Bronchodilcation as a CFTR activator in CF

Phase 1

Conditions: Cystic Fibrosis
Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

Registration Number: EUCTR2014-000057-37-NL

Lead Sponsor: niversity Medical Centre 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
-CFTR measurement available in intestinal biopsies
-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 10
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 (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
-HBA1C > 45 mmol/mol
-Use of 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 or within 1 month prior to 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 investigate the clinical response on treatment with a B2-agonist in a CF-patient with residual CFTR function by examining change in nasal potential difference (NPD) and sweat chloride concentration (SCC). ;Secondary Objective: 1.To compare the efficacy of B2-agonist treatment per inhalation with oral B2-agonist by measuring the NPD and SCC. <br>2.To investigate the correlations between individual B2-agonist-induced CFTR function in vitro (using organoid-based measurements) and treatment effect in vivo (by measuring the NPD and SCC)<br>3.To assess whether the dosage of B2-agonist used in the clinical study is sufficient to stimulate CFTR function, by testing the CFTR stimulating effect of patients’ blood samples in vitro, on autologous organoid cultures. <br> <br>;Primary end point(s): NAsal Potential Difference measurement<br>Sweat Chloride Concentration;Timepoint(s) of evaluation of this end point: At 4 studyvisits endpoints will be measured.<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): NPD<br>SCC<br>Blood sample<br>CFTR function in organoids;Timepoint(s) of evaluation of this end point: Also measured at all 4 studyvisits