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

Chronic Obstructive Pulmonary Disease Clinical Trial

— CASCADE  

Official title:

Depression and Functional Outcomes in COPD: Impact of Genetics and Inflammation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01074515
• Other study ID #: 37332-B
• Secondary ID: R01HL093146-01A2
• Status: Active, not recruiting
• Phase: N/A
• First received: February 11, 2010
• Last updated: December 1, 2015
• Start date: February 2010
• Est. completion date: February 2016

Study information

• Verified date: December 2015
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 350
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Locations

Country	Name	City	State
United States	South Texas Veterans Health Care System	San Antonio	Texas
United States	The University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Puget Sound Veterans Administration Health Care System	Seattle	Washington
United States	University of Washington	Seattle	Washington

Sponsors (5)

Lead Sponsor	Collaborator
University of Washington	National Heart, Lung, and Blood Institute (NHLBI), South Texas Veterans Health Care System, The University of Texas Health Science Center at San Antonio, VA Puget Sound Health Care System

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Depression		1 year & 2 year	No
Secondary	Physical activity by accelerometry		1 year & 2 year	No
Secondary	Dyspnea		1 year & 2 year	No
Secondary	Health related quality of life		1 year & 2 year	No
Secondary	Six Minute Walk Distance		1 year & 2 year	No

External Links

•   CASCADE Study Web Site