The Effect of Inhaled N-Acetylcysteine Compared to Normal Saline on Sputum Rheology and Lung Function
Status:
Terminated
Trial end date:
2010-12-01
Target enrollment:
Participant gender:
Summary
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.