Anti-Inflammatory Pulmonal Therapy of CF-Patients With Amitriptyline and Placebo

• Status: Completed
• Trial end date: 2007-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Our data indicate that the CFTR-molecule functions as a transporter for sphingosine-1-phosphate and sphingosine or regulates the uptake of these sphingolipids by epithelial cells. The disturbed uptake of sphingosine and sphingosine-1-phosphate over the cell membrane results in an accumulation of ceramide in the cell membrane, which finally triggers a pro-inflammatory and pro-apoptotic status in the respiratory tract of cystic fibrosis patients. Amitriptyline reduces the cera-mide levels in the lung tissue, normalises the activity of cytokines and prevents constitutive cell death of epithelial cells observed in CFTR-deficient mice. Most important, amitriptyline prevents pulmonary infections of CFTR-deficient mice with P. aeruginosa. These effects of amitriptyline may result in an improved lung function of cystic fibrosis patients.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Tuebingen
• Treatments: Amitriptyline; Amitriptyline, perphenazine drug combination; Anti-Inflammatory Agents

Criteria

Inclusion Criteria:

1. Cystic Fibrosis is proved

2. The patient are older than 18 years (<50 years)

3. No sec discrimination

4. The patient is pulmonal colonized with bacteria

5. Signs of pulmonary exacerbation are not present

6. A full course of therapy is possible without any restrictions

7. Lung function measurement is possible

Exclusion Criteria:

1. Poor metabolizer for amitriptyline (CYP2D6 genotyping)

2. Glaucoma, seizures, heart insufficiency or depression is present

3. Signs of acute pulmonary illness (bronchial or tracheal stenosis, tuberculosis, thorax trauma, acute pneumonia, pneumothorax, bronchial haemorrhage, ARDS) are present

4. intravenous antibiotic treatment was necessary in the last 4 weeks

5. Involvement of the patient in another study

6. Pregnancy