None listed
Conditions
Brief summary
Background Probiotics significantly reduce the risk of death, and serious complications (e.g. necrotising enterocolitis- an inflammatory bowel condition with high risk of death and disability, and hospital acquired infections), and improve nutrition in premature babies. However, despite the overwhelming evidence, acceptance of probiotics as a standard of care for premature babies has been slow considering the associated risks including infection due to probiotic bacteria, development of antibiotic resistance, and altered immune responses. Emerging evidence indicates that heat inactivated/killed probiotic bacteria (‘Paraprobiotics’) may provide a safe and effective alternative to probiotics (live bacteria) by overcoming their risks while retaining their benefits. Objectives The objectives of our novel pilot study comparing paraprobiotic vs. probiotic focus on finding a safe and effective alternative to probiotics. Results of our study have the potential to guide research on paraprobiotics for reducing death and disability in a wide range of population across the world (e.g. mature infants with surgical conditions of the intestine, children with inflammatory bowel disease, and immunocompromised adults) where probiotics are not used or evaluated due to their risks. Trial plan This pilot double blinded randomized controlled trial will be conducted over a period of 12-18 months (May 2018- November 2019) at King Edward Memorial Hospital. Very preterm infants < 32 weeks with specified inclusion and exclusion criteria will be recruited. Approval will be obtained from the KEMHW ethics committee. Therapeutic Goods Administration (TGA) and Clinical Trial Notification (CTN) approval will be obtained for importing the live and heat inactivated/killed probiotics from Japan. The trial protocol will be registered with the Australia New Zealand Clinical Trial Registry. Specified primary and secondary outcomes (clinical and laboratory based) will be measured.
Interventions
Intervention: Heat inactivated parabiotic containing a mixture of 3 strains (B. breve M-16V, B. longum subsp. infantis M-63 and B. longum subsp. longum BB536 (1×109 of each strain per 1 g sachet: 3-strains group), Morinaga Milk Industries, Japan. The mixture is inactivated by exposing the culture tank to 90° C for 15min.
Dose administered:
Both live and para probiotic supplementation will be commenced orally after informed consent and when baby is ready to start on enteral feeds.
When enteral
Intervention: Heat inactivated parabiotic containing a mixture of 3 strains (B. breve M-16V, B. longum subsp. infantis M-63 and B. longum subsp. longum BB536 (1×109 of each strain per 1 g sachet: 3-strains group), Morinaga Milk Industries, Japan. The mixture is inactivated by exposing the culture tank to 90° C for 15min. Dose administered: Both live and para probiotic supplementation will be commenced orally after informed consent and when baby is ready to start on enteral feeds. When enteral feeds < 50ml/kg/day, 1 ml (1.5 billion CFU) administered once daily When enteral feeds > 50 ml/kg/day: 1 ml twice daily (3 billion CFU/ day) will be administered Duration of administration: From commencement of enteral feeds till 37 completed weeks of gestation Both the live and para probiotic lyophilized dried preparation will be reconstituted using sterile techniques with distilled water and mum's own breast milk (when available). To check adherence to the intervention: The principal investigator will be responsible for ensuring adherence to trial protocol and will report any violations to the local ethics committee (Women and Newborn Health Ethics Research Committee).
Sponsors
King Edward Memorial Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
1 Hours to 7 Days
Healthy volunteers
No
Inclusion criteria
Eligibility criteria: (1) Gestation <32 weeks at birth (2) ready to commence on feeds or on feeds for less than or equal to 12 hours (3) Informed parental consent
Exclusion criteria
Exclusion criteria: (1) Congenital malformations (2) Chromosomal aberrations (3) Not ready for feeds or on feeds for >12 hours
Outcome results
None listed