PrePhage - Faecal Bacteriophage Transfer for Enhanced Gastrointestinal Tract Maturation in Preterm Infants

Official title

PrePhage - Faecal Bacteriophage Transfer for Enhanced Gastrointestinal Tract Maturation in Preterm Infants - Clinical Trial

Overview

PrePhage - Fecal bacteriophage transfer for enhanced gastrointestinal tract maturation in preterm infants This pilot triol has the primary goal of demonstrating the safety of transferring viruses and proteins from healthy term infants to preterm infants born between gestational age (GA) 26 + 0 and 30+6. The long-term goal is to develop a safe and effective treatment to prevent the severe gut disease called necrotizing enterocolitis (NEC). NEC is a common disease in neonatal intensive care units affecting 5-10% of all admitted patients. 15-30% of the affected children die from the disease, and many of the survivors suffer from the effects of extensive gut surgery. While the disease is caused by many different factors, recent research has shown the gut microbiome to be a central factor in the development of NEC. Furthermore, in the recent years special viruses called bacteriophages have shown potential in the treatment of various diseases. By collecting feces from healthy, term infants and filtering it thoroughly, the investigators can provide a treatment that contains practically only viruses, proteins and nutrients. It is our belief that giving the preterm infants a mix of viruses including bacteriophages will prevent NEC. To do this, the investigators will go through 3 stages: 1. Recruiting and following healthy donor infants to study the microbiota and use feces from them to donate in stage 2 and 3 2. Examining the safety of the treatment as well as how it works in preterm piglets 3. Testing the treatment in preterm infants. 10 preterm infants will receive the treatment and 10 preterm infants will receive placebo. The investigators expect to see no serious side effects to the treatment. The investigators hope, but do not expect to be able to see a beneficial effect of the treatment. If this pilot trial shows promising results, it will be followed be a larger clinical trial.

Detailed description

PrePhage - Fecal bacteriophage transfer for enhanced gastrointestinal tract maturation in preterm infants

This pilot trial aims to investigate if fecal filtrate transfers (FFT) to preterm infants is safe and tolerable. To investigate this, the investigators will recruit 20 donor infants and their mothers from time of delivery, and both will be subjected to a novel screening program including blood, urine, breastmilk, fecal screening and standard clinical investigation. Donor fecal samples will be collected from time of birth and with varying intervals for consecutive 3 years for 3 purposes: 1) to conduct safety studies in preterm piglets before transfer to preterm recipient infants, 2) to conduct FFT to preterm infants, and 3) to map normal microbiota development in healthy infants. The feces used for donation will be collected between 2-4 weeks after birth. After 1 year, donated feces will be released for FFT to preterm, but only if the donor infant at this time has been healthy and normally developed. Donors are followed up for consecutive 3 years after birth. Maternal fecal samples will be compared to infant samples, to investigate maternal to infant transfer of microbiota, as well as changes in infant microbiota in response to environment.

20 preterm infants with gestational age between 26 +0 - 30+6 weeks + days, are block randomized to either FFT or saline placebo within 24 hours after birth and the following 3 days, in total 4 donations. The recipients are clinically and biochemically closely monitored by attending staff and the group of investigators according to best clinical practice and predefined clinical observation. The recipients are followed up for consecutive 3 years to evaluate potential late side-effects and to monitor change in fecal microbiome after transplant or placebo.

The primary endpoint is to assess safety of FFT to preterm infants with expected no increase in necrotizing enterocolitis (NEC), sepsis and death in the intervention group. The secondary endpoint is to assess if, FFT treatment will reduce incidence of feeding tolerance and improve healthy gut development in recipient preterm infants. The investigators expect to find FFT safe and with fewer cases of NEC and sepsis. The investigators do not expect to prove the effect of the intervention in this study. However, the investigators aim to follow up with a double-blinded multicenter randomized control trial - powered to document our hypothesis - that when colonizing with a healthy microbiome, it is possible decrease incidence of NEC in premature infants.

Interventions

• Other Fecal Filtrate Transfer
  Treatment with donated fecal samples filtered to contain practically no bacteria and mainly viruses, including bacteriophages
• Other Placebo
  Saline solution

Primary outcome measures

• No serious adverse events [Time frame: 14 days]

Secondary outcome measures (12)

• Feeding tolerance [Time frame: 1 month]
• Microbiota Composition [Time frame: 1 month]
• Time to full enteral feeding [Time frame: 1 month]
• Blood pressure [Time frame: 1 month]
• Temperature [Time frame: 1 month]
• Pulse [Time frame: 1 month]
• Length [Time frame: 1 month]
• Weight [Time frame: 1 month]
• Stool characteristics - Amount [Time frame: 1 month]
• Stool characteristics - Consistency [Time frame: 1 month]
• Stool characteristics - Color [Time frame: 1 month]
• Days of hospitalization [Time frame: 1 month]

Eligibility criteria

Inclusion criteria for participant preterm infants

• Preterm infants born between GA 26+0 and 30+6
• Delivery at RH or transferred to RH NICU within 24 hours of delivery
• Children administered prophylactic antibiotics due to maternal risk factors, specifically: premature rupture of membranes, groub b streptococcus positive, feber during labour
• Signed parental consent

Exclusion criteria for participant preterm infants

• Major congenital anomalies or birth defects
• Antibiotics for more than 72 hours after birthExtremely SGA infant (weight SD score < -3 SD)
• Need for mechanical ventilation or cardiovascular support before first FFT treatment

Inclusion criteria for mothers of participants

• Women aged 18-45
• Ability to give informed consent

Exclusion criteria for participant mothers

● Mothers who have severe infection, defined by need for other treatment to support infection-related comorbidities, besides from antibiotics (e.g. inotropic treatment, iv fluid resuscitation)

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Denmark · 1 center

• Rigshospitalet — Copenhagen

Publications

• Kappel SS, Jakobsen GR, Oestergaard KL, Brunse A, Nielsen DS, Aunsholt L. Parental Consent to a Neonatal Clinical Study: The Roles of Uncertainty, Burden of Sample Collection and Societal Expectations. Acta Paediatr. 2026 Feb;115(2):353-359. doi: 10.1111/apa.70333. Epub 2025 Oct 6. PMID 41051016

Identifiers

NCT: NCT05272579 · Rigshospitalet - PrePhage

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗