Taste Receptors Regulation in CF Patients

Study Overview
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Brief Summary
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The project is intended to be realised in two phases. In the first stage, a case control study will be performed. In the second phase, double-blind, placebo controlled cross-over study will be conducted. The first stage it to compare innate immunity activation and Pseudomonas aeruginosa (Pa) expression between Pa positive and negative patients. In the second phase the effects of inhaled lactizole- TAS3R inhibitor will be assessed.

Detailed Description
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Three visits have been planned during the entire study. During the first visit, all patients included in the study will have the following procedures: questionnaire tests, lung function tests, taste perception tests (gustometry) and exfoliative cytology of the nasal mucosa. Patients with confirmed Pseudomonas aeruginosa presence in the airways will be randomly assigned to the Lactizole-Placebo group and the Placebo-Lactizole group, with a recommendation to take laktizol (3 ml) for 3 weeks at the concentration determined during the preliminary examination, in the nebulization 2 times per day) or placebo (3ml 0.9% NaCl solution in nebulization 2 once a day). The first nebulization of the solution issued during the visit will take place during the visit; each patient will undergo a clinical and spirometric assessment after 20 minutes of observation from completed nebulization. During the second visit (after 4 weeks from visit 1), the first visit procedures will be repeated for all patients. Patients in the Lactizole-Placebo group will be recommended to take a placebo for 4 weeks (3 ml of 0.9% NaCl solution in nebulization 2 once a day); on the other hand, patients from the Placebo-Lactizole group will be advised to take lactisol for 4 weeks (3 ml of the solution in the concentration determined during the preliminary examination, in the nebulization 2 once a day). The first nebulization of the solution issued during the visit will take place during the visit; each patient will undergo a clinical and spirometric assessment after 20 minutes of observation from completed nebulization. During the third visit (after 4 weeks from visit 2), the first visit procedures will be repeated for all patients.

Official Title
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The Effects of Taste Receptors Regulation in Upper Airway Innate Immunity of CF Patients

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Dietary Supplement: lactizole nebulization
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ulmonary manifestations of cystic fibrosis Exclusion Criteria: first positive result of inoculation from the airways, which according to the standard is associated with the need for antibiotic therapy contraindication to a biopsy of the nasal mucosa exacerbation requiring antibiotics diabetes, exposure to tobacco smoke other chronic diseases and clinical conditions which, according to the researcher, may influence the assessed parameters and the course of the study. Temporary exclusion criteria - acute respiratory infection within 2 weeks from 1, 2 and 3 visits of the study.

Ages Eligible for Study
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Minimum Age: 6 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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: lactizole-placebo<br>A group of patients who will receive 3ml lactizole solution (150ppm) in nebulization twice a day for 4 weeks , and then for the next 4 weeks they will receive 2 times a day 3ml 0.9% NaCl solution in nebulization | Dietary Supplement: lactizole nebulization<br>* Lactizole is generally recognized as safe: GRAS Flavor and Extract Manufacturers Association ( numer: 3773 ) Lactizole solution for nebulization was calculated based on dose-response curves; 150ppm was chosen as minimal effective (decreased sweet taste perception) and safety ( lack of FEV1 changes after nebulization)<br>Other: Placebo<br>* 0.9% NaCl solution in nebulization<br>|
| Active Comparator: placebo-lactizole<br>A group of patients who will receive 2 times a day for 4 weeks (0.9% NaCl solution in nebulization) for 4 weeks and will receive 3ml of lactizole solution (150ppm) in nebulization 2 times a day for 4 weeks | Dietary Supplement: lactizole nebulization<br>* Lactizole is generally recognized as safe: GRAS Flavor and Extract Manufacturers Association ( numer: 3773 ) Lactizole solution for nebulization was calculated based on dose-response curves; 150ppm was chosen as minimal effective (decreased sweet taste perception) and safety ( lack of FEV1 changes after nebulization)<br>Other: Placebo<br>* 0.9% NaCl solution in nebulization<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Pseudomonas aeruginosa abundance | Decrease of abundance of P. aeruginosa in throat swabs after nebulized lactizole . intervention. PCR testing for the presence of Pseudomonas aeruginosa genetic material (FTD Bacterial pneumoniae-HAP, Fast-track diagnostics Ltd., Malta) | Change from Baseline after 4 weeks of the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in cystic fibrosis symptoms | Questionnaire (standardized questionnaire to assess the degree of control of cystic fibrosis symptoms). Polish version of the Cystic Fibrosis Quality of Life Questionnaire (CFQoL) will be used | Change from Baseline after 4 weeks of the intervention | 
| Change from Baseline in Lung function test | Lung function test: spirometry will be performed in accordance with ERS / ATS standards | Change from Baseline after 4 weeks of the intervention | 
| Change from Baseline in Taste perception | Taste perception testing (gustometry): quantitative evaluation using a standardized TSTs diagnostic tool (Taste Strips, Burghart, Wedel, Germany | Change from Baseline after 4 weeks of the intervention | 
| Change from Baseline in Nasal ILC1, 2 and 3 cells | Nasal mucosa samples (Rhino-probe, ASI, Arlington, Texas). The assessment of the nasal mucosa material will include: percentage of ILC1, 2 and 3 cells (immunophenotyping and measurement by flow cytometry) | Change from Baseline after 4 weeks of the intervention | 
| Change from Baseline in Nasal cytokines expression | Nasal mucosa samples (Rhino-probe, ASI, Arlington, Texas). The assessment of the nasal mucosa material will include: mRNA expression for: Muc5b, Muc5ac, Beta-defensine, T1R3, T2Rs, selected cytokines (qPCR technique using self-designed primers) | Change from Baseline after 4 weeks of the intervention |