This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Eventually, we wish to conduct a study of possible pulmonary anti-inflammatory effects of the hydoxyl-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ('statins') in patients with cystic fibrosis. Recent studies document that the 'statin' class of drugs can significantly suppress neutrophilic responses to intra-tracheally administered endotoxin (Etx) in mice. Given the ubiquitous presence of gram negative bacteria and neutrophils in the airways of CF patients, it is reasonable to hypothesize that these drugs may suppress chronic airway inflammation in these patients, which has been linked to progressive deterioration in lung function. It is beleived that the anti-inflammatory effects of statins are primarily due to their inhibitory effects on the prenylation of signaling proteins such as the Rho GTPhases. To our knowledge, this drug class has not yet been tested for efficacy in humans with inflammatory lung disease. However, before embarking upon a complex study with a drug not routinely used in this patient population (since most patients are young, they rarely have elevated cholesterol levels), we first propose to perform a pilot study to document that the drug is effectively absorbed by documenting a pharmacologic effect on cholesterol levels (any possible anti-inflammatory effect may or may not be associated with a cholesterol lowering effect - but the latter would at least document that the drug is absorbed and available pharmacologically).
The Specific Aim, then, for the proposed study is to determine the effect of Lovastatin in an FDA-approved dose of 40 mg bid for 28 d on blood cholesterol levels in five volunteer CF patients. The primary outcome measure for this pilot study, then, will be blood low density lipoprotein-cholesterol (LDL-C) concentrations. Other data (e.g., for safety monitoring) to be acquired include demographic information (age, gender), CF genotype, presence or absence of pancreatic exocrine insufficiency, presence or absence of diabetes, concurrent medications, routine pulmonary spirometry, comprehensive metabolic panel (CMP), creatine kinase (CK), liver function tests (LFTs), and a pregnancy test.
Showing the most recent 10 out of 497 publications
