T Lymphocyte Cells in Individuals Experiencing an Acute Exacerbation of Chronic Obstructive Pulmonary Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by University of Michigan
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jeffrey L. Curtis, University of Michigan
ClinicalTrials.gov Identifier:
NCT00281229
First received: January 20, 2006
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to determine whether the lungs of individuals with chronic obstructive pulmonary disease (COPD) contain resident memory T lymphocytes that can produce a combination of cytokines that induce the symptoms of an acute exacerbation of COPD (AE-COPD). Specifically, the study will determine cell-surface receptors of lung T cells in comparison with blood T cells from the same subject, and will examine anti-CD3-activated blood or lung T cells for interleukin (IL)-6 and interferon-gamma production in response to IL-18, and for IL-17A production in response to recombinant IL-23.


Condition
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Innate and Adaptive Immunity in COPD Exacerbations: Surgical Volunteers

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • phenotype and in vitro functions of lung lymphocytes [ Time Frame: within 3 days of surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: September 2005
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Detailed Description:

BACKGROUND:

COPD is one of the most pressing healthcare problems facing our nation. AE-COPD is responsible for the bulk of healthcare costs, and much of the morbidity and decline in health status among individuals with this common disease. The lack of accepted animal models of AE-COPD necessitates novel approaches using human samples. Advances in the understanding of the pathogenesis have been slowed, in part, due to controversy as to how exacerbations should be defined. The prevailing paradigm has defined AE-COPD as event-based. Such definitions clearly identify groups of patients with accelerated loss of pulmonary function and increased mortality. However, limited data show that symptom-based definitions of AE-COPD also capture episodes inducing significant morbidity and functional decline, and hence of concern to patients. Fundamental mechanisms are lacking to explain AE-COPD defined by either means.

Controversy also surrounds triggers of AE-COPD. Bacteria and viruses are involved in some episodes, but the relative importance of each is intertwined with disputes over the definition of AE-COPD. Progress at linking specific pathogens to molecular pathogenesis has been slow, both due to their diversity, and to the high rates of bacterial colonization of patients with COPD, even in the stable state. Moreover, in many AE-COPD cases, no pathogen can be identified. Without negating the value of analyzing infections with specific species of pathogens, it appears that progress in molecular pathogenesis could be accelerated by focusing on unifying features of the pulmonary immune response during AE-COPD.

DESIGN NARRATIVE:

The research protocol involves isolating lung lymphocytes from surgical specimens of patients already undergoing clinically indicated lung resections. Surgical lung resections may be performed either by open thoracotomy or by video-assisted thoracoscopic surgery (VATS), and could include pneumonectomies, lobectomies, or wedge-excisions, as dictated by clinical care of the patient. This protocol will exclusively use tissue that is of excess after a clinical diagnosis is established. The setting is the operating rooms at the Ann Arbor VA Hospital or the University of Michigan Hospital System. Subjects will be recruited from the outpatient clinics, but will be inpatients at the time of surgery.

Subjects will not undergo any additional procedures beyond routine clinical care as a result of participating in this protocol. However, it is anticipated that the study will have access to the medical record to extract results of demographic data, including occupational exposures and smoking history, pulmonary function testing, and results of imaging and other staging studies.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Subjects undergoing clinically indicated lung resections.

Criteria

Inclusion criteria:

  • Diagnosis of COPD AND underwent lung resection for malignancy OR lung volume reduction surgery OR lung transplantation OR lung resection for nodules and masses

Exclusion criteria:

  • Mental incompetence or active psychiatric illness
  • Currently using more than 20 mg/day of Prednisone
  • Asthma as primary clinical pulmonary diagnosis
  • Cystic fibrosis
  • Clinically significant bronchiectasis
  • Other inflammatory or fibrotic lung disease
  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: NCT00281229

Contacts
Contact: Jeffrey L. Curtis, M.D. 734-845-3457 jlcurtis@umich.edu
Contact: Lisa McCloskey, RRT 734-769-7100 ext 5-6180 lmcclosk@umich.edu

Locations
United States, Michigan
University of Michigan at Ann Arbor Recruiting
Ann Arbor, Michigan, United States, 48105
Contact: Catherine Meldrum, B.S, R.N.    734-764-7388    cgetty@med.umich.edu   
Contact: Lisa McCloskey, RRT    734-769-7100 ext 5-3533    lmcclosk@umich.edu   
Principal Investigator: Jeffrey L. L Curtis, M.D.         
Sub-Investigator: Fernando J Martinez, M.D., M.S.         
Sub-Investigator: MeiLan K Han, M.D., M.S.         
VA Ann Arbor Healthcare System Recruiting
Ann Arbor, Michigan, United States, 48105
Contact: Lisa McCloskey, RRT    734-769-7100 ext 5-6180    lmcclosk@umich.edu   
Principal Investigator: Jeffrey L. Curtis, M.D.         
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: Jeffrey L. Curtis, M.D University of Michigan at Ann Arbor
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jeffrey L. Curtis, Professor of Internal Medicine, University of Michigan
ClinicalTrials.gov Identifier: NCT00281229     History of Changes
Other Study ID Numbers: 1328, R01HL082480, R01 HL82480
Study First Received: January 20, 2006
Last Updated: July 15, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Michigan:
Chronic Obstructive Pulmonary Disease
COPD

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on August 27, 2014