Clinical trial NCT01956916: Probiotics in Cystic Fibrosis
Official title: Effects of LGG Administration in Children With Cystic Fibrosis: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: Pulmonary exacerbation
Inflammation
Intestinal microbiota
Lead sponsor: Federico II University
Sponsor class: OTHER
First posted: 2013-10-08
Enrollment: 110
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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
2. Boys and girls between 2 and 16 years of age
3. 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
4. Pancreatic insufficiency
5. Basal Forced Expiratory Volume 1 second above 50% of predicted value

Exclusion Criteria:

1. Colonization of respiratory tract with Burkholderia cepacia spp.
2. Steroid therapy within one month before enrolment
3. Pregnancy and fertile women taking oral contraceptives
4. Parenteral or oral antibiotics therapy within 2 weeks before enrolment
5. Regular assumption of probiotics
6. Regular assumption of azythromycin

Primary outcomes:
measure: Change in the incidence of pulmonary exacerbations from baseline to 12 months of treatment
timeFrame: every six months up to 18 months
measure: Change of intestinal inflammation from baseline to 12 months of treatment
timeFrame: every six months up to 18 months
Secondary outcomes:
measure: Change in the incidence of hospital admission from baseline to 12 months of treatment
timeFrame: every six month up to 18 months
measure: change in pulmonary function from baseline to 12 months of treatment (measured by Forced Expiratory Volume 1 sec (FEV1))
timeFrame: every six months up to 18 months
Other outcomes:
measure: Change in the incidence of abdominal pain episodes from baseline to 12 months of treatment
timeFrame: every six months up to 18 months
measure: Change in systemic inflammation from baseline to 12 months of treatment
timeFrame: At baseline and after 12 months of treatment
measure: Change of intestinal microflora composition from baseline to 12 months of treatment
timeFrame: baseline and 12 months after treatment
Locations:
city: Florence
country: Italy
facility: - Department of Paediatric Medicine, CF Center, "A. Meyer" Children's Hospital
city: Messina
country: Italy
facility: Dipartimento di Pediatria - Università Di Messina
city: Milano
country: Italy
facility: Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena
city: Napoli
country: Italy
facility: Università degli studi di Napoli "Federico II"
city: Rome
country: Italy
facility: Ospedale "Bambino Gesù" - Roma
Study officials:
References:
citation: Bruzzese E, Raia V, Spagnuolo MI, Volpicelli M, De Marco G, Maiuri L, Guarino A. Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: a pilot study. Clin Nutr. 2007 Jun;26(3):322-8. doi: 10.1016/j.clnu.2007.01.004. Epub 2007 Mar 13.
citation: Bruzzese E, Raia V, Gaudiello G, Polito G, Buccigrossi V, Formicola V, Guarino A. Intestinal inflammation is a frequent feature of cystic fibrosis and is reduced by probiotic administration. Aliment Pharmacol Ther. 2004 Oct 1;20(7):813-9. doi: 10.1111/j.1365-2036.2004.02174.x.
citation: Raia V, Maiuri L, de Ritis G, de Vizia B, Vacca L, Conte R, Auricchio S, Londei M. Evidence of chronic inflammation in morphologically normal small intestine of cystic fibrosis patients. Pediatr Res. 2000 Mar;47(3):344-50. doi: 10.1203/00006450-200003000-00010.
citation: Lucidi V, Alghisi F, Raia V, Russo B, Valmarana L, Valmarana R, Coruzzo A, Beschi S, Dester S, Rinaldi D, Maglieri M, Guidotti ML, Ravaioli E, Pesola M, De Alessandri A, Padoan R, Grynzich L, Ratclif L, Repetto T, Ambroni M, Provenzano E, Tozzi AE, Colombo C. Growth assessment of paediatric patients with CF comparing different auxologic indicators: A multicentre Italian study. J Pediatr Gastroenterol Nutr. 2009 Sep;49(3):335-42. doi: 10.1097/MPG.0b013e31818f0a39.
citation: Miragoli F, Federici S, Ferrari S, Minuti A, Rebecchi A, Bruzzese E, Buccigrossi V, Guarino A, Callegari ML. Impact of cystic fibrosis disease on archaea and bacteria composition of gut microbiota. FEMS Microbiol Ecol. 2017 Feb;93(2):fiw230. doi: 10.1093/femsec/fiw230. Epub 2016 Nov 2.