Chronic Obstructive Pulmonary DiseaseCASCADENCT01074515
Chronic Obstructive Pulmonary Disease (COPD) Activity: Serotonin Transporter (SERT), Cytokines and Depression (CASCADE Study)
An observational study of Chronic Obstructive Pulmonary Disease, run by University of Washington at 4 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- How many people
- 350 participants
- Where
- 4 sitesUnited States
- Study dates
- Feb 2010to Feb 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Pulmonary and primary care clinics and community sample
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
South Texas Veterans Health Care System
San Antonio, Texas, 78229
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Puget Sound Veterans Administration Health Care System
Seattle, Washington, 98108
University of Washington
Seattle, Washington, 98195
About this study
Official title: Depression and Functional Outcomes in COPD: Impact of Genetics and Inflammation
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.
Read the 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.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- COPD, Depression, Inflammation, Genetics, Functioning, Dyspnea, Physical activity
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Depression, Inflammation, Dyspnea, Motor Activity
What is being measured
The primary outcome is the main question the study is designed to answer.
Depression
Measured: 1 year & 2 year
Secondary outcomes (4)
Physical activity by accelerometry
Measured: 1 year & 2 year
Dyspnea
Measured: 1 year & 2 year
Health related quality of life
Measured: 1 year & 2 year
Six Minute Walk Distance
Measured: 1 year & 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2010 (estimated)
- Study startFeb 2010
- Primary completionFeb 2016 (estimated)
- Study completionFeb 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- 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)
- Responsible party
- Principal investigator, Huong Nguyen, University of Washington
- Investigators
- Huong Q Nguyen, PhD, RN, Principal investigator, University of WashingtonVincent Fan, MD, MPH, Principal investigator, Puget Sound Veteran's Affair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01074515
- Sponsor's protocol ID
- 37332-B
- Other IDs
- R01HL093146-01A2
- Acronym
- CASCADE
- Status last verified
- Dec 2015
- First submitted
- 11 Feb 2010
- Last updated
- 3 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Chen Z, Fan VS, Belza B, Pike K, Nguyen HQ. Association between Social Support and Self-Care Behaviors in Adults with Chronic Obstructive Pulmonary Disease. Ann Am Thorac Soc. 2017 Sep;14(9):1419-1427. doi: 10.1513/AnnalsATS.201701-026OC.
PubMed 28719225Nguyen HQ, Herting JR, Pike KC, Gharib SA, Matute-Bello G, Borson S, Kohen R, Adams SG, Fan VS. Symptom profiles and inflammatory markers in moderate to severe COPD. BMC Pulm Med. 2016 Dec 3;16(1):173. doi: 10.1186/s12890-016-0330-1.
PubMed 27914470Nguyen HQ, Fan VS, Herting J, Lee J, Fu M, Chen Z, Borson S, Kohen R, Matute-Bello G, Pagalilauan G, Adams SG. Patients with COPD with higher levels of anxiety are more physically active. Chest. 2013 Jul;144(1):145-151. doi: 10.1378/chest.12-1873.
PubMed 23370503
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Depression and Functional Outcomes in COPD: Impact of Genetics and Inflammation
- ClinicalTrials.gov ID
- NCT01074515
- Acronym / sponsor ID
- CASCADE / 37332-B
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- COPD, Depression, Inflammation, Genetics, Functioning, Dyspnea, Physical activity
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- 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)
- Study start
- Feb 2010
- Primary completion
- Feb 2016 (estimated)
- Study completion
- Feb 2016 (estimated)
- First posted
- 24 Feb 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Pulmonary and primary care clinics and community sample
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Depression
Time frame: 1 year & 2 year
4 secondary outcomes
Physical activity by accelerometry
Time frame: 1 year & 2 year
Dyspnea
Time frame: 1 year & 2 year
Health related quality of life
Time frame: 1 year & 2 year
Six Minute Walk Distance
Time frame: 1 year & 2 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2015.
- Derived from this study: PubMed 28719225Chen Z, Fan VS, Belza B, Pike K, Nguyen HQ. Association between Social Support and Self-Care Behaviors in Adults with Chronic Obstructive Pulmonary Disease. Ann Am Thorac Soc. 2017 Sep;14(9):1419-1427. doi: 10.1513/AnnalsATS.201701-026OC.
- Derived from this study: PubMed 27914470Nguyen HQ, Herting JR, Pike KC, Gharib SA, Matute-Bello G, Borson S, Kohen R, Adams SG, Fan VS. Symptom profiles and inflammatory markers in moderate to severe COPD. BMC Pulm Med. 2016 Dec 3;16(1):173. doi: 10.1186/s12890-016-0330-1.
- Derived from this study: PubMed 23370503Nguyen HQ, Fan VS, Herting J, Lee J, Fu M, Chen Z, Borson S, Kohen R, Matute-Bello G, Pagalilauan G, Adams SG. Patients with COPD with higher levels of anxiety are more physically active. Chest. 2013 Jul;144(1):145-151. doi: 10.1378/chest.12-1873.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Huong Q Nguyen, PhD, RN principal investigator
University of Washington
Vincent Fan, MD, MPH principal investigator
Puget Sound Veteran's Affair
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Obstructive Pulmonary Disease, run by University of Washington at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Depression (time frame: 1 year & 2 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01074515, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2015.