None listed
Conditions
Brief summary
The PEARL-CF study is a multi-center, double-blind, randomized, placebo-controlled trial comparing three cohorts: (1) Children with cystic fibrosis (CF) taking a probiotic daily for 1 year, (2) Children with CF taking a placebo daily for 1 year, and (3) Healthy non-CF controls (HC) not on probiotics or placebo (age and gender matched). The hypothesis is that: (i) Probiotics restore the abnormal gut microbiota in children with CF, which in turn reduces intestinal inflammation. We also hypothesize that when: (ii) Probiotics are administered daily for 1 year, they will have clinical benefits for patients with CF. (iii) Probiotics are administered in early life (0-3 years), the effects, even when ceased, are sustained compared to when probiotics are given after the gut microbiota has become established (~3 years old).
Interventions
This is a double-blind, randomised, placebo-controlled study in children comparing three cohorts:
(1) Subjects with CF taking probiotics,
(2) Subjects with CF taking a placebo, and
(3) Healthy non-CF controls (not on probiotics/placebo) matched to CF subjects (age and gender).
All subjects with CF will be randomised to either receive probiotic or placebo administered once daily for 12 months. Healthy controls do not receive probiotics or placebo.
Randomisation among CF subjects will be strat
This is a double-blind, randomised, placebo-controlled study in children comparing three cohorts: (1) Subjects with CF taking probiotics, (2) Subjects with CF taking a placebo, and (3) Healthy non-CF controls (not on probiotics/placebo) matched to CF subjects (age and gender). All subjects with CF will be randomised to either receive probiotic or placebo administered once daily for 12 months. Healthy controls do not receive probiotics or placebo. Randomisation among CF subjects will be stratified according to the 2 age groups (0-3 and >3-6 years old) and performed as block randomization with a 1:1 allocation by an independent statistician. This age stratification is performed to evaluate the effects of probiotics when given at ages prior and after the age when the adult gut microbiota has normally established itself (~3 years old). 2g and 3g of probiotic or placebo powder will be administered daily to children 0-3 years and >3-6 years respectively. The powder allows for easy administration in infants and children, as it can be mixed into milk, juice, food (but avoiding hot drinks or food) or consumed directly off the spoon. Parents will be given a 2 months supply and instructed to store the probiotic appropriately at room temperature. A further 2 month supply will be provided at each stool sampling time point during the 12 months. Selection of probiotic micro-organisms A probiotic combination of Lactobacillus and Bifidobacterium spp will be used in this study. Strains CFUs Bifidobacterium lactis BI-04 3 Billion Lactobacillus rhamnosus GG 2 Billion Lactobacillus paracasei Lpc-37 1 Billion Lactobacillus plantarum Lp-115 1 Billion Lactobacillus rhamnosus HN001 500 Million Lactobacillus rhamnosus Lr32 500 Million Bifidobacterium animalis HN019 500 Million Lactobacillus salivarius subsp. salivarius Ls-33 400 Million Streptococcus thermophiles St21 400 Million Bifidobacterium breve Bb-03 200 Million Lactobacillus gasseri Lg 36 200 Million Bifidobacterium longum BI-05 180 Million Bifidobacterium infantis Bi-26 100 Million Lactobacillus reuteri 1e1 100 Million Lactobacillus bulgaricus Lb-64 100 Million Excipient: Litesse Ultra (Polydextrose) 950 mg Total (15 Strains) CFU per 1g: 10.2 Billion For the control arm, at each stool collection time-point, the study investigator will enquire if participants are self-administering probiotics.
Sponsors
Sydney Children's Hospitals Network
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
No minimum to 6 Years
Healthy volunteers
Yes
Inclusion criteria
(1) All subjects with CF must fulfil the diagnostic criteria for CF (sweat chloride greater or equal to 60 mmol/L and/or 2 CF-causing mutations). (2) Healthy controls include healthy full term infants (38-40 weeks gestation; >2.5kg birth weight), and who do not have any major non-CF disease (e.g. spina bifida) or gut disease (e.g. inflammatory bowel disease).
Exclusion criteria
1) Patients with CF who have had previous intestinal surgery (e.g. meconium ileus) and/or have intestinal resection resulting in short gut syndrome. (2) Any CF subject already on probiotics but who are not willing to stop supplementation for 3 months prior to randomization. (3) Healthy controls on probiotics who are not willing to stop.
Outcome results
None listed