Genistein as an add-on treatment for CF?

INTERVENTION: Product Name: Genistein Pharmaceutical Form: Capsule INN or Proposed INN: genistein CAS Number: 446‐72‐0 Other descriptive name: GENISTEIN Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 48.5‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use CONDITION: Cystic Fibrosis ; Therapeutic area: Diseases [C] ‐ Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] PRIMARY OUTCOME: Main Objective: Primary objective is to investigate whether a further gain in efficacy of oral Ivacaftor treatment can be reached by co‐supplementation of genistein, as suggested by their highly synergistic action in intestinal organoids. Primary end point(s): The main study parameter is pulmonary function (%FEV1) measured before and after the use of genistein and before and after the use of placebo. Secondary Objective: 1: to evaluate the correlations between individual Ivacaftor genistein induced CFTR function in vitro (organoid‐based measurements) and the in vivo treatment effect. ; 2: to evaluate the correlation between serum levels of Ivacaftor and genistein and the in vivo treatment effect.; Timepoint(s) of evaluation of this end point: 8 weeks SECONDARY OUTCOME: Secondary end point(s): Secondary endpoints to evaluate in vivo effect: ; ; • Sweat chloride concentration (SCC), before and after the use of genistein and placebo;; • Airway resistance (Rint and bodybox), before and after the use of genistein and placebo;; • BMI (=weight (in Kg)/Length2 (in cm)) before and after the use of genistein and placebo;; • Quality of life (measured with CFQ‐questionnaire) before and after the use of genistein and placebo;; • Elastase measurements in the feces before and after the use of genistein and placebo; ; • The CFTR stimulating ability of the concentration of genistein in the patient’s blood samples, examined by in vitro testing (in the organoid model). We will also determine the plasma levels of genistein;; Timepoint(s) of evaluation of this end point: 8 weeks INCLUSION CRITERIA: • CFTR genotype associated with residual CFTR function; • Already had a rectal biopsy to produce an organoid; • Use of Ivacaftor; • Male and female patients, aged 6 years or older on the date of informed consent; • Signed informed consent form (IC). Are the trial subjects under 18? yes Number of subjects for this age range: 10 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