Statins To Treat Adult Cystic Fibrosis

NCT ID: NCT01092572

Last Updated: 2014-01-30

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2010-05-31

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

Conditions

Cystic Fibrosis; Systemic Inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Simvastatin 40 mg/d

simvastatin 40 mg per day taken orally

Group Type: EXPERIMENTAL

Simvastatin

Intervention Type: DRUG

simvastatin 40 mg per day orally for 12 weeks.

Sugar pill

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo 1 tablet once daily for 12 weeks

Interventions

Simvastatin

simvastatin 40 mg per day orally for 12 weeks.

Intervention Type: DRUG

placebo

placebo 1 tablet once daily for 12 weeks

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Man, MD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Other Identifiers

CF-Man-Statin-1

Identifier Type: -

Identifier Source: org_study_id