Effect of Lactobacillus Reuteri in Cystic Fibrosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate in patients with cystic fibrosis the effect of Lactobacillus Reuteri (LR) on the rate of respiratory exacerbations and of the infections of both upper respiratory and gastrointestinal tracts.

Detailed Description
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The hallmarks of cystic fibrosis (CF) are recurrent severe and destructive pulmonary inflammation and infection, beginning in early childhood and leading to morbidity and mortality due to respiratory failure. During the disease, most children become colonized with Pseudomonas aeruginosa (PA) and undergo progressive impairment of respiratory function. Therefore, patients colonized with Pseudomonas are at increased risk for pulmonary infections and persistent inflammation and have a decrease in survival rate. In an attempt to reduce the rate and severity of pulmonary exacerbations, children with CF are put on heavy load of antibiotics. Intestinal inflammation is another typical finding in CF patients and gut bacterial overgrowth may be present. Probiotics are live bacteria administered orally, successfully used in children with acute gastroenteritis, as well as in preventing and treating atopic diseases in children. In addition, probiotics have been used as adjuvant therapy in patients with pouchitis and inflammatory bowel diseases. Interestingly, probiotic supplementation is able to reduce the incidence of fever, child care absences, antibiotic prescription and to prevent nosocomial gastrointestinal and respiratory infections. The effect of probiotics may be through improvement of intestinal barrier function and modulation of immune response. The latter mechanism could well explain the clinical effects of probiotics observed in extraintestinal diseases.

Official Title
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Lactobacillus Reuteri Reduces Pulmonary Exacerbations and Upper Respiratory Tract Infections in CF Patients With Mild-to-moderate Lung Disease. LR Administration Might Have a Beneficial Effect on the Disease Course of Cystic Fibrosis.

Conditions
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CYSTIC FIBROSIS

Intervention / Treatment
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* Dietary Supplement: Lactobacillus reuteri
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Forced expiratory volume in the 1st second (FEV1) > 70%. No inhaled or systemic steroids. No anti-inflammatory drugs, antileukotrienes and mast cell membrane stabilizers. No serious organ involvement. Exclusion Criteria: History of pulmonary exacerbation or upper respiratory infection in the previous two months. Changes in medications in the past two months. History of hemoptysis in the past two months.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 42 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lactobacillus reuteri (LR) ATCC55730<br>The tested probiotic, Lactobacillus reuteri, was administered in 5 drops per day (10^10 colony-forming units) for 6 months | Dietary Supplement: Lactobacillus reuteri<br>* Lactobacillus reuteri was administered in 5 drops per day (10^10 colony-forming units) for 6 months.<br>* Other names: (LR) ATCC55730;|
| Placebo Comparator: placebo<br>The placebo was packed in identical bottles, had the same color, weight, smell, and taste of the probiotic formulation for 6 months During the test period, patients were not allowed to consume any other product that contained probiotics or prebiotics | Dietary Supplement: placebo<br>* The placebo was packed in identical bottles, had the same color, weight, smell, and taste of the probiotic formulation, was administered in 5 drops per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Evaluate number of episodes of pulmonary exacerbations that were diagnosed by increase in pulmonary symptoms and airway secretions requiring oral or intravenous antibiotics. | 6 months of observation | 
| Efficacy | Evaluate number of hospital admissions required for pulmonary exacerbations in the two groups. | 6 months of observation | 
| efficacy | Evaluate number of gastrointestinal and upper respiratory tract infections. | 6 months of observation | 
| efficacy | Evaluate duration of hospital admissions required for pulmonary exacerbations in the two groups. | 6 months of observation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy | Evaluate change in qualitative sputum bacteria; | 6 months of observation | 
| efficacy | Evaluate change in fecal calprotectin concentration. | 6 months of observation | 
| efficacy | Evaluate interleukin 8 levels in plasma and induced sputum. | 6 months of observation | 
| efficacy | Evaluate change in quantitative sputum bacteria; | 6 months of observation | 
| efficacy | Evaluate tumor necrosis factor α levels in plasma and induced sputum. | 6 months of observation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cystic fibrosis, probiotics, Lactobacillus reuteri