Probiotics on Intestinal Inflammation in Cystic Fibrosis

Effect of Probiotics on Intestinal Inflammation and Microflora in Cystic Fibrosis: a Pilot Study

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 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 aim of the study is 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 aim is to study the effect of microflora modification on intestinal and extraintestinal inflammation 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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Dietary supplement: placebo; Dietary supplement: Lactobacillus rhamnosus GG

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy
    • Department of Pediatrics University Federico II

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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 (FEV1) 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: probiotic; Lactobacillus rhamnosus GG 5x10^9 colony forming units (CFU)per day	Dietary supplement: Lactobacillus rhamnosus GG; Capsules containing lyophilized 6x10^9 Colony Forming Units (CFU)/die LGG, (60mg) maltodextrin (163 mg), gelatine capsule (75 mg), magnesium stearate (2 mg) 1 capsule/die for 1 month; Other Names: LGG
Placebo Comparator: placebo; maltodextrins	Dietary supplement: placebo; Capsules containing maltodextrin (163 mg), gelatine capsule (75 mg), magnesium stearate (2 mg) 1 cps/die for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modification of intestinal inflammation	Evaluation of intestinal inflammation at baseline and 1 month after treatment	baseline and after 1 month of treatment
change in intestinal microflora composition	Modification of Fluorescent in Situ Hybridization profile of intestinal microflora at baseline and 1 month of treatment	baseline and 1 month after treatment

Collaborators and Investigators

• Sponsor: Federico II University

Publications and helpful links

General Publications

• 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.
• 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.
• Bruzzese E, Callegari ML, Raia V, Viscovo S, Scotto R, Ferrari S, Morelli L, Buccigrossi V, Lo Vecchio A, Ruberto E, Guarino A. Disrupted intestinal microbiota and intestinal inflammation in children with cystic fibrosis and its restoration with Lactobacillus GG: a randomised clinical trial. PLoS One. 2014 Feb 19;9(2):e87796. doi: 10.1371/journal.pone.0087796. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: October 9, 2013
• First Submitted That Met QC Criteria: October 9, 2013
• First Posted (Estimate): October 11, 2013

Study Record Updates

• Last Update Posted (Estimate): October 14, 2013
• Last Update Submitted That Met QC Criteria: October 11, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: children; intestinal inflammation; intestinal microflora
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Inflammation; Cystic Fibrosis
• Other Study ID Numbers: CF pilot