Chronic Obstructive Pulmonary Disease (COPD) Activity: Serotonin Transporter (SERT), Cytokines and Depression (CASCADE Study)
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Purpose
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 |
|---|
|
Chronic Obstructive Pulmonary Disease |
| Study Type: | Observational |
| Study Design: | Observational Model: Cohort Time Perspective: Prospective |
| Official Title: | Depression and Functional Outcomes in COPD: Impact of Genetics and Inflammation |
- Depression [ Time Frame: 1 year & 2 year ] [ Designated as safety issue: No ]
- Physical activity by accelerometry [ Time Frame: 1 year & 2 year ] [ Designated as safety issue: No ]
- Dyspnea [ Time Frame: 1 year & 2 year ] [ Designated as safety issue: No ]
- Health related quality of life [ Time Frame: 1 year & 2 year ] [ Designated as safety issue: No ]
- Six Minute Walk Distance [ Time Frame: 1 year & 2 year ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
Whole blood
| Estimated Enrollment: | 350 |
| Study Start Date: | February 2010 |
| Estimated Study Completion Date: | January 2015 |
| Estimated Primary Completion Date: | October 2014 (Final data collection date for primary outcome measure) |
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.
Eligibility| Ages Eligible for Study: | 40 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
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
Contacts and Locations| Contact: Huong Nguyen, PhD, RN | 206-543-8651 | hqn@uw.edu |
| United States, Texas | |
| The University of Texas Health Science Center at San Antonio | Not yet recruiting |
| San Antonio, Texas, United States, 78229 | |
| Contact: Timothy Houlihan, RN 210-617-5300 ext 14549 houlihan@uthscsa.edu | |
| Principal Investigator: Sandra Adams, MD | |
| South Texas Veterans Health Care System | Not yet recruiting |
| San Antonio, Texas, United States, 78229 | |
| Contact: Timothy Houlihan, RN 210-617-5300 ext 14549 houlihan@uthscsa.edu | |
| Principal Investigator: Sandra Adams, MD | |
| United States, Washington | |
| Puget Sound Veterans Administration Health Care System | Not yet recruiting |
| Seattle, Washington, United States, 98108 | |
| Contact: Vincent Fan, MD, MPH | |
| Principal Investigator: Vincent Fan, MD, MPH | |
| University of Washington | Recruiting |
| Seattle, Washington, United States, 98195 | |
| Contact: Cynthia Lotane, BA 206-685-4094 cascade1@uw.edu | |
| Sub-Investigator: Soo Borson, MD | |
| Sub-Investigator: Ruth Kohen, MD | |
| Sub-Investigator: Gustave Matute-Bello, MD | |
| Sub-Investigator: Jerald Herting, PhD | |
| Principal Investigator: Vincent Fan, MD, MPH | |
| Principal Investigator: | Huong Q Nguyen, PhD, RN | University of Washington |
| Principal Investigator: | Vincent Fan, MD, MPH | Puget Sound Veteran's Affair |
More Information
Additional Information:
No publications provided
| Responsible Party: | University of Washington |
| ClinicalTrials.gov Identifier: | NCT01074515 History of Changes |
| Other Study ID Numbers: | 37332-B, R01HL093146-01A2 |
| Study First Received: | February 11, 2010 |
| Last Updated: | October 15, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by University of Washington:
|
COPD Depression Inflammation Genetics |
Functioning Dyspnea Physical activity |
Additional relevant MeSH terms:
|
Depression Depressive Disorder Inflammation Lung Diseases Respiration Disorders Pulmonary Disease, Chronic Obstructive |
Lung Diseases, Obstructive Behavioral Symptoms Mood Disorders Mental Disorders Pathologic Processes Respiratory Tract Diseases |
ClinicalTrials.gov processed this record on May 16, 2013