A B2-agonist as a CFTR activator in CF - Part 2

Phase 1

Conditions: Cystic fibrosis
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: EUCTR2015-001317-28-NL

Lead Sponsor: MC Utrecht

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

-CFTR genotype compound/A455E or compound/R117H
-Already had a rectal biopsy to produce an organoid
-Males and females, aged 18 years or older on the date of informed consent
-Signed informed consent form (ICF)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Severe acute exacerbation or pulmonary infection during last four weeks (needing intravenous treatment and/or systemic corticosteroids)
-Known cardiovascular medical history like cardiac failure, arrhythmias, ischemic cardiac disease, long QT interval syndrome and hypertension
-Known hyperthyroidism, thyrotoxicosis, galactose intolerance, lactase deficiency or glucose-galactose malabsorption
-Haemoglobin A1C (HBA1C) > 45 mmol/mol
-Use of oral B2-agonist one week prior to the start of the study (V1)
-Use of: heart glycoside, high dose sympathomimetics, theophylline, thiazide diuretics or non-selective beta-blockers
-Pregnancy or breastfeeding
-Participation in another drug-investigating clinical study at the start
-Inability to follow instructions of the investigator

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: to evaluate the clinical effect of a long term treatment (8 weeks) with oral B2-agonists in CF patients with residual CFTR function;Secondary Objective: 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). <br>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).<br>;Primary end point(s): Pulmonary function before and after treatment with salbutamol<br>;Timepoint(s) of evaluation of this end point: Before and after treatment with salbutamol

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Fraction exhaled Nitric Oxide (FeNO) and Nasal Nitric Oxide (nNO); <br>•BMI (=weight (in Kg)/Length2 (in cm));<br>•Quality of life (measured with Cystic Fibrosis Questionnaire (CFQ));<br>•Bile salt measurements in plasma and the feces;<br>•Elastase measurements in the feces; <br>•SCC measurements;<br>•Upper and lower airway microbial profiles (microbiome) (conventional culturing, high throughout pyrosequencing (16S rRNA) for bacterial diversity and relative abundance).<br>•Correlation between individual salbutamol induced CFTR function in vitro (organoid-based measurements) and the in vivo treatment effect;<br>•The CFTR stimulating ability of the concentration of salbutamol in the patient’s blood samples, examined by in vitro testing (in the organoid model);;Timepoint(s) of evaluation of this end point: Before and after treatment with salbutamol