Statins To Treat Adult Cystic Fibrosis

Study Overview
=================
Brief Summary
-----------------
Cystic fibrosis (CF) is a lethal genetic condition that affects 30,000 children and adults in the United States. Although CF management has improved substantially over the past two decades, there is still no cure and most patients with CF die before reaching their 50th birthday, largely due to lung failure. There is growing evidence that excess lung and blood inflammation that occurs in response to infections in the lungs cause CF patients to be sicker. Simvastatin is a drug that is used to lower cholesterol, but many researchers have found that this drug may also treat blood and lung inflammation. In this study, we will determine whether or not simvastatin can treat blood and lung inflammation in patients with CF and most importantly determine whether or not it can make these patients feel better and have better lung function.

Detailed Description
-----------------
Study Objectives To determine the effect of 12 weeks of 40 mg once daily simvastatin on general inflammatory molecules, IL-6 and CRP in the blood of CF patients. To determine the effect of simvastatin on LPS-related pathway molecules in the blood. To determine the effect of simvastatin on inflammatory pneumo-proteins in the blood. To determine exacerbation and safety data on statins in preparation for a large phase III trial of statins in CF. Study Endpoints The primary endpoint will be the quantitative changes in serum levels of CRP. Secondary endpoints will include: blood biomarkers IL6, LPS related proteins, LPS, LBP, sCD14 and EndoCAb, and pneumoproteins, SPD and CCL18; and molecules such as TNF-α and IL-1beta; changes in FEV1 over 12 weeks ; and exacerbations over 12 weeks

Official Title
-----------------
The Effect of Simvastatin on Systemic Inflammation in Adult Cystic Fibrosis Subjects: A Pilot Study

Conditions
-----------------
Cystic Fibrosis, Systemic Inflammation

Intervention / Treatment
-----------------
* Drug: Simvastatin
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients of provincial legal age of majority in British Columbia (≥19 years of age); Confirmed diagnosis of CF based on the following criteria: One or more clinical features consistent with the CF phenotype A genotype with identifiable classes I or II CFTR mutations Ability to provide informed consent. Clinically stable at enrollment as assessed by the treating physician. Ability to comply with medication use, study visits and study procedures, such as spirometry, and venipunctures. Exclusion Criteria: Allergy or clinical reaction to simvastatin. The following abnormal lab values within the last six months or at screening: AST/ALT > 1.5 ULN, CK > 1.5 ULN, and eGFR < 40ml/min/1.73m2. Use of intravenous antibiotics or oral quinolones within 14 days of screening. With the exception of Azithromycin the use of oral antibiotics including prophylactic antibiotics (e.g., augmentin, tetracycline, cloxacillin, cephalosporins, trimethoprim/sulfamethoxazole) within 14 days of screening. Initiation of high dose ibuprofen, dornase alpha, hypertonic saline or aerosolized antibiotics within 30 days of screening. On medications that are known to have potential serious interactions with simvastatin (as listed on page 10 of this protocol). Use of systemic corticosteroids within 30 days of screening. Investigational drug use within 30 days of screening. Other major organ dysfunction excluding pancreatic dysfunction. History of lung transplantation or currently on lung transplant list. Pregnant, breast feeding, or if post-menarche female, unwilling to practice birth control during participation in the study. Chronic users of niacin, azole antifungals (itraconazole, ketoconazole, voriconazole), telithromycin, fibric acid derivatives, HIV protease inhibitors, amiodarone, digoxin and/or cyclosporine (to decrease the risk of statin-related myotoxicity). Patients who are colonized or infected with Burkholderia cepacia complex are excluded.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simvastatin 40 mg/d<br>simvastatin 40 mg per day taken orally | Drug: Simvastatin<br>* simvastatin 40 mg per day orally for 12 weeks.<br>|
| Placebo Comparator: Sugar pill<br> | Drug: placebo<br>* placebo 1 tablet once daily for 12 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-reactive protein | The difference in the change in plasma C-reactive protein concentrations from baseline to 12 weeks of treatment between those randomized to simvastatin 40 mg/d and those randomized to placebo | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in forced expiratory volume in one second (FEV1) | The differences in the above parameters over 12 weeks between those assigned to simvastatin 40 mg/d and those assigned to placebo. | 12 weeks | 
| Changes in exacerbation rates | The differences in the above parameters over 12 weeks between those assigned to simvastatin 40 mg/d and those assigned to placebo. | 12 weeks | 
| Changes in blood pro-inflammatory markers such as IL-6, TNF, IL-1beta, LPS, LBP, sCD14, EndoCAB, SP-D, CCL-18) | The differences in the above parameters over 12 weeks between those assigned to simvastatin 40 mg/d and those assigned to placebo. | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cystic fibrosis, adult cystic fibrosis