The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function

Study Overview
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Brief Summary
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Inhalation treatment with mucolytics is one of the cornerstones of CF treatment for respiratory problems. The efficacy of inhalation treatment with recombinant DNAse and hypertonic saline is well established. The North American CF foundation reported that there is insufficient evidence for or against the chronic use of inhaled N-Acetylcysteine (NAC) to improve lung function and reduce exacerbations . In vitro tests proved the positive effect of NAC on sputum rheology . Evidence based research however on the in vivo effect of NAC on visco-elasticity and lung function is rare. There are only three randomized controlled clinical trials on nebulised NAC, none of them showing a statistically significant or clinically relevant beneficial effect. Nevertheless at least in Europe for many years inhalation treatment with NAC is advised. Because of the disgusting sulphur odour, many patients are reluctant to use this inhalation medication. We intend to start an open placebo controlled in vivo cross-over study to evaluate the effect of Acetyl cysteine compared to normal saline on the sputum visco-elasticity and on the short term effect on lung function. Sputum producing CF-patients, able to perform lung function tests will be enrolled. Sputum viscoelasticity will be measured by a controlled-stress rheometer (AR 1000-N; TA-Instruments, Ghent, Belgium) at 20° C, using a cone-plate geometry 8. Lung function measurement (FVC, FEV1, FEF 25-75) will be done in a Masterlab body plethysmograph (Jaeger®) Sputum samples will be collected before lung function test on a regular control visit. Three ml of NAC or 4 ml of normal saline will be inhaled, afterwards a second sputum sample will be collected and a control lung function test will be performed. Visco-elasticity measurements will be done on sputum samples before and after inhalation of NAC or normal saline. Patients will continue to inhale N-acetylcysteine or normal saline two times per day for one month. After one month a control lung function and a third sputum sample will be collected, visco-elasticity and lung function will be measured and compared to the initial values in both groups and between groups. After a wash-out period of normal saline inhalations during 2 weeks in both groups, patients in the initial control group will be asked to switch to inhalation of 3 ml of NAC two times per day and the former NAC group will continue to inhale two times 4 ml of normal saline during four weeks. After one month the same measurements of visco-elasticity and lung function tests will be done.

Official Title
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The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function.

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Acetylcysteine
* Drug: normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who can perform lung function tests and who can produce sputum (> 5 years of age) (Fe)males between 6-64 years Exclusion Criteria: Patients on the waiting lists for lung transplant. Pregnancy or breast feeding Patients can not take part in another 'inhalation'trial for Cystic Fibrosis

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 64 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: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetylcysteine<br>Inhalation with N-Acetylcysteine | Drug: Acetylcysteine<br>* Inhalation with N-Acetylcysteine<br>|
| Placebo Comparator: normal saline<br>Inhalation with normal saline solution | Drug: normal saline<br>* Inhalation with normal saline solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in visco-elasticity and lung function. |  | after one dose of N-acetylcystein compared to normal saline | 
| Changes in visco-elasticity and lung function. |  | after one month of two doses per day of N-acetylcysteine compared to normal saline. |