Clinical trial NCT01092572: Statins To Treat Adult Cystic Fibrosis
Official title: The Effect of Simvastatin on Systemic Inflammation in Adult Cystic Fibrosis Subjects: A Pilot Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Cystic Fibrosis
Systemic Inflammation
Keywords: cystic fibrosis
adult cystic fibrosis
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2010-03-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

1. 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.
2. To determine the effect of simvastatin on LPS-related pathway molecules in the blood.
3. To determine the effect of simvastatin on inflammatory pneumo-proteins in the blood.
4. 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:

1. 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;
2. changes in FEV1 over 12 weeks ; and
3. exacerbations over 12 weeks

Eligibility criteria: Inclusion Criteria:

1. Patients of provincial legal age of majority in British Columbia (≥19 years of age);
2. 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
3. Ability to provide informed consent.
4. Clinically stable at enrollment as assessed by the treating physician.
5. Ability to comply with medication use, study visits and study procedures, such as spirometry, and venipunctures.

Exclusion Criteria:

1. Allergy or clinical reaction to simvastatin.
2. 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.
3. Use of intravenous antibiotics or oral quinolones within 14 days of screening.
4. 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.
5. Initiation of high dose ibuprofen, dornase alpha, hypertonic saline or aerosolized antibiotics within 30 days of screening.
6. On medications that are known to have potential serious interactions with simvastatin (as listed on page 10 of this protocol).
7. Use of systemic corticosteroids within 30 days of screening.
8. Investigational drug use within 30 days of screening.
9. Other major organ dysfunction excluding pancreatic dysfunction.
10. History of lung transplantation or currently on lung transplant list.
11. Pregnant, breast feeding, or if post-menarche female, unwilling to practice birth control during participation in the study.
12. 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).
13. Patients who are colonized or infected with Burkholderia cepacia complex are excluded.

Primary outcomes:
measure: C-reactive protein
timeFrame: 12 weeks
Secondary outcomes:
measure: Changes in forced expiratory volume in one second (FEV1)
timeFrame: 12 weeks
measure: Changes in exacerbation rates
timeFrame: 12 weeks
measure: Changes in blood pro-inflammatory markers such as IL-6, TNF, IL-1beta, LPS, LBP, sCD14, EndoCAB, SP-D, CCL-18)
timeFrame: 12 weeks
Other outcomes:
Locations:
Study officials:
affiliation: University of British Columbia
name: Paul Man, MD
role: PRINCIPAL_INVESTIGATOR
References: