Prophylactic Probiotics to Extremely Low Birth Weight Prematures (PROPEL)

This study is currently recruiting participants.
Verified July 2012 by Ostergotland County Council, Sweden
Sponsor:
Collaborators:
BioGaia AB
The Ekhaga Foundation, Sweden
Medical Research Council of Southeast Sweden
University Hospital, Linkoeping
Information provided by (Responsible Party):
Thomas Abrahamsson, Ostergotland County Council, Sweden
ClinicalTrials.gov Identifier:
NCT01603368
First received: May 18, 2012
Last updated: July 4, 2012
Last verified: July 2012
  Purpose

Mortality and incidence of severe complications is still high among extremely premature infants. Common causes of severe complications in this population are poor nutrition, necrotizing enterocolitis, and severe infections. Feeding intolerance is also a common problem resulting in prolonged need for intravenous lines and poor nutrition.

The aim of the study is to evaluate whether supplementation with the probiotic bacterium Lactobacillus reuteri DSM 17938 daily to premature infants with extremely low birth weight increases feeding tolerance to breast milk and thereby improves nutrition, increases growth and reduces serious complications and mortality in this population. Beyond this, possible mechanisms underlying these effects will be analyzed in stool, breast milk and blood samples.


Condition Intervention Phase
Feeding; Difficult, Newborn
Growth Failure
Necrotizing Enterocolitis
Sepsis
Dietary Supplement: Lactobacillus reuteri
Dietary Supplement: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Prophylactic Probiotics to Extremely Low Birth Weight Prematures

Resource links provided by NLM:


Further study details as provided by Ostergotland County Council, Sweden:

Primary Outcome Measures:
  • Time to establish full enteral feeds [ Time Frame: Birth to gestational week 36+0 ] [ Designated as safety issue: No ]
    The age of the infants in days when the infant receive 150 ml/kg/day via enteral feeding for the first time.


Secondary Outcome Measures:
  • Episodes with food intolerance [ Time Frame: Birth to gestational week 36 ] [ Designated as safety issue: No ]
    Episode with food intolerance. Retention volume> food volume given the last 2 hours (retention checked routinely every 4 hours) and/or clinical signs consistent with necrotizing enterocolitis (reduced general condition and inflated abdomen). The number of such events will also be indicated.

  • Stool frequency. [ Time Frame: Recorded over three days: gw35+0- 35+2 ] [ Designated as safety issue: No ]
  • Spitting/vomiting: the number recorded during the three days: v35 v35 +0- +2. [ Time Frame: gw 35+0-gw35+2. ] [ Designated as safety issue: No ]
    The number recorded during the three days

  • Crying [ Time Frame: gw35+0-35+2 ] [ Designated as safety issue: No ]
    defined as the cries for 3 hours or more during 3 days

  • Time until birth weight is regained. Specifies the number of full days the child has lived. [ Time Frame: Birth to gw 36+0 ] [ Designated as safety issue: No ]
    Specifies the number of full days the child has lived.

  • Weight, height and head circumference [ Time Frame: At 14 and 28 days of life and gw 36+0 ] [ Designated as safety issue: No ]
    In this analysis, the difference in standard deviation score (delta z-scores) for weight, height and head circumference at birth and 14 and 28 days and gestational week 36+0 will be calculated. At gestational week 36+0 also absolute values will be analyzed

  • Mortality [ Time Frame: Birth to gw 36+0 ] [ Designated as safety issue: Yes ]
  • Necrotizing enterocolitis [ Time Frame: Birth to gw 36+0 ] [ Designated as safety issue: No ]
    Bell´s criteria II-III

  • Sepsis [ Time Frame: Birth to gw 36+0 ] [ Designated as safety issue: No ]
    Divided into blood culture positive or clinical sepsis

  • Bronchopulmonary dysplasia [ Time Frame: Gw 36+0 ] [ Designated as safety issue: No ]
    Need of oxygen or CPAP/ventilator at gw 36+0


Estimated Enrollment: 134
Study Start Date: June 2012
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lactobacillus reuteri
Lactobacillus reuteri DSM 17938, 125 million bacteria/day
Dietary Supplement: Lactobacillus reuteri
Oil drops with Lactobacillus reuteri DSM 17938, 125 million bacteria=0.2 ml per day
Placebo Comparator: Placebo
The same oil drops as the active study product but without Lactobacillus reuteri
Dietary Supplement: Placebo
Oil drops without Lactobacillus reuteri

Detailed Description:

RATIONALE Mortality and incidence of severe complications is still high among extremely premature infants. Common causes of severe complications in this population are poor nutrition, necrotizing enterocolitis (NEC), and severe infections. Feeding intolerance is also a common problem resulting in prolonged need for intravenous lines and poor nutrition. There is scientific evidence that dietary supplements with probiotics may have an effect on these manifestations.

Lactobacillus reuteri is a well studied probiotic bacterium that has been tested in several clinical studies in premature infants and older children, and the results of these studies and animal studies suggest that this bacterium may also have an effect on growth and mortality in extremely premature infants. Lactobacillus reuteri reduces colonization with pathogenic microbes, stimulates gastric and intestinal motility and shortens hospital stay in moderately premature infants. In animal models, L. reuteri also induces anti-inflammatory immune responses, reduces the symptoms of inflammatory bowel disease and the incidence of NEC. Administration of L. reuteri also improves the intestinal barrier both in human studies in children and in animal studies. Dietary supplements of L. reuteri to extremely premature infants may therefore improve feeding tolerance and nutrition and reduce the incidence of severe complications in this population.

HYPOTHESIS Premature infants with extremely low birth weight receiving daily supplements of Lactobacillus reuteri DSM 17938 will reach full enteral feeding faster compared with children receiving placebo.

STUDY DESIGN This study will be conducted as a prospective multi-center double blind placebo-controlled study in neonatal intensive care units in Sweden. In total 134 neonates with extremely low birth weight (<1000g) and gestational age <28+0 weeks will be randomized to receive either dietary supplements of Lactobacillus reuteri or placebo. Study product will be identical to the active and placebo group besides the addition of Lactobacillus reuteri (1.25 x 100 million bacteria=0.2 ml oil drops per day) in the active group. The supplementation will commence within 1-3 days after birth and will be given daily until gestational week 36+0. The infants will be followed until gestational week 36+0 and data on feeding tolerance, nutrition, growth, infections, NEC, bronchopulmonary dysplasia, death, and potential confounders will be entered in an individual study protocol. Stool, breast milk, and blood samples will be collected for analyses of possible underlying mechanisms.

  Eligibility

Ages Eligible for Study:   up to 3 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Birth weight < 1000 g
  • Gestational age: v23+0-V27 +6.
  • Age < 72 hours at inclusion.
  • Signed informed consent by parents.

Exclusion Criteria:

  • Fatal or complex congenital malformation at inclusion time.
  • Chromosomal defect at inclusion time.
  • No realistic hope of survival at inclusion time.
  • Gastrointestinal malformation at inclusion time.
  • Participation in another study which aims to influence nutrition, growth, feeding tolerance or necrotizing enterocolitis.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01603368

Contacts
Contact: Thomas Abrahamsson, MD, PhD 0046-709-566815 thoab@telia.com
Contact: Erik Wejryd, MD 0046-10-1030000 erik.wejryd@lio.se

Locations
Sweden
Linköping University Hospital Recruiting
Linköping, Sweden, SE-581 85
Contact: Erik Wejryd, MD    0046-10-1030000    erik.wejryd@lio.se   
Principal Investigator: Thomas Abrahamsson, MD, PhD         
Sub-Investigator: Erik Wejryd, MD         
Karolinska Recruiting
Stockholm, Sweden, SE-171 76
Contact: Veronica Petermann, MD    0046-8-517 000 00    veronica.petermann@karolinska.se   
Sub-Investigator: Veronica Petermann, MD         
Sponsors and Collaborators
Ostergotland County Council, Sweden
BioGaia AB
The Ekhaga Foundation, Sweden
Medical Research Council of Southeast Sweden
University Hospital, Linkoeping
Investigators
Principal Investigator: Thomas Abrahamsson, MD, PhD Linköping University Hospital; County Council of Östergötland
  More Information

No publications provided

Responsible Party: Thomas Abrahamsson, MD, PhD, Neonatologist, Ostergotland County Council, Sweden
ClinicalTrials.gov Identifier: NCT01603368     History of Changes
Other Study ID Numbers: Dnr 2012/28-31
Study First Received: May 18, 2012
Last Updated: July 4, 2012
Health Authority: Sweden: The National Board of Health and Welfare

Keywords provided by Ostergotland County Council, Sweden:
Probiotics
Lactobacillus reuteri
Prematures
Enteral feeding
Motility
Necrotizing enterocolitis
Sepsis
Weight

Additional relevant MeSH terms:
Birth Weight
Enterocolitis
Failure to Thrive
Sepsis
Enterocolitis, Necrotizing
Body Weight
Signs and Symptoms
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Growth Disorders
Pathologic Processes
Infection
Systemic Inflammatory Response Syndrome
Inflammation

ClinicalTrials.gov processed this record on April 17, 2014