An Early Phase 1 interventional study of Fecal Filtrate Transfer and Placebo in Necrotizing Enterocolitis and Microbial Substitution, sponsored by Rigshospitalet, Denmark. Recruiting at 1 site in Denmark. Per ClinicalTrials.gov, last updated 2024-11-15.
Sponsored by Rigshospitalet, Denmark · Early Phase 1, Interventional, and Treatment
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:
If this pilot trial shows promising results, it will be followed be a larger clinical trial.
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.
228 studies on the registry are indexed under Enterocolitis, Necrotizing; 44 are open to participants now.
This study's planned enrollment of 20 is below the median of 103 across 127 interventional studies indexed under Enterocolitis, Necrotizing.
Browse Enterocolitis, Necrotizing studies →Rigshospitalet, Denmark is the lead sponsor of 1,007 studies on the registry; 175 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Inclusion criteria for participant preterm infants
Exclusion criteria for participant preterm infants
Inclusion criteria for mothers of participants
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)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Treatment with fecal filtrate transfer in saline solution administered by nasogastric tube
Other: Fecal Filtrate Transfer
Treatment with saline solution administered by nasogastric tube
Other: Placebo
Treatment with donated fecal samples filtered to contain practically no bacteria and mainly viruses, including bacteriophages
Saline solution
No serious adverse events
No increased incidence of sepsis, NEC and death in the treatment group
Time frame: 14 days
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
Time frame: 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.
Time frame: 1 month
Time to full enteral feeding
Time frame: 1 month
Blood pressure
Blood pressure in mmHg
Time frame: 1 month
Temperature
Rectal temperature in degrees celsius
Time frame: 1 month
Pulse
Pulse measured using samsung monitoring equipment according to standard at our NICU
Time frame: 1 month
Length
Length in cm
Time frame: 1 month
Weight
Weight in kilograms
Time frame: 1 month
Stool characteristics - Amount
Score from 1-4 using Amsterdam stool scale
Time frame: 1 month
Stool characteristics - Consistency
Score from 1-6 using diapered infant stool scale
Time frame: 1 month
Stool characteristics - Color
Score from 1-6 using Amsterdam Stool Scale
Time frame: 1 month
Days of hospitalization
Time frame: 1 month
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — An anonomized version of the data will be published along with the main report from the intervention study
Supporting information: Study protocol, Informed consent form, Clinical study report, Analytic code
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