Probiotics in Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01956916
• Other study ID #: CF001
• Secondary ID: 2009-011289-27
• Status: Completed
• Phase: Phase 3
• First received: September 23, 2013
• Last updated: September 22, 2015
• Start date: October 2010
• Est. completion date: December 2014

Study information

• Verified date: September 2015
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Italian Agency of Drugs - AIFA
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 18 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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

Locations

Country	Name	City	State
Italy	- Department of Paediatric Medicine, CF Center, "A. Meyer" Children's Hospital	Florence
Italy	Dipartimento di Pediatria - Università Di Messina	Messina
Italy	Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena	Milano
Italy	Università degli studi di Napoli "Federico II"	Napoli
Italy	Ospedale "Bambino Gesù" - Roma	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Federico II University

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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. — View 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. Epub 2007 Mar 13. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in the incidence of abdominal pain episodes from baseline to 12 months of treatment	The incidence of abdominal pain episodes 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	No
Other	Change in systemic inflammation from baseline to 12 months of treatment	Assessment of intestinal microflora composition is performed 2 times. First time at randomization (placebo/LGG), second time at the end of 12 months of treatment.	At baseline and after 12 months of treatment	No
Other	Change of intestinal microflora composition from baseline to 12 months of treatment	Assessment of intestinal microflora composition is performed 2 times. First time at randomization (placebo/LGG), second time at the end of 12 months of treatment.	baseline and 12 months after treatment	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No