Statins To Treat Adult Cystic Fibrosis - Full Text View

Purpose

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.

Condition	Intervention	Phase
Cystic Fibrosis Systemic Inflammation	Drug: Simvastatin Drug: placebo	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	The Effect of Simvastatin on Systemic Inflammation in Adult Cystic Fibrosis Subjects: A Pilot Study

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Simvastatin

Genetic and Rare Diseases Information Center resources: Cystic Fibrosis

U.S. FDA Resources

Further study details as provided by University of British Columbia:

Primary Outcome Measures:

C-reactive protein [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
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

Secondary Outcome Measures:

Changes in forced expiratory volume in one second (FEV1) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
The differences in the above parameters over 12 weeks between those assigned to simvastatin 40 mg/d and those assigned to placebo.
Changes in exacerbation rates [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
The differences in the above parameters over 12 weeks between those assigned to simvastatin 40 mg/d and those assigned to placebo.
Changes in blood pro-inflammatory markers such as IL-6, TNF, IL-1beta, LPS, LBP, sCD14, EndoCAB, SP-D, CCL-18) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
The differences in the above parameters over 12 weeks between those assigned to simvastatin 40 mg/d and those assigned to placebo.


Enrollment:	0
Study Start Date:	May 2010
Study Completion Date:	May 2010
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Simvastatin 40 mg/d simvastatin 40 mg per day taken orally	Drug: Simvastatin simvastatin 40 mg per day orally for 12 weeks.
Placebo Comparator: Sugar pill	Drug: placebo placebo 1 tablet once daily for 12 weeks

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

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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:
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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01092572

Sponsors and Collaborators

University of British Columbia

Investigators


Principal Investigator:	Paul Man, MD	University of British Columbia

More Information


Responsible Party:	University of British Columbia
ClinicalTrials.gov Identifier:	NCT01092572 History of Changes
Other Study ID Numbers:	CF-Man-Statin-1
Study First Received:	March 23, 2010
Last Updated:	January 29, 2014
Health Authority:	Canada: Health Canada

Keywords provided by University of British Columbia:


cystic fibrosis adult cystic fibrosis

Additional relevant MeSH terms:


Fibrosis Inflammation Cystic Fibrosis Pathologic Processes Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn	Infant, Newborn, Diseases Simvastatin Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016

Statins To Treat Adult Cystic Fibrosis (CFStatin)