Genistein as an add-on treatment for CF?

• Register: EUCTR
• Last refreshed on: 8 May 2017
• Main ID: EUCTR2016-001619-19-NL
• Date of registration: 27/03/2017
• Prospective Registration: Yes
• Primary sponsor: UMC Utrecht
• Public title: Genistein as an add-on treatment for CF?
• Scientific title: Genistein as an add-on treatment for CF? -
• Date of first enrolment: 27/03/2017
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001619-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: Gitte Berkers
• Affiliation: UMC Utrecht

• Name: Gitte Berkers
• Affiliation: UMC Utrecht

Key inclusion & exclusion criteria

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

Exclusion criteria:
• Use of genistein or curcumin at start or within four weeks prior to start of the study;
• Severe acute exacerbation or pulmonary infection during last four weeks (needing intravenous treatment and/or systemic corticosteroids);

• (History of) hypothyroidism;
• Women who are trying to become pregnant or are pregnant or breastfeeding;
• Women with estrogen receptor-positive tumors;
• Postmenopausal women on tamoxifen therapy for estrogen-responsive breast cancer;
• Participation in another drug-investigating clinical study at the start or within four weeks prior to the start;
• Inability to follow instructions of the investigator.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Cystic Fibrosis

Intervention(s)

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

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 8 weeks

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.

Secondary Outcome(s)

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

Secondary ID(s)

TRIO-2016

Source(s) of Monetary Support

ZonMw

NCFS