Probiotics in Cystic Fibrosis

NCT01956916 | Completed Phase 3 DMC

• 2 other identifiers: CF0012009-011289-27
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 5

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.

Conditions

Cystic Fibrosis

Keywords

Pulmonary exacerbation; Inflammation; Intestinal microbiota

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Change in the incidence of hospital admission from baseline to 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))

  every six months up to 18 months

Other Outcomes (3)

• Change in the incidence of abdominal pain episodes from baseline to 12 months of treatment

  every six months up to 18 months

• Change in systemic inflammation from baseline to 12 months of treatment

  At baseline and after 12 months of treatment

• Change of intestinal microflora composition from baseline to 12 months of treatment

  baseline and 12 months after treatment

Study Arms (2)

Probiotics

EXPERIMENTAL

Capsules containing lyophilized 6x10\^9 Colony Forming Units (CFU)/die of Lactobacillus rhamnosus GG (LGG)

Dietary Supplement: Lactobacillus rhamnosus GG

Placebo

PLACEBO COMPARATOR

Capsules containing maltodextrin

Dietary Supplement: placebo

Interventions

Lactobacillus rhamnosus GG DIETARY_SUPPLEMENT

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

Also known as: LGG

Probiotics

placebo DIETARY_SUPPLEMENT

Capsules containing maltodextrin (163 mg), gelatine capsule (75 mg), magnesium stearate (2 mg) 1 cps/die for 12 months

Placebo

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Federico II University: lead

Study Sites (5)

- Department of Paediatric Medicine, CF Center, "A. Meyer" Children's Hospital

Florence, Italy

Location

Dipartimento di Pediatria - Università Di Messina

Messina, Italy

Location

Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena

Milan, Italy

Location

Università degli studi di Napoli "Federico II"

Napoli, Italy

Location

Ospedale "Bambino Gesù" - Roma

Rome, Italy

Location

Related Publications (5)

• 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.

  PMID: 17360077 BACKGROUND

• 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.

  PMID: 15379842 BACKGROUND

• 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.

  PMID: 10709733 BACKGROUND

• 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.

  PMID: 19543116 BACKGROUND

• 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.

  PMID: 27810876 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis; Inflammation

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor Of Pediatrics

Study Record Dates

• First Submitted: September 23, 2013
• First Posted: October 8, 2013
• Study Start: October 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: September 23, 2015

Record last verified: 2015-09

Locations

IT (5)