Necrotizing EnterocolitisEarly Phase 1NCT05272579
PrePhage - Faecal Bacteriophage Transfer for Enhanced Gastrointestinal Tract Maturation in Preterm Infants
A Early Phase 1 study testing Fecal Filtrate Transfer in people with Necrotizing Enterocolitis and Microbial Substitution, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Necrotizing Enterocolitis, Microbial Substitution
- What is being tested?
- Fecal Filtrate Transfer
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- 7 Nov 2023to 31 Dec 2025
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
- Women aged 18-45
- Ability to give informed consent
Who cannot join
- 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
- ● 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Rigshospitalet
Copenhagen, 2100
Gustav R Jakobsen, Medical doctor, +4550569536, gustav.riemer.jakobsen@regionh.dk
Lise Aunsholt, MD, ph.d., professor, +4561991137, lise.aunsholt@regionh.dk
About this study
Official title: PrePhage - Faecal Bacteriophage Transfer for Enhanced Gastrointestinal Tract Maturation in Preterm Infants - Clinical Trial
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).
Read more
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
- 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.
Read the 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
- Necrotizing Enterocolitis, Microbial Substitution
- Being tested
- Fecal Filtrate Transfer, Placebo
- Medical subject headings
- Enterocolitis, Necrotizing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal Filtrate TransferOther
Treatment with donated fecal samples filtered to contain practically no bacteria and mainly viruses, including bacteriophages
PlaceboOther
Saline solution
| Study group | Role | What they receive |
|---|---|---|
| FFT treatment | Experimental | Treatment with fecal filtrate transfer in saline solution administered by nasogastric tube Receives: Other: Fecal Filtrate Transfer |
| Placebo Treatment | Placebo comparator | Treatment with saline solution administered by nasogastric tube Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
No serious adverse events
No increased incidence of sepsis, NEC and death in the treatment group
Measured: 14 days
Secondary outcomes (12)
Feeding tolerance
Using a standardized clinical scoring system, nurses at our NICU will evaluate any negative reactions to enteral feeding. It includes evaluation of aspirate, feces, amount of enteral nutrition administered, objective evaluation of the abdomen, and signs of obstipation
Measured: 1 month
Microbiota Composition
Total genomic DNA will be subjected to deep metagenome sequencing and related to the study outcomes. When extracting faecal DNA as well as viral DNA/RNA, physical fractionation or selective lysis will be employed to ensure host DNA is kept to a minimum. Remaining host DNA material will be removed during bioinformatics filtering and mapping of the shotgun metagenomics data.
Measured: 1 month
Time to full enteral feeding
Measured: 1 month
Blood pressure
Blood pressure in mmHg
Measured: 1 month
Temperature
Rectal temperature in degrees celsius
Measured: 1 month
Pulse
Pulse measured using samsung monitoring equipment according to standard at our NICU
Measured: 1 month
Length
Length in cm
Measured: 1 month
Weight
Weight in kilograms
Measured: 1 month
Stool characteristics - Amount
Score from 1-4 using Amsterdam stool scale
Measured: 1 month
Stool characteristics - Consistency
Score from 1-6 using diapered infant stool scale
Measured: 1 month
Stool characteristics - Color
Score from 1-6 using Amsterdam Stool Scale
Measured: 1 month
Days of hospitalization
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2022
- Study start7 Nov 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Necrotizing EnterocolitisStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In a block randomized trial with 14 days of follow up between each step, a total of 10 infants will be treated with fecal filtrate transfer and 10 infants will be treated with placebo. The structure will be: 2+2, 2+2, 2+2, 6+6
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Lise Aunsholt, Neonatologist, Clinical Professor
- Responsible party
- Principal investigator, Gustav Riemer Jakobsen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Lise Aunsholt, md, phd, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05272579
- Sponsor's protocol ID
- Rigshospitalet - PrePhage
- Status last verified
- Nov 2024
- First submitted
- 15 Feb 2022
- Last updated
- 15 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: An anonomized version of the data will be published along with the main report from the intervention study
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.
PubMed 41051016
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PrePhage - Faecal Bacteriophage Transfer for Enhanced Gastrointestinal Tract Maturation in Preterm Infants - Clinical Trial
- ClinicalTrials.gov ID
- NCT05272579
- Acronym / sponsor ID
- Rigshospitalet - PrePhage
- Conditions
- Necrotizing Enterocolitis, Microbial Substitution
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- Lise Aunsholt, Neonatologist, Clinical Professor
- Study start
- 7 Nov 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 9 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- In a block randomized trial with 14 days of follow up between each step, a total of 10 infants will be treated with fecal filtrate transfer and 10 infants will be treated with placebo. The structure will be: 2+2, 2+2, 2+2, 6+6
| Arm | Type | Receives |
|---|---|---|
| FFT treatment | Experimental | Other: Fecal Filtrate TransferTreatment with fecal filtrate transfer in saline solution administered by nasogastric tube |
| Placebo Treatment | Placebo comparator | Other: PlaceboTreatment with saline solution administered by nasogastric tube |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
- Women aged 18-45
Key exclusion criteria (4 listed)
- 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
- ● 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fecal Filtrate TransferTreatment with donated fecal samples filtered to contain practically no bacteria and mainly viruses, including bacteriophages | Other | FFT treatment |
| PlaceboSaline solution | Other | Placebo Treatment |
Primary outcome
No serious adverse events
Time frame: 14 days
No increased incidence of sepsis, NEC and death in the treatment group
12 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2024.
- Derived from this study: PubMed 41051016Kappel 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.
- Individual participant dataSharing planned: Yes. An anonomized version of the data will be published along with the main report from the intervention study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lise Aunsholt, md, phd principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Fecal Filtrate Transfer in people with Necrotizing Enterocolitis and Microbial Substitution, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gustav R Jakobsen, md (+4550569536, gustav.riemer.jakobsen@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
No serious adverse events (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05272579, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2024.