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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
VA Puget Sound Health Care System
The University of Texas Health Science Center at San Antonio
South Texas Veterans Health Care System
Information provided by (Responsible Party):
Huong Nguyen, University of Washington
ClinicalTrials.gov Identifier:
NCT01074515
First received: February 11, 2010
Last updated: September 6, 2013
Last verified: September 2013
  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

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Depression [ Time Frame: 1 year & 2 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Pulmonary and primary care clinics and community sample

Criteria

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
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: NCT01074515

Locations
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
Investigators
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 by University of Washington

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Huong Nguyen, Study Principal investigator, 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: September 6, 2013
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
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Behavioral Symptoms
Mental Disorders
Mood Disorders
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 29, 2014