No detectable improvements in cystic fibrosis transmembrane conductance regulator by nasal aminoglycosides in patients with cystic fibrosis with stop mutations.
Study design (if review, criteria of inclusion for studies)
multicenter randomized, double-blinded, crossover and parallel study; two cohorts of patients with CF.
Participants
11 CF patients with stop mutations were enrolled in a crossover fashion to receive each drug; 18 CF patients without stop mutations were randomized 1:1 in a parallel fashion to receive one drug.
Interventions
gentamicin and tobramycin administered over a 28-d period
Outcome measures
Primary aim was to test whether nasally administered gentamicin or tobramycin could suppress premature stop mutations in CFTR, resulting in full-length, functional protein. A secondary objective was to obtain data to aid in the design of multicenter trials using the nasal potential difference as a study endpoint.
Main results
After demonstration of drug delivery, neither aminoglycoside produced detectable changes in nasal ion transport or CFTR localization in brushed cells from either study group. These results with first-generation suppressive agents suggest the need for improved drug delivery methods and/or more potent suppressors of nonsense mutations to confer CFTR correction in subjects with CF heterozygous for nonsense mutations.
Authors' conclusions
The study provides valuable information on parameters of the nasal potential difference measurements for use in future multicenter clinical trials.