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Preterm Infant Gut (PINGU) - a Norwegian Multi Centre Study (PINGU)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02197468
Recruitment Status : Completed
First Posted : July 22, 2014
Last Update Posted : March 11, 2019
Sponsor:
Collaborators:
University of Tromso
Oslo University Hospital
Ullevaal University Hospital
St. Olavs Hospital
Haukeland University Hospital
Helse Stavanger HF
Information provided by (Responsible Party):
University Hospital of North Norway

Brief 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.

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.

Condition or disease
Mixed Flora; Infection

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.

Layout table for study information
Study Type : Observational [Patient Registry]
Actual Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 1 Year
Official Title: Gut Microbiome Study in Preterm Infants - a Norwegian Multi Centre Study
Study Start Date : March 2015
Actual Primary Completion Date : November 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine


Group/Cohort
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)




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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 ]
    Stool samples from preterm and term infants


Other Outcome Measures:
  1. Cross contamination of probiotic bacteria in a NICU [ Time Frame: 7 days of age and 4 weeks of age ]
    Detection of probiotic bacterial microbiome profiles in children not receiving probiotics


Biospecimen Retention:   Samples With DNA
Fecal samples for bacterial DNA analyses


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 12 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02197468


Locations
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Norway
Haukeland Universtiy Hospital
Bergen, Norway, 5021
Oslo University Hospital, Rikshospitalet
Oslo, Norway, 0424
Oslo University Hospital, Ullevaal
Oslo, Norway, 0424
Ahus University Hospital
Oslo, Norway
Stavanger University Hospital
Stavanger, Norway, 4011
University Hospital of North Norway
Tromsø, Norway, 9038
St Olavs Hospital, Trondheim University Hospital
Trondheim, Norway, 7030
Sponsors and Collaborators
University Hospital of North Norway
University of Tromso
Oslo University Hospital
Ullevaal University Hospital
St. Olavs Hospital
Haukeland University Hospital
Helse Stavanger HF
Investigators
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Study Chair: Claus Klingenberg, MD.phD.Prof. University Hospital of North Norway
Principal Investigator: Eirin Esaiassen, MD University Hospital of North-Noway

Additional Information:

Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Publication from this study

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University Hospital of North Norway
ClinicalTrials.gov Identifier: NCT02197468    
Other Study ID Numbers: 2014/930 (REK)
First Posted: July 22, 2014    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: June 2016
Keywords provided by University Hospital of North Norway:
Gut microbiome
Necrotizing enterocolitis
Antibiotics