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

Sponsor

University of Washington (Other)

Overall Status

Unknown status

CT.gov ID

NCT01074515

Collaborator

VA Puget Sound Health Care System (U.S. Fed), The University of Texas Health Science Center at San Antonio (Other), South Texas Veterans Health Care System (U.S. Fed), National Heart, Lung, and Blood Institute (NHLBI) (NIH)

350

Enrollment

Locations

Duration (Months)

87.5

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

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	Intervention/Treatment	Phase
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.

Study Design

Study Type:

Observational

Anticipated 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 :

Feb 1, 2010

Anticipated Primary Completion Date :

Feb 1, 2016

Anticipated Study Completion Date :

Feb 1, 2016

Outcome Measures

Primary Outcome Measures

Depression [1 year & 2 year]

Secondary Outcome Measures

Physical activity by accelerometry [1 year & 2 year]
Dyspnea [1 year & 2 year]
Health related quality of life [1 year & 2 year]
Six Minute Walk Distance [1 year & 2 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	South Texas Veterans Health Care System	San Antonio	Texas	United States	78229
2	The University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
3	Puget Sound Veterans Administration Health Care System	Seattle	Washington	United States	98108
4	University of Washington	Seattle	Washington	United States	98195