Amitriptyline reduces ceramide concentrations in bronchial epithelial cells and reduces cell death and reduces the deposition of DNA on the respiratory epithelium. This reduction promotes the elimination of P. aeruginosa bacteria from the lung. As a result, treatment normalizes inflammation in CF lungs. Amitriptyline thus reduces systemic and local inflammation. Because of these effects, amitriptyline increases lung function in CF patients.
Conditions
Interventions
Trade Name: Amitriptylin-CT
Product Name: Amitriptyline
Pharmaceutical Form: Capsule
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use
Sponsors
University Hospital Tuebingen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Cystic Fibrosis is verified; 2. Patient is older than 12 years; 3. Patients weight is more than 35 kg; 4. FEV1 is higher than 25% and lower than 100% (two times in 3 months); 5. The patients lung is colonised with bacteria; 6. No acute pulmonal illness is present; 7. Lung function testing is possible; 8. A full course of therapy is possible without any restrictions; 9. Informed consent is given. Are the trial subjects under 18? yes Number of subjects for this age range: 15 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 87 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. FEV1 in screening and baseline differs more than 10%; 2. Clinicial detoriation is present (exacerbation symptoms); 3. Change of CRP of more than 50% in screening period; 4. Glaucoma, seizures, heart insufficiency or major depression is pre-sent; 5. Intravenous antibiotic treatment was necessary for the last 2 weeks prior to the trial; 6. High dose steroid therapy; 7. On-therapy of tobramycine in the last 2 weeks; 8. Involvement of the patient in another study; 9. Pregnancy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Difference in mean absolute differences in percent predicted FEV1 between verum and placebo at week 8 compared to baseline;Timepoint(s) of evaluation of this end point: at week 8 compared to baseline;Main Objective: Difference in absolute FEV1 % predicted between verum and placebo at week 8 compared to baseline;Secondary Objective: 1. Maintenance of the reached FEV1 in the verum group between week 8 and week 16. 2. Absolute and relative FEV1 as % predicted after 4, 8, 12 and 16 weeks compared to baseline, if not primary; 3. All other lung function parameters (FVC, MEFs and lung clearance index-LCI); 4. Concentration of Ceramide in sputum; 5. Concentration of pro-inflammatory cytokines, change of anti-inflammatory IL-10 in tracheal mucus; 6. Content of DNA and granulocyte concentration in sputum; 7. Bacterial colonisation in sputum; 8. Number of exacerbations of pulmonary symptoms; 9. Incidence of discontinuation of treatment because perceived side ef-fects. 10. Changes in body weight 11. Quality of life questionnaire adapted to CF | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Maintenance of the reached FEV1 amount in the verum group between week 8 and week 16 re-garding a difference up to 4,2% as being equivalent. - Absolute and relative FEV1 increase after 4, 8, 12 and 16 weeks compared to baseline, if not pri-mary. - All other lung function parameters (FVC, MEF25, MEF50, MEF75, MEF25-75, LCI) after 4, 8, 12 and 16 weeks compared to baseline. - Concentration of Ceramide in sputum after 8 and 16 weeks compared to baseline. - Concentration of pro-inflammatory cytokines (IL-6, IL-8, TNFa), change of anti-inflammatory IL-10 in tracheal mucus after 4, 8, 12 and 16 weeks compared to baseline. - Content of DNA and granulocyte concentration in sputum after 4, 8, 12 and 16 weeks compared to baseline. - Chronic bacterial colonisation (cumulative Cfu) in sputum after 4, 8, 12 and 16 weeks compared to baseline. - Number of exacerbations of pulmonary symptoms (pulmonary infections treated with antibiotics) after 8 and 16 weeks compared to baseline. - Incidence of discontinuation of treatment due to perceived side effects. - Question 18 of quality of life questionnaire adapted to CF after 8 and 16 weeks compared to baseline. ;Timepoint(s) of evaluation of this end point: Each after 4, 8, 12 and 16 weeks compared to baseline. | — |
Countries
Germany
Contacts
Public ContactDr.med. Andreas Hector
University Children's Hospital, CPCS
Outcome results
None listed