Anti-Inflammatory Pulmonal Therapy of CF-Patients With Amitriptyline and Placebo
Status:
Completed
Trial end date:
2007-07-01
Target enrollment:
Participant gender:
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
Details
Lead Sponsor:
University Hospital Tuebingen
Treatments:
Amitriptyline Amitriptyline, perphenazine drug combination Anti-Inflammatory Agents