A B2-agonist as a CFTR activator in CF
Part II

Objective: Primary objective of this study is to evaluate the clinical effect of a long term treatment (8 weeks) with oral B2-agonists in CF patients with residual CFTR function, especially on lung function (spirometry and airway resistance).

Secondary objectives are to:

1. Evaluate the correlations between individual B2-agonist-induced CFTR function in vitro (organoid-based measurements) and the long term clinical treatment effect (eg. lung function and airway resistance).

2. Assess the effect of the salbutamol concentration in the blood on CFTR function in the background of patient specific parameters. We will do this by examining the CFTR-stimulating potential of the patients’ blood in vitro (in the organoid model).

Study design: A multicentre open label intervention study.

Study population: Adults with Cystic Fibrosis with a compound/A455E or compound/ R117H mutation and proven residual CFTR function in vitro. We aim to include 20 patients.

Intervention: After baseline measurements all patients will receive oral Salbutamol during 8 weeks.

Main study parameters/endpoints: Pulmonary function (spirometry and airway resistance measured with the bodybox and Rint)

• Before and after treatment with salbutamol

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients participating in this study will be treated at home and will visit the hospital for two study visits. Salbutamol has been used in clinical practice for over decades in patients with asthma and no serious side effects have been reported. Therefore we do not expect serious problems or side effects during this study. We expect to see a clear clinical effect of long term treatment with oral salbutamol. When our hypothesis is confirmed, this is a major benefit for the patient. Not only during the study period but also for their further treatment. When this study confirms our hypothesis that organoids can predict clinical responders, this is a major benefit not only for the CF population but also for the individual patient. With the use of organoids we will then be able to generate optimal treatment strategies for individuals based on (combinations of) current and future drugs with only limited patient discomfort.

Long term use (8 weeks) of oral B2-agonists increases CFTR function and improves disease parameters in patients with CF with a residual CFTR function.

Before and after treatment with oral salbutamol

4dd4mg salbutamol oral