Effect of Simvastatin on CF Airway Inflammation

NCT00255242 | Completed Phase 1

• 1 other identifier: KRAYNA04A0
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Individuals with cystic fibrosis (CF) have persistent infection in the airways, which the body attempts to fight by recruiting immune cells (neutrophils) to the lung. The immune system and neutrophils are unable to completely kill the bacteria, and the response to the infection leads to inflammation (swelling) of the airways and lung damage. Nitric oxide (NO) has anti-bacterial and anti-inflammatory properties in the lung. NO production is decreased in CF patients, and may contribute to the persistent infection and inflammation. Increasing the production of NO in the airways of CF patients may help decrease this inflammation and infection. Rho GTPases are molecules in the cells that line the airways that decrease the protein that makes nitric oxide (NOS). Rho proteins also increase inflammation in these cells. Rho proteins are increased in CF cells, and may partially explain the low NO and high inflammation seen in CF. Blocking the Rho protein in CF cells increases NOS, which can then produce more NO. The Rho protein can be inhibited with a drug, simvastatin (Zocor®). Simvastatin is used by millions of people to lower their cholesterol, is very safe, has few side-effects and is approved for use in children greater than 10 years of age. We propose that treating CF patients with simvastatin will increase NO produced (exhaled NO), and may decrease airway inflammation. If simvastatin has these expected effects in CF, it would be another drug that has potential to become a new therapy to fight the debilitating lung damage of the disease.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Airway Inflammation; Cytokines; Simvastatin; HMG-CoA reductase inhibitors; Rho GTP-ase

Outcome Measures

Primary Outcomes (1)

• Specific Aim 1: To determine the effect of simvastatin treatment on exhaled NO, eNO measurements from the Run-in phase will be compared to the Treatment phase.

  1 month

Secondary Outcomes (2)

• Specific Aim 2: Synthesis of the following markers will be measured in nasal epithelial samples by quantitative PCR.

  1 months

• Specific Aim 3: Cell and differential counts will be obtained in induced sputum as an overall measure of the inflammatory response.Concentrations of neutrophil products (elastase) and cytokines also will be measured in induced sputum.

  1 months

Interventions

Simvastatin treatment for 28 days DRUG

40 mg / day

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Cystic Fibrosis
• \> 9 yrs of age
• Clinically stable
• FEV1 \> 50% predicted

You may not qualify if:

• Hepatic disease
• B. cepacia
• corticosteroids
• symptomatic allergic rhinitis

Sponsors & Collaborators

• Akron Children's Hospital: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (1)

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Nathan C Kraynack, MD

  Akron Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 16, 2005
• First Posted: November 18, 2005
• Study Start: July 1, 2004
• Primary Completion: March 1, 2008
• Study Completion: May 1, 2009
• Last Updated: August 3, 2009

Record last verified: 2008-01

Locations

US (1)