Prephage - Faecal Bacteriophage Transfer for Enhanced Gastrointestinal Tract Maturation in Preterm Infants - Donor Study

NCT ID: NCT05272566

Last Updated: 2024-06-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 38 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-04-01
• Study Completion Date: 2024-03-20

Brief Summary

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:

Recruiting and following healthy donor infants to study the microbiota and use feces from them to donate in stage 2 and 3 Examining the safety of the treatment as well as how it works in preterm piglets

STAGE 3 will be performed only if stage 2 shows no serious risks for the infants

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

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.

Conditions

Feeding Patterns; Microbial Colonization

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Infants

30 healthy, term infants are recruited for 2 purposes:

1. To study the development of gut bacteria and viruses over time

2. To use as donors in a separate trial

No interventions assigned to this group

Mothers

30 healthy pregnant women are recruited along with their infants

1. To compare gut bacteria and viruses with those of their children

2. To screen for disease transferrable by breastfeeding

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• The donor must be of term (>37+0 weeks GA, < 41+0 weeks GA),
• Be born vaginally with no maternal pre-birth infection,
• Be exclusively breastfed un till fulfilled donation at 4 weeks of age,
• Have no known predisposition for disease.

• Women aged 18-45 and currently healthy
• No continuous medical consumption with effects on microbiome
• Non-smoking
• Ability to give informed consent

Exclusion Criteria

• Antibiotic exposure before collection of faecal material for donation,
• Disease between time of birth and collection of feces for donation,
• Major congenital anomalies or birth defects, perinatal asphyxia, need for mechanical ventilation or cardiovascular support before time of inclusion.
• Positive stool sample for C. difficile toxin, parasites or other pathogens
• Positive HIV, HBV, or HCV or CMV
• Parents who do not want to know the HIV, HBV or HCV status of the child

• Known or high risk of infectious disease such as HIV, HBV, or HCV
• Positive CMV IgM during pregnancy
• Positive stool sample for C. difficile toxin, parasites or other pathogens
• Systemic antibiotic treatment < 1 months prior to study
• New tattoo < 1 month prior to study
• Risky sexual behavior
• Gestational diabetes
• Family history of inflammatory bowel disease

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Lise Aunsholt, Neonatologist, Clinical Professor

UNKNOWN

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Gustav Riemer Jakobsen

Medical Doctor, Ph.d-student

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lise Aunsholt, md, phd

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Locations

Gustav R Jakobsen

Copenhagen, , Denmark

Countries

Denmark

References

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. 2025 Oct 6. doi: 10.1111/apa.70333. Online ahead of print.

Reference Type: DERIVED

PMID: 41051016 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PrePhage, Donor

Identifier Type: -

Identifier Source: org_study_id