Statins To Treat Adult Cystic Fibrosis (CFStatin)

University of British Columbia

Status and phase

Withdrawn

Phase 2

Phase 1

Conditions

Systemic Inflammation

Cystic Fibrosis

Treatments

Drug: Simvastatin

Drug: placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT01092572

CF-Man-Statin-1

Details and patient eligibility

About

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.

Full 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

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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:
1. One or more clinical features consistent with the CF phenotype
2. 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.