Cystic fibrosis patients with F508del-CFTR in homozygous or compound heterozygous with Class I or II mutations
Conditions
Interventions
Trade Name: Cystagon
Product Name: Cysteamine bitartrate (Cystagon)
Product Code: EMEA/H/C/000125
Pharmaceutical Form: Capsule
Sponsors
European Institute for Cystic Fibrosis Research (IERFC)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Diagnosis of cystic fibrosis by sweat test with chloride level=60 mEq/l and confirmed by genetic analysis in order to search cystic fibrosis F508del-CFTR homozigotic mutation or F508del-CFTR combined mutations of class I and II - males or females aged at least 6 years old. - fertile females should accept a contraceptive method. - FEV1 =40% as compared to expected value for age and sex. - At least 2 sweat tests within the 3 months before Meeting 1 to establish the interindividual variation of chloride level in the sweat. - Informed agreement - All subjects must be able to understand the aim of the study Are the trial subjects under 18? yes Number of subjects for this age range: 60 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Treatment with glucocorticoids per os or via inhalationat Meeting 1 or within 4 weeks before meeting 1. - Treatment with oxygen, over day or over night. - Other experimental drugs. - Hypersensitivity (local or general) to cysteamine or penicillamine. - Modifications in the therapy with macrolides, ant-asmatic, mucolytic drugs, Dornase alfa, and/or FANS, DHA within 28 days before Meeting 1. However, ita can be accepted the use of some drugs (for example FANS). - Lung/hepatic/other organ transplantation. - Kidney or hepatic alterations at Meeting 1: -AST, ALT > 5 fold normal value . - Creatinine > 2 fold normal value (ULN). - Pregnancy - Nursing. - No contraceptive method. - Neurologic and psychiatric pathologies that, on the basis of the Researcher experience, could interfere with protocol
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): In the sputum it will be evaluated a) the number of pro-inflammatory cells; b) IL-8 and neutrophilic elastase levels as compared to the same patient at the beginning of the study.;Timepoint(s) of evaluation of this end point: After 4, 8, 12, 20, 28, 36, 44 weeks from the beginning of the study | — |
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: not applyable;Timepoint(s) of evaluation of this end point: After 4,8, 12, 20, 28, 36, 44 weeks;Main Objective: To investigate the effectiveness in the functional rescue of CFTR protein and the safety in the use of proteostasis regulator (cysteamine bitartrate) in association with a flavonoid (epigallocatechine gallate) with the aim to strenghten the beneficial effects of cysteamine on the F508del-CFTR protein at the plasma membrane level, in cystic fibrosis patients with F508del-CFTR in homozygous or compound heterozygous with Class I or II mutations aged at least 6 years old. The study has been temporally extended in order to asses the therapeutic efficacy as well as tolerability of cysteamine bitartrate in patients either patient homozygotes or heterozigotes for F508del-CFTR;Primary end point(s): Sweat test: reduction of chloride of at leastl 15% as compared to the same patient at the beginning of the study. Brushing of the nose: experiments will be performed to a) evaluate the chloride channel activity of CFTR by SPQ technique; b) the expression of pro-inflammatory cytokines (TNFalpha, IL-8) by Polymerase Chain Reaction (PCR) as compared to the same patient at the beginning of the study. | — |
Countries
Italy
Contacts
Public ContactDept. of Translational Medicine
AOU Federico II, Clinical Department of Pediatrics
Outcome results
None listed