Cystic Fibrosis (CF) Leukocyte Genes as Biomarkers for Novel Therapies

NCT00727285 | Completed DMC

• 1 other identifier: NICK07A0
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Presently, effectiveness of treatments for CF lung disease is judged by improvement in lung function (FEV1). However, in CF patients, FEV1 can range from severely decreased to normal, and improvements may occur slowly. Thus, clinical trials require many patients over prolonged periods to evaluate medications. As the pace of drug development accelerates, it is no longer possible to test all of the promising candidate therapies using conventional study designs. A sensitive technique for assessing lung inflammation has been developed which uses the expression of genes located in circulating blood cells. Mononuclear cells pass repeatedly through the blood vessels of the lung, and are exposed to many of the inflammatory products that are present in the airways. Over the past 4 years the investigators have identified a small group of candidate genes that are unregulated or downregulated in response to antibiotic treatment. The investigators now propose to prospectively test this method of quantifying lung inflammation in a large group of CF patients undergoing treatment of pulmonary exacerbations. Blood will be sampled before and after antibiotic treatment for a pulmonary exacerbation, and the relative change in gene expression will be compared to improvement in FEV1 and other clinical responses, to determine the utility of this method for use in studies. If successful, this technique could allow for a rapid and noninvasive method to gauge immediate effects by new treatments, and assist caregivers in determining optimal treatment strategies for the individual.

Conditions

Cystic Fibrosis; Pulmonary Exacerbation

Keywords

Cystic Fibrosis; pulmonary exacerbation; gene expression; biomarker; inflammation; CF pulmonary exacerbation

Outcome Measures

Primary Outcomes (1)

• The Primary analysis is the change in expression of individual and combinations of mononuclear cell genes, obtained pre- and post-antibiotic therapy.

  14-21 days

Secondary Outcomes (2)

• Correlation of changes in PBMC gene expression with changes in FEV1

  14-21 days

• Correlation of changes in PBMC gene expression with changes in WBC counts.

  14-21 days

Study Arms (1)

A

CF patients followed by the Adult CF Program at National Jewish Health meeting criteria for an acute pulmonary exacerbation.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

CF patients followed by the Adult CF Program at National Jewish Health, who are ≥ 18 years and present with signs and symptoms of an acute pulmonary exacerbation. All subjects will be treated with at least two pathogen specific I.V. antibiotics for a minimum of 10 days, along with standard guidelines for other aspects of care for an acute pulmonary exacerbation. Concomitant use of inhaled antibiotics and systemic steroids will be allowed, and typical co-infections or co-morbidities will not result in exclusion.

You may qualify if:

• Documented diagnosis of CF.
• Age 18 years old or greater.
• Presentation at the start of treatment for a pulmonary exacerbation of CF.
• Ability to perform reproducible Pulmonary Function Tests.
• Willingness to comply with study procedure and willingness to provide written consent.

You may not qualify if:

• Participation in an investigational drug study within one month of enrollment.
• Presence of a condition or abnormality that, in the opinion of the Principal Investigator (PI), would compromise the safety of the patient or the quality of the data.

Sponsors & Collaborators

• National Jewish Health: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (1)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Related Publications (1)

• Nick JA, Sanders LA, Ickes B, Briones NJ, Caceres SM, Malcolm KC, Brayshaw SJ, Chacon CS, Barboa CM, Jones MC, St Clair C, Taylor-Cousar JL, Nichols DP, Sagel SD, Strand M, Saavedra MT. Blood mRNA biomarkers for detection of treatment response in acute pulmonary exacerbations of cystic fibrosis. Thorax. 2013 Oct;68(10):929-37. doi: 10.1136/thoraxjnl-2012-202278. Epub 2013 Jun 19.

  PMID: 23783371 RESULT

MeSH Terms

Conditions

Cystic Fibrosis; Inflammation

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jerry A Nick, M.D.

  National Jewish Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2008
• First Posted: August 1, 2008
• Study Start: February 1, 2008
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2012
• Last Updated: March 29, 2017

Record last verified: 2017-03

Locations

US (1)