Probiotics in Cystic Fibrosis

Study Overview
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Brief Summary
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Cystic fibrosis (CF) is a complex systemic disease that mainly involves the respiratory and gastrointestinal (GI) tracts. The polymicrobial community composition of respiratory and GI tracts is influenced by both genetic and environmental factors. Children with CF may harbor an abnormal intestinal microflora, because of altered cystic fibrosis transmembrane conductance regulator (CFTR) function and heavy drug load (antibiotics, pancreatic enzymes and acid suppressors). The investigators have previously demonstrated that intestinal inflammation is highly frequent in CF children, being a major feature of intestinal involvement. In addition, specific probiotics significantly improved airway and GI inflammation in a preliminary trial. The investigators aim to characterize intestinal and respiratory microflora in CF patients and to investigate the effects of daily Lactobacillus GG (LGG) supplementation on both GI and airway microflora and the eventual relationship between probiotic assumption and clinical and inflammation markers. The investigators aim is to eventually improve the quality of life of CF patients, who often suffer from intestinal and respiratory progressive disease, through a non invasive intervention consisting in the supplementation of probiotic bacteria.

Official Title
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Effects of LGG Administration in Children With Cystic Fibrosis: A Randomized Controlled Trial

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Dietary Supplement: Lactobacillus rhamnosus GG
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A confirmed diagnosis of CF documented by sweat chloride test over 60 mmol/L and confirmed by genotype analysis with the presence of F508del/F508del or F508del/other Boys and girls between 2 and 16 years of age Clinical stability at enrolment, defined as no clinical evidence of acute exacerbation, no modifications in the therapeutic regimen and no hospitalization in the last 2 weeks Pancreatic insufficiency Basal Forced Expiratory Volume 1 second above 50% of predicted value Exclusion Criteria: Colonization of respiratory tract with Burkholderia cepacia spp. Steroid therapy within one month before enrolment Pregnancy and fertile women taking oral contraceptives Parenteral or oral antibiotics therapy within 2 weeks before enrolment Regular assumption of probiotics Regular assumption of azythromycin

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotics<br>Capsules containing lyophilized 6x10^9 Colony Forming Units (CFU)/die of Lactobacillus rhamnosus GG (LGG) | Dietary Supplement: Lactobacillus rhamnosus GG<br>* Capsules containing lyophilized 6x10^9 Colony Forming Units (CFU)/die LGG, (60mg) maltodextrin (163 mg), gelatine capsule (75 mg), magnesium stearate (2 mg) 1 cps/die for 12 months<br>* Other names: LGG;|
| Placebo Comparator: Placebo<br>Capsules containing maltodextrin | Dietary Supplement: placebo<br>* Capsules containing maltodextrin (163 mg), gelatine capsule (75 mg), magnesium stearate (2 mg) 1 cps/die for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the incidence of pulmonary exacerbations from baseline to 12 months of treatment | The incidence of pulmonary exacerbation is assessed every six months. First evaluation from baseline to 6 months of observation. Second evaluation from randomization ( placebo/LGG) to 6 months of treatment and third evaluation after 12 months of treatment | every six months up to 18 months | 
| Change of intestinal inflammation from baseline to 12 months of treatment | Assessment of intestinal inflammation is performed four times. First time at enrollment, second time at the end of six months of observation. Third time after six months of treatment and fourth time after 12 months of treatment. | every six months up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the incidence of hospital admission from baseline to 12 months of treatment | The incidence of hospital admission is assessed every six months. First evaluation from baseline to 6 months of observation. Second evaluation from randomization ( placebo/LGG) to 6 months of treatment and third evaluation after 12 months of treatment | every six month up to 18 months | 
| change in pulmonary function from baseline to 12 months of treatment (measured by Forced Expiratory Volume 1 sec (FEV1)) | Assessment of pulmonary function is performed four times. First time at enrollment, second time at the end of six months of observation. Third time after six months of treatment and fourth time after 12 months of treatment. | every six months up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary exacerbation, Inflammation, Intestinal microbiota