serotypes included in the pneumococcal conjugate vaccine (PCV20) in serum samples collected at 6 months of age compared with placebo in infants treated with antibiotics in the neonatal period? * Does treatment with the probiotic Infloran® improve the GMCs for the pneumococcal conjugate vaccine (PCV20) at 12 months of age compared with placebo in infants treated with antibiotics in the neonatal period? * Does treatment with the probiotic Infloran® improve the GMCs of other routine childhood vaccines at 6 and 12 months of age compared with placebo in infants treated with antibiotics in the neonatal period? * Does treatment with the probiotic Infloran® increase the proportion of infants achieving seroprotective antibody levels for pneumococcal antigens compared to placebo in infants treated with antibiotics in the neonatal period? * What are the differences in antigen specific T cell responses, flow cytometry, blood transcriptomics, and gut microbiota composition in the probiotic (Infloran®) vs placebo groups in infants treated with antibiotics in the neonatal period? Researchers will compare infants who receive Infloran® (a probiotic containing Bifidobacterium bifidum and Lactobacillus acidphilus) with those who receive a placebo (which contains the same excipients as Infloran® but does not contain any bacterial strains). Participants will: * Be randomly assigned to receive either a 14-day course of probiotic Infloran® or a placebo. * Provide blood samples (3-5 mL) at 6 weeks, 6.5 weeks (optional blood-draw for exploratory endpoint), 6 months and 12 months of age. * Provide stool samples at four timepoints: prior to starting the intervention (probiotic/placebo), on day 7, on day 14 after completion of the study supplement, and prior to their first vaccination at 6 weeks of age. * Receive routine vaccinations at 6 weeks, 4 months and 6 months in line with the National Immunisation Program * Complete surveys to collect information regarding probiotic/placebo administration and vaccination related side effects This study aims to recruit 360 infants to assess whether this probiotic treatment following antibiotic exposure improves the immunogenicity of vaccinations. The information from this study will improve our understanding of how probiotic intervention can support optimal immune responses to vaccination in early life. The findings could potentially influence public health strategies, offering a new way to support optimal vaccine responses in antibiotic-treated infants.

Interventions

• Drug Probiotic
  Probiotic capsule contents will be dissolved in a small amount of breast milk, formula or sterile water (drinking water boiled, then cooled) and administered by the infant's parent/guardian to infants as an oral bolus dose. Probiotic Infloran® Hard capsules (Bifidobacterium bifidum \& Lactobacillus acidophilus) are a listed medicine on the Australian Register of Therapeutic Goods (ARTG). Infloran® has been previously used in infants including pre-term infants for other indications including supp
• Drug Matching placebo
  Placebo contains the same excipients as Infloran, it is also made from the same capsule, but it does not contain any bacterial strains. Placebo capsule contents will be dissolved in a small amount of breast milk, formula or sterile water (drinking water boiled, then cooled) and administered by the infant's parent/guardian to infants as an oral bolus dose. The placebo is manufactured by Syntro Health, 558-562 Swan St, Richmond, VIC 3121.

Primary outcome measures

• The Geometric Mean Concentrations (GMCs) of anticapsular antibodies against at least 11 serotypes included in the pneumococcal conjugate vaccine (PCV20) in serum collected at 6 months in the probiotics vs placebo group. [Time frame: 6 months]

Secondary outcome measures (3)

• The GMCs for at least 11 serotypes included in pneumococcal conjugate vaccine (PCV20) as measured by serum assay at 12 months in the probiotic vs. placebo group. [Time frame: 12 months]
• The GMCs for other vaccine antigens (e.g. diphtheria, tetanus and pertussis toxoids, Haemophilus influenzae type b polyribosylribitol phosphate, Hepatitis B surface antigen) as measured by serum assays at 6 and 12 months in both arms. [Time frame: 12 months]
• Proportion of infants achieving seroprotective antibody levels (i.e. seroprotection) for pneumococcal antigens. [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Infants administered antibiotics in the first 28 days of life. Infants must have documented direct antibiotic exposure - defined as having received at least 36 hours of antibiotic treatment in the neonatal period (the first 28 days after birth).
• Gestational age ≥ 35 weeks.
• Birth weight ≥ 2500g.
• Mother aged at least 18 years and able and willing to provide written informed consent for themselves and their infant.
• Parent/guardian agrees to not give any other probiotics to their infant prior to vaccination at 6 weeks, including any formula that contains probiotics.
• Infant planning to receive all nationally approved vaccines during next 6 months.

Exclusion criteria

• Significant medical condition in either the mother or infant that, in the opinion of a medical investigator, may interfere with the study.
• Infant had confirmed sepsis or other serious infection in the neonatal period.
• Infants with known congenital diseases or who are immunocompromised or considered medically at risk (MAR).
• Infant participating in another interventional trial during the trial period.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Australia · 2 centers

• Women's and Children's Hospital, Adelaide — Adelaide
• Flinders Medical Centre — Adelaide

Identifiers

NCT: NCT07189390 · 2025/HRE00173

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗