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Chronic Obstructive Pulmonary Disease (COPD) Activity: Serotonin Transporter (SERT), Cytokines and Depression (CASCADE Study) (CASCADE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01074515
Recruitment Status : Unknown
Verified December 2015 by Huong Nguyen, University of Washington.
Recruitment status was:  Active, not recruiting
First Posted : February 24, 2010
Last Update Posted : December 3, 2015
VA Puget Sound Health Care System
The University of Texas Health Science Center at San Antonio
South Texas Veterans Health Care System
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Huong Nguyen, University of Washington

Brief Summary:
The goal of the study is to look at how genes and certain chemicals in the body are related to depression and chronic obstructive pulmonary disease.

Condition or disease
Chronic Obstructive Pulmonary Disease

Detailed Description:
Depression is highly prevalent among patients with chronic obstructive pulmonary disease (COPD) and is associated with adverse clinical outcomes. The overall goal of this proposal is to examine the impact of inflammation and genetic risk factors on depression in patients with severe COPD, and to assess the combined effects of inflammation, genetics, and depression on changes in functional outcomes. There is increasing evidence that COPD is associated with systemic inflammation that impacts other organ systems. High levels of systemic inflammatory markers have also been linked to increased risk of depression in both healthy and chronically ill populations. The neurotransmitter serotonin which is involved in the pathophysiology of affective disorders is regulated by the serotonin transporter (SERT) that controls reuptake of serotonin at brain synapses. Recent studies report that SERT polymorphisms are associated with depression, suggesting that variants of this gene may be important in determining whether patients with COPD will develop depression during the course of their disease. The preliminary data linking SERT polymorphisms with depression and data suggesting a relationship between inflammation, depression and COPD strongly argue for a large scale prospective study to critically test these relationships. Therefore, the aims of this prospective study of patients with moderate to very severe COPD are to: 1) Examine the relationship between SERT polymorphisms with depression; 2) Examine the bi-directional longitudinal relationship between markers of systemic inflammation (CRP, IL-1ra, IL-6, IL-12, TNF-α, and IFN-γ) and depressive symptoms in COPD, and explore the role of exacerbations and SERT genotype in this relationship; and 3) Determine the relationship of depression, inflammation, and SERT genotype with decline in functional outcomes (six minute walk test distance, physical activity measured with accelerometers, dyspnea severity, and health related quality of life) in COPD over 2 years. Patients with COPD GOLD Stages II-IV (n=350) will be recruited from two clinical sites over 30 months. Assessments at baseline, year 1 and year 2 will include: blood samples for genotyping (5-HTTLPR, STin2 VNTR, and rs25331) and cytokine assays (CRP, IL-1ra, IL-6, IL-12, TNF-α, and IFN-γ), spirometry, assessment of depression, functional capacity (six minute walk test), performance (physical activity derived from accelerometry), dyspnea, and health related quality of life (HRQL). We will use advanced longitudinal statistical techniques, structural equations modeling and latent growth models, to assess the dynamics of change in depression, inflammation, and functional status as posited by our models as these processes unfold over time.

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Study Type : Observational
Estimated Enrollment : 350 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Depression and Functional Outcomes in COPD: Impact of Genetics and Inflammation
Study Start Date : February 2010
Estimated Primary Completion Date : February 2016
Estimated Study Completion Date : February 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: COPD Lung Diseases

Primary Outcome Measures :
  1. Depression [ Time Frame: 1 year & 2 year ]

Secondary Outcome Measures :
  1. Physical activity by accelerometry [ Time Frame: 1 year & 2 year ]
  2. Dyspnea [ Time Frame: 1 year & 2 year ]
  3. Health related quality of life [ Time Frame: 1 year & 2 year ]
  4. Six Minute Walk Distance [ Time Frame: 1 year & 2 year ]

Biospecimen Retention:   Samples With DNA
Whole blood

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Pulmonary and primary care clinics and community sample

Inclusion Criteria:

  • Diagnosis of COPD confirmed by the following: 1) FEV1/FVC < 70%; 2) Moderate to very severe disease by GOLD criteria (FEV1 <65%); 2) Age > 40 years; and 3) A significant history of current or past cigarette smoking (> 10 pack-years);
  • Stable disease with no acute exacerbations of COPD in the past 4 weeks;
  • Ability to speak, read and write English

Exclusion Criteria:

  • Acute COPD exacerbation within the past 4 weeks (temp exclusion)
  • Chronic obstructive lung disorders unrelated to COPD: asthma, bronchiectasis, cystic fibrosis
  • Idiopathic Pulmonary Fibrosis
  • Congestive Heart Failure
  • Chronic renal failure requiring dialysis
  • Primary pulmonary vascular disease
  • Chronic inflammatory, infectious or auto-immune disease, e.g. osteomyelitis, crohn's disease or rheumatoid arthritis
  • Chronic liver disease
  • Metastatic cancer
  • Chronic antibiotic use or ongoing infection
  • Chronic oral prednisone use
  • Moderate to severe dementia
  • Severe primary mental illness, e.g. schizophrenia, bipolar disease, severe obsessive compulsive disorder
  • <2 years life expectancy
  • History of fainting with spirometry

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01074515

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United States, Texas
South Texas Veterans Health Care System
San Antonio, Texas, United States, 78229
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
United States, Washington
Puget Sound Veterans Administration Health Care System
Seattle, Washington, United States, 98108
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Washington
VA Puget Sound Health Care System
The University of Texas Health Science Center at San Antonio
South Texas Veterans Health Care System
National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: Huong Q Nguyen, PhD, RN University of Washington
Principal Investigator: Vincent Fan, MD, MPH Puget Sound Veteran's Affair
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Huong Nguyen, Study Principal investigator, University of Washington Identifier: NCT01074515    
Other Study ID Numbers: 37332-B
R01HL093146-01A2 ( U.S. NIH Grant/Contract )
First Posted: February 24, 2010    Key Record Dates
Last Update Posted: December 3, 2015
Last Verified: December 2015
Keywords provided by Huong Nguyen, University of Washington:
Physical activity
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Behavioral Symptoms
Respiratory Tract Diseases