Mixed Flora; InfectionPINGUNCT02197468
Preterm Infant Gut (PINGU) - a Norwegian Multi Centre Study
An observational study of Mixed Flora; Infection, run by University Hospital of North Norway at 7 sites in Norway.
Trial summary
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality among infants in the neonatal intensive care unit (NICU). It has been postulated that abnormal colonization of the preterm gut, or an unfavorable balance between gut bacteria may contribute to the development of NEC. Read more about this study
- Who is it for?
- Ages 1 hour to 12 months
- Conditions the study is for
- Mixed Flora; Infection
- How many people
- 60 participants
- Where
- 7 sitesNorway
- Study dates
- Mar 2015to Nov 2015
- How long will I take part?
- 1 Year
- Phase
- Observational
- Are there results?
- None posted in the registry
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 1 hour to 12 months
- All sexes
- No healthy volunteers
- Child
Study population: Preterm infants hospitalized in 6 Norwegian NICUs; divided in one group extremely preterm infants receiving probiotics and one group moderate preterm infants not receiving antibiotics. A group of helathy infants from the post-natal ward will also be included
Who may be able to join
- Preterm infants with gestational age 24-27 weeks/birth weight < 1000 g, treated with probiotics (target number 26)
- Preterm infants with gestational age 29-31 weeks/birth weight 1000-1500 g, not treated with probiotics (target number 26)
- Term infants (target number 10)
Who cannot join
- Extremely preterm infants with gestational age below 24 weeks
- Preterm infants (24-31 weeks) with life threatening complications during 1 week of age
- Infants with congenital malformations
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Norway7 sites
Haukeland Universtiy Hospital
Bergen, 5021
Oslo University Hospital, Rikshospitalet
Oslo, 0424
Oslo University Hospital, Ullevaal
Oslo, 0424
Ahus University Hospital
Oslo
Stavanger University Hospital
Stavanger, 4011
University Hospital of North Norway
Tromsø, 9038
St Olavs Hospital, Trondheim University Hospital
Trondheim, 7030
About this study
Official title: Gut Microbiome Study in Preterm Infants - a Norwegian Multi Centre Study
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality among infants in the neonatal intensive care unit (NICU). It has been postulated that abnormal colonization of the preterm gut, or an unfavorable balance between gut bacteria may contribute to the development of NEC.
Recent clinical randomized studies and meta-analysis have shown that proactive colonization of probiotic bacteria reduce the frequency of NEC. Based on this evidence, in April 2014 all Norwegian NICUs started routinely administration of probiotics to all extremely premature neonates susceptible to NEC (gestational age <28 weeks/birth weight <1000g).
Read more
The current project is investigating the gut microbiome in patients receiving probiotics and compare the the gut microbiome with moderate premature infants not receiving probiotics. In addition, we are including a control of healthy full-term infants.
Samples containing feces from participants will be analyzed by state of the art whole-genome sequencing techniques. Bacterial diversity will be analysed with bioinformatic tools.
Study hypotheses:
- Probiotics given to extremely preterm infants will change the biodiversity of the gut microflora.
- Antibiotics given to these patients may influence the gut microflora also in infants receiving probiotics. In particular use of vancomycin may change the gut flora.
- After cessation of probiotic prophylaxis the gut flora of infants receiving probiotics will gradually resemble the gut flora of infants not receiving probiotics.
- A cross-contamination of probiotic bacteria between patients treated with probiotics and patients not treated with antibiotics may occur.
Read the detailed description
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality among infants in the neonatal intensive care unit (NICU). Prematurity is the most important risk factor for NEC. The pathogenesis of NEC remains unclear, and prevention and treatment strategies are limited. It has been postulated that abnormal colonization of the preterm gut, or an unfavorable balance between gut bacteria, is significant in the pathogenesis of NEC.
Recent clinical randomized studies and meta-analysis have shown that proactive colonization of probiotic bacteria reduce the frequency of NEC. Based on this evidence, in April 2014 all Norwegian NICUs started routinely administration of probiotics to all extremely premature neonates susceptible to NEC (gestational age (GA) <28 weeks/birth birth weight (BW) <1000 g).
The current project is investigating the gut microbiome in patients receiving probiotics and compare the the gut microbiome with moderate premature infants not receiving probiotics. In addition, we are including a control of healthy full-term infants.
Samples containing feces from participants will be analyzed by state of the art whole-genome sequencing techniques. Bacterial diversity and taxonomy will be analysed using bioinformatic tools
Inclusion criteria:
- Preterm infants 24-27 weeks gestation/ birth weight < 1000 g receiving probiotics
- Preterm infants 28-31 weeks gestation/BW 1000-1500 g not receiving probiotics
- Healthy term infants
Exclusion criteria
- Preterm infants < 24 weeks gestation
- Preterm infants < 32 weeks with severe lethal complication/poor prognosis around 1 week of age
- Infants with severe congenital malformations
Fecal samples will be obtained:
- 1 week of age
- 4 weeks of age
- 4 months corrected age
- 12 months corrected age
Study hypotheses:
- Probiotics given to extremely preterm infants will change the biodiversity of the gut microflora.
- Antibiotics given to these patients may influence the gut microflora also in infants receiving probiotics. In particular use of vancomycin may change the gut flora.
- After cessation of probiotic prophylaxis the gut flora of infants receiving probiotics will gradually resemble the gut flora of infants not receiving probiotics.
- A cross-contamination of probiotic bacteria between patients treated with probiotics and patients not treated with antibiotics may occur.
This is an explorative study. No formal sample size assessment is possible. Sequencing costs will be substantial. We will limit the number of participants to 26 x 2 preterm infants and 10 control healthy infants.
Six Norwegian Neonatal Intensive care units wil participate in the study.
- Conditions
- Mixed Flora; Infection
- Keywords
- Gut microbiome, Necrotizing enterocolitis, Antibiotics
- Medical subject headings
- Infections, Enterocolitis, Necrotizing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Probiotics | Preterm infants given probiotics: GA 24-27 weeks/Birth weight < 1000 g Preterm infants not given probiotics: GA 28-31 weeks/Birth weight 1000-1500 g Full-term infants not given probiotics (control) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess gut microbiome composition (meta genome sequencing) of preterm infants receiving probiotics versus preterm infants not receiving probiotics
Stools samples from preterm infants and term infants (control)
Measured: 4 time points: 7 days of age, 4 weeks of age, 4 months corrected age and 12 months corrected age
Secondary outcomes (1)
Impact of antibiotic exposure on gut microbiome
Stool samples from preterm and term infants
Measured: 4 time points: 7 days of age, 4 weeks of age, 4 months corrected age and 12 months corrected age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2014 (estimated)
- Study startMar 2015
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Mixed Flora; InfectionStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- University Hospital of North Norway
- Sponsor type
- University, hospital or other
- Collaborators
- University of Tromso, Oslo University Hospital, Ullevaal University Hospital, St. Olavs Hospital, Haukeland University Hospital, Helse Stavanger HF
- Responsible party
- Sponsor
- Investigators
- Claus Klingenberg, MD.phD.Prof., Study chair, University Hospital of North NorwayEirin Esaiassen, MD, Principal investigator, University Hospital of North-Noway
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02197468
- Sponsor's protocol ID
- 2014/930 (REK)
- Acronym
- PINGU
- Status last verified
- Jun 2016
- First submitted
- 21 Jul 2014
- Last updated
- 11 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Berrington JE, Stewart CJ, Cummings SP, Embleton ND. The neonatal bowel microbiome in health and infection. Curr Opin Infect Dis. 2014 Jun;27(3):236-43. doi: 10.1097/QCO.0000000000000061.
PubMed 24751892Stewart CJ, Marrs EC, Magorrian S, Nelson A, Lanyon C, Perry JD, Embleton ND, Cummings SP, Berrington JE. The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection. Acta Paediatr. 2012 Nov;101(11):1121-7. doi: 10.1111/j.1651-2227.2012.02801.x. Epub 2012 Aug 31.
PubMed 22845166Esaiassen E, Hjerde E, Cavanagh JP, Pedersen T, Andresen JH, Rettedal SI, Stoen R, Nakstad B, Willassen NP, Klingenberg C. Effects of Probiotic Supplementation on the Gut Microbiota and Antibiotic Resistome Development in Preterm Infants. Front Pediatr. 2018 Nov 16;6:347. doi: 10.3389/fped.2018.00347. eCollection 2018.
PubMed 30505830
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gut Microbiome Study in Preterm Infants - a Norwegian Multi Centre Study
- ClinicalTrials.gov ID
- NCT02197468
- Acronym / sponsor ID
- PINGU / 2014/930 (REK)
- Conditions
- Mixed Flora; Infection
- Keywords
- Gut microbiome, Necrotizing enterocolitis, Antibiotics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University Hospital of North NorwayUniversity, hospital or other
- Collaborators
- University of Tromso, Oslo University Hospital, Ullevaal University Hospital, St. Olavs Hospital, Haukeland University Hospital, Helse Stavanger HF
- Study start
- Mar 2015
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 22 Jul 2014 (estimated)
- 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.
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality among infants in the neonatal intensive care unit (NICU). It has been postulated that abnormal colonization of the preterm gut, or an unfavorable balance between gut bacteria may contribute to the development of NEC.
Recent clinical randomized studies and meta-analysis have shown that proactive colonization of probiotic bacteria reduce the frequency of NEC. Based on this evidence, in April 2014 all Norwegian NICUs started routinely administration of probiotics to all extremely premature neonates susceptible to NEC (gestational age <28 weeks/birth weight <1000g).
The current project is investigating the gut microbiome in patients receiving probiotics and compare the the gut microbiome with moderate premature infants not receiving probiotics. In addition, we are including a control of healthy full-term infants.
Samples containing feces from participants will be analyzed by state of the art whole-genome sequencing techniques. Bacterial diversity will be analysed with bioinformatic tools.
Study hypotheses:
- Probiotics given to extremely preterm infants will change the biodiversity of the gut microflora.
- Antibiotics given to these patients may influence the gut microflora also in infants receiving probiotics. In particular use of vancomycin may change the gut flora.
- After cessation of probiotic prophylaxis the gut flora of infants receiving probiotics will gradually resemble the gut flora of infants not receiving probiotics.
- A cross-contamination of probiotic bacteria between patients treated with probiotics and patients not treated with antibiotics may occur.
Detailed description
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality among infants in the neonatal intensive care unit (NICU). Prematurity is the most important risk factor for NEC. The pathogenesis of NEC remains unclear, and prevention and treatment strategies are limited. It has been postulated that abnormal colonization of the preterm gut, or an unfavorable balance between gut bacteria, is significant in the pathogenesis of NEC.
Recent clinical randomized studies and meta-analysis have shown that proactive colonization of probiotic bacteria reduce the frequency of NEC. Based on this evidence, in April 2014 all Norwegian NICUs started routinely administration of probiotics to all extremely premature neonates susceptible to NEC (gestational age (GA) <28 weeks/birth birth weight (BW) <1000 g).
The current project is investigating the gut microbiome in patients receiving probiotics and compare the the gut microbiome with moderate premature infants not receiving probiotics. In addition, we are including a control of healthy full-term infants.
Samples containing feces from participants will be analyzed by state of the art whole-genome sequencing techniques. Bacterial diversity and taxonomy will be analysed using bioinformatic tools
Inclusion criteria:
- Preterm infants 24-27 weeks gestation/ birth weight < 1000 g receiving probiotics
- Preterm infants 28-31 weeks gestation/BW 1000-1500 g not receiving probiotics
- Healthy term infants
Exclusion criteria
- Preterm infants < 24 weeks gestation
- Preterm infants < 32 weeks with severe lethal complication/poor prognosis around 1 week of age
- Infants with severe congenital malformations
Fecal samples will be obtained:
- 1 week of age
- 4 weeks of age
- 4 months corrected age
- 12 months corrected age
Study hypotheses:
- Probiotics given to extremely preterm infants will change the biodiversity of the gut microflora.
- Antibiotics given to these patients may influence the gut microflora also in infants receiving probiotics. In particular use of vancomycin may change the gut flora.
- After cessation of probiotic prophylaxis the gut flora of infants receiving probiotics will gradually resemble the gut flora of infants not receiving probiotics.
- A cross-contamination of probiotic bacteria between patients treated with probiotics and patients not treated with antibiotics may occur.
This is an explorative study. No formal sample size assessment is possible. Sequencing costs will be substantial. We will limit the number of participants to 26 x 2 preterm infants and 10 control healthy infants.
Six Norwegian Neonatal Intensive care units wil participate in the study.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Year
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Probiotics | – | –Preterm infants given probiotics: GA 24-27 weeks/Birth weight < 1000 g Preterm infants not given probiotics: GA 28-31 weeks/Birth weight 1000-1500 g Full-term infants not given probiotics (control) |
Who may qualify
- Ages
- 1 hour to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Preterm infants hospitalized in 6 Norwegian NICUs; divided in one group extremely preterm infants receiving probiotics and one group moderate preterm infants not receiving antibiotics. A group of helathy infants from the post-natal ward will also be included
Key inclusion criteria (3 listed)
- Preterm infants with gestational age 24-27 weeks/birth weight < 1000 g, treated with probiotics (target number 26)
- Preterm infants with gestational age 29-31 weeks/birth weight 1000-1500 g, not treated with probiotics (target number 26)
- Term infants (target number 10)
Key exclusion criteria (3 listed)
- Extremely preterm infants with gestational age below 24 weeks
- Preterm infants (24-31 weeks) with life threatening complications during 1 week of age
- Infants with congenital malformations
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To assess gut microbiome composition (meta genome sequencing) of preterm infants receiving probiotics versus preterm infants not receiving probiotics
Time frame: 4 time points: 7 days of age, 4 weeks of age, 4 months corrected age and 12 months corrected age
Stools samples from preterm infants and term infants (control)
1 secondary outcome
Impact of antibiotic exposure on gut microbiome
Time frame: 4 time points: 7 days of age, 4 weeks of age, 4 months corrected age and 12 months corrected age
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2019.
- Background: PubMed 24751892Berrington JE, Stewart CJ, Cummings SP, Embleton ND. The neonatal bowel microbiome in health and infection. Curr Opin Infect Dis. 2014 Jun;27(3):236-43. doi: 10.1097/QCO.0000000000000061.
- Background: PubMed 22845166Stewart CJ, Marrs EC, Magorrian S, Nelson A, Lanyon C, Perry JD, Embleton ND, Cummings SP, Berrington JE. The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection. Acta Paediatr. 2012 Nov;101(11):1121-7. doi: 10.1111/j.1651-2227.2012.02801.x. Epub 2012 Aug 31.
- Derived from this study: PubMed 30505830Esaiassen E, Hjerde E, Cavanagh JP, Pedersen T, Andresen JH, Rettedal SI, Stoen R, Nakstad B, Willassen NP, Klingenberg C. Effects of Probiotic Supplementation on the Gut Microbiota and Antibiotic Resistome Development in Preterm Infants. Front Pediatr. 2018 Nov 16;6:347. doi: 10.3389/fped.2018.00347. eCollection 2018.
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. This study is not recruiting at the moment.
Claus Klingenberg, MD.phD.Prof. study chair
University Hospital of North Norway
Eirin Esaiassen, MD principal investigator
University Hospital of North-Noway
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mixed Flora; Infection, run by University Hospital of North Norway at 7 sites in Norway.
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 3 inclusion and 3 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: finished, as of the sponsor's last update on 11 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Norway. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess gut microbiome composition (meta genome sequencing) of preterm infants receiving probiotics versus preterm infants not receiving probiotics (time frame: 4 time points: 7 days of age, 4 weeks of age, 4 months corrected age and 12 months corrected age). 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 NCT02197468, which also lists 3 linked publications.
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 11 Mar 2019.