Probiotics in the Management of Necrotizing Enterocolitis in HIV-exposed Premature Infants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Evette van Niekerk, University of Stellenbosch
ClinicalTrials.gov Identifier:
NCT01868737
First received: May 30, 2013
Last updated: July 19, 2013
Last verified: June 2013
  Purpose

A randomized, double blind, placebo controlled clinical trial was conducted in the neonatal high care unit of Tygerberg Children's Hospital (TBCH) Cape Town, South Africa for the period July 2011 to August 2012. The primary objective of the study was to assess the effect of probiotics on the incidence of NEC in high risk infants born to HIV-positive and HIV-negative women.

Throughout the study period, the standard of care protocol consisted of one dose (5 drops) probiotic/placebo daily for 4 weeks (28 days). This provided the study group with L. rhamnosus GG (0.35 x 109 colony-forming units [CFU]) and B. infantis (0.35 x 109 CFU) daily. The control group received placebo consisting of medium chain triglyceride (MCT) oil. Supplementation of the probiotic/placebo was initiated when enteral feeds started. Probiotic/ placebo supplementation was delayed/ halted in the event of: the infants being nill per os (NPO); when a query Necrotizing Enterocolitis (NEC) was suspected the infant continued with treatment until a confirmed a positive diagnosis of NEC I was made through abdominal X-ray; if the infant remained a query NEC and was NPO the infant did not receive probiotics/ placebo until the enteral feeds were commenced again. Supplementation was discontinued when HIV-exposed infants had a positive polymerase chain reaction (PCR) result on day 14 of life.

All study participants received human breast milk. Both the probiotics and placebo were mixed with the mothers own breast milk or donor breast milk before administration via the orogastric tube or orally. The probiotic/ placebo was added to the breast milk by the researcher and two research assistants who were blinded and not involved in the routine care of the infants. Participants exited the study on day 28 after birth or upon discharge from the hospital.


Condition Intervention Phase
Necrotizing Enterocolitis
Dietary Supplement: Probiotic
Dietary Supplement: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Use of Probiotics in the Management of Necrotizing Enterocolitis in HIV-exposed Premature and Very-low Birth Weight Infants

Resource links provided by NLM:


Further study details as provided by University of Stellenbosch:

Primary Outcome Measures:
  • Probiotics administration in reducing the incidence and severity of NEC (as per Bell's criteria19) in premature very-low birth weight infants that are exposed to HIV. [ Time Frame: Each infant received supplementation for 28 days ] [ Designated as safety issue: No ]
    Lactobacillus rhamnosus GG and Bifidobacterium infantis have been used as probiotics to reduce the incidence of NEC. The Product that was used is Pro-B2, it contains L. rhamnosus GG and B. infantis. The product was supplied by C Pharm. The study group received L. rhamnosus GG and B. infantis for 4 weeks (28 days). The control group received a placebo oil preparation, administered as drops of the oil vehicle used in manufacturing the Lactobacillus rhamnosus GG and Bifidobacterium infantis suspensions. A daily dose of 5 drops of the probiotic/ placebo was administered to the infants. The probiotics/ placebo was administered by the research assistant or investigator who only followed the assigned randomization of groups. The standard feeding protocol of the ward applied during the study. The breast milk of HIV positive mothers were pasteurised according to ward protocol.


Secondary Outcome Measures:
  • The prebiotic quality known as oligosaccharides of pasteurised own mothers breast milk of HIV positive and HIV negative mothers [ Time Frame: 3 milk samples in 38 days ] [ Designated as safety issue: No ]

    Breast milk samples of HIV positive and HIV negative breast milk was tested. All breast milk samples were raw untreated specimens therefore milk samples did not undergo any pasteurization procedures Breast milk was collected in sterilised containers with lids Each sample contained a volume of 5-10ml of breast milk for the analysis

    Sample 1 The first milk sample was collected on day four of lactation Sample 2 The second milk sample was collected on the tenth day of lactation Sample 3 The third sample was collected on the final day of the study

    Day 28 after birth and the end of the neonatal period If a mother was unavailable during the breast milk sample collection the breast milk samples were collected during the first available time All milk samples were collected by the investigator or research assistant who was standardized for all protocol procedures



Other Outcome Measures:
  • The association between the prebiotic quality of breast milk and the incidence of NEC in premature very-low birth weight infants [ Time Frame: 3 milk samples in 28 days ] [ Designated as safety issue: No ]
    Lactobacillus rhamnosus GG and Bifidobacterium infantis have been used as probiotics to reduce the incidence of NEC. The Product that was used is Pro-B2, it contains L. rhamnosus GG and B. infantis. The product was supplied by C Pharm. The study group received L. rhamnosus GG and B. infantis for 4 weeks (28 days). The control group received a placebo oil preparation, administered as drops of the oil vehicle used in manufacturing the Lactobacillus rhamnosus GG and Bifidobacterium infantis suspensions. A daily dose of 5 drops of the probiotic/ placebo was administered to the infants. The probiotics/ placebo was administered by the research assistant or investigator who only followed the assigned randomization of groups. The standard feeding protocol of the ward applied during the study. The breast milk of HIV positive mothers were pasteurised according to ward protocol.

  • Weight gain for both probiotic exposed and unexposed premature very-low birth weight infants [ Time Frame: Weight daily. Head circumfernce and length weekly. total follow-up was 28 days ] [ Designated as safety issue: No ]

    All study infants were weighed daily by the nursing staff. Weights were taken for study infants that were incubated and those that were not. Daily weights were recorded from each participant's medical file by the investigator or research assistant. Any drastic weight chances were queried and the measurement was repeated under supervision of the investigator or research-assistants.

    Infants were measured on day one of the study thereafter the length and head circumference was measured weekly. Upon exiting the study (day 28), the length and head circumference was measured again. Therefore five measurements on days 1, 7, 14, 21, 28 were taken.



Enrollment: 184
Study Start Date: July 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HIV exposed infants
Probiotic: L. rhamnosus GG (0.35 x 109 colony-forming units [CFU]) and B. infantis (0.35 x 109 CFU) daily
Dietary Supplement: Probiotic
Lactobacillus rhamnosus GG and Bifidobacterium infantis'
Other Names:
  • Brand name: Pro-B2
  • Lactobacillus rhamnosus GG and Bifidobacterium infantis'
Placebo Comparator: HIV- exposed infants
MCT oil
Dietary Supplement: Placebo
MCT oil
Placebo Comparator: HIV-unexposed infants
MCT oil
Dietary Supplement: Placebo
MCT oil
Experimental: HIV-unexposed
Probiotic: L. rhamnosus GG (0.35 x 109 colony-forming units [CFU]) and B. infantis (0.35 x 109 CFU) daily
Dietary Supplement: Probiotic
Lactobacillus rhamnosus GG and Bifidobacterium infantis'
Other Names:
  • Brand name: Pro-B2
  • Lactobacillus rhamnosus GG and Bifidobacterium infantis'

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   25 Weeks to 34 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  • Consecutive HIV positive or negative mothers, who gave birth to a premature, very-low birth weight infant at Tygerberg Childrens Hospital (TBCH) and consented to participate in the study.
  • Only mothers who decided to breastfeed after counseling, regardless of their HIV status were included
  • All HIV positive mothers are counseled routinely at TBCH about the risks and benefits of breastfeeding and bottle-feeding relating to the prevention of mother to child transmission scheme.
  • HIV positive mothers that were on the PMTCT treatment regiment and if antiretroviral medication was prescribed. Mothers receiving Nevirapine and Zidovudine as well as those receiving highly active antiretroviral medication were included in the study.

Premature/ low birth weight infants

  • Admission or transfer's to wards G1, G2, J3 and G8 at TBCH
  • Patients who were transferred to the kangaroo mother care unit in TBCH
  • Birth weight <1 250g
  • Premature infant with a birth age of <34 weeks gestation
  • Male and female subjects
  • Patients that received own mother's breast milk
  • Patients that received donor breast milk due to the following circumstances:
  • If donor breast milk was given as a supplemental feed due to insufficient breast milk supply from the mother
  • When the mother was unavailable e.g. home visits over weekends, continuation of work
  • If the mother was ill and unable to breastfeed the infant e.g. ICU admission
  • Premature very-low birth weight infants that were HIV exposed or HIV unexposed
  • HIV exposed premature very-low birth weight infants that received ARV medication

Exclusion Criteria:

  • Mothers that received medications that is contra-indicated for breastfeeding
  • These medications include the following drug classes: anticoagulants, cytotoxics and psychoactive drugs e.g. antidepressants , antipsychotics chlorpromazine and individual drugs detectable in breast milk that pose theoretical risk.
  • Mothers with active Mycobacterium tuberculosis who were still potentially infectious and who should not have been in direct contact with the infant were be excluded from this study
  • HIV positive mothers that presented clinically sick with a CD4 cell count <200cells/µl

Premature/ low birth weight infants

  • Birth weight < 500g
  • Premature infant with a birth age of <25 weeks gestation
  • Prenatal/ postnatal diagnosis of gastroschisis, large omphalocele or congenital diaphragmatic hernia
  • Infants with congenital intestinal obstruction or perforation
  • Infants with major congenital malformations and/or developmental disabilities pertaining to the gastrointestinal tract
  • Infants with perinatal asphyxia
  • Infants with a positive diagnosis of a complex heart disease
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01868737

Locations
South Africa
Tygerberg Hospital
Tygerberg, Cape town, Western Cape, South Africa, 7500
Sponsors and Collaborators
University of Stellenbosch
Investigators
Principal Investigator: Evette van Niekerk, M Dietetics University of Stellenbosch
  More Information

No publications provided by University of Stellenbosch

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Evette van Niekerk, Principal investigator, University of Stellenbosch
ClinicalTrials.gov Identifier: NCT01868737     History of Changes
Other Study ID Numbers: M10/09/035
Study First Received: May 30, 2013
Last Updated: July 19, 2013
Health Authority: South Africa: Department of Health

Keywords provided by University of Stellenbosch:
Human Immunodeficiency Virus
Necrotizing Enterocolitis
Premature infant
Probiotic
Very Low Birth Weight

Additional relevant MeSH terms:
Enterocolitis
Enterocolitis, Necrotizing
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on September 18, 2014