Safety of Anti-Depressant for Chronic Obstructive Pulmonary Disease (SAD-COPD)

Study Overview
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Brief Summary
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Objective: Determine whether treatment of perceived stress, anxiety, and depression with anti-depressant therapy improves dyspnea scores, 6-minute walk (6MW) distance and quality of life (QoL) in patients with Chronic Obstructive Pulmonary Disease (COPD) and ILD (Interstitial Lung Disease) undergoing pulmonary rehab. The study is a prospective, randomized, double-blinded, placebo-controlled study to assess the effect of an SSRI on 6MW, dyspnea scores, and QoL in COPD and ILD patients undergoing pulmonary rehab. Thirty subjects that carry an ICD-9 code diagnosis of COPD and/or ILD and CES-D (Center for Epidemiologic Studies Depression) score of > 16 will be recruited from Duke Pulmonary Rehab. Multivariable regression models will be constructed to evaluate the relationship between perceived stress, anxiety, and depression with adjustments by race, gender, age, BMI and GOLD score. A multivariable regression model will be constructed to assess whether treatment of perceived stress, depression, and anxiety with antidepressant therapy (sertraline) is an effect modifier on 6MW distance and dyspnea scores in patients with COPD or ILD who are enrolled in pulmonary rehab. Descriptive statistics will be used to examine the socio-demographic characteristic data. Student t-tests will be performed to assess group differences in continuous data. Categorical variables will be examined using the Pearson's Chi-Squared test.

Official Title
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Safety of Anti-Depressant for Chronic Obstructive Pulmonary Disease

Conditions
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Anxiety, COPD, Depression, Stress, Interstitial Lung Disease

Intervention / Treatment
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* Drug: Sertraline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female with an ICD-9 code diagnosis of COPD and/or ILD Mild, moderate, or severe major depression symptoms based on Center of Epidemiologic Studies Depression (CES-D) score > 16. Able to complete informed consent† Read and write in English Exclusion Criteria: Current treatment with antidepressants Current treatment with anti-psychotics Severe physical disability that would interfere with lung assessment History of major psychiatric illness, including bipolar disorder, psychoses, and/or severe personality disorder. Active suicidal ideations Serious cognitive problems (dementia syndrome) or cognitive impairment defined as MMSE < 22 Recent loss of spouse within 6 weeks of study enrollment. History of alcohol or drug dependence in the last 6 months. Pregnant women or nursing mothers Poorly controlled concomitant conditions that pose additional procedure risk as determined by the investigator.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pulmonary Rehab + Study Drug<br>Subjects randomized into this arm will be given active study drug (sertraline). Subjects will take 25mg tablets by mouth daily starting at visit 1 along with participating in the intensive pulmonary rehab program. Subjects will be assessed at one week intervals +/- 7 days for tolerability and side effects, and if tolerating study drug, the dose will be increased weekly by 25mg over the course of the first four weeks with maximum effective dose of 100mg daily by the end of week four. Subjects will continue this dose over the course of the remaining 8 weeks of the study, while participating in the graduate program of pulmonary rehab. | Drug: Sertraline<br> <br> |
| Placebo Comparator: Pulmonary Rehab + Placebo<br>Subjects randomized to the placebo arm will have the same procedures as described above in the study drug arm with the exception that they will be receiving matched placebo drug. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 6MW distance | Patients will undergo 6-minute walk at visit 1(baseline), visit 4 (after one month of study drug + intensive pulmonary rehab), and visit 6 (week 12). | visit 1(baseline), visit 4 (after one month of study drug + intensive pulmonary rehab), and visit 6 (week 12). | 
| Change in dyspnea scores, as measured by UCSD Medical Center Pulmonary Rehabilitation Program Shortness of Breath Questionnaire (UCSD-SOB) | To monitor changes in dyspnea scores, patients will complete the UCSD Medical Center Pulmonary Rehabilitation Program Shortness of Breath Questionnaire (UCSD-SOB). Patients will complete this at all visits (1-6). | visit 1(baseline), visit 2 (week 2), visit 3 (week 3), visit 4 (week 4), visit 5 (week 8), visit 6 (week 12) | 
| Change in quality of life, as measured by Ferrans & Powers Quality of Life Index - Pulmonary version (QOL) | To monitor changes in quality of life, patients will complete the Ferrans & Powers Quality of Life Index - Pulmonary version (QOL). Patients will complete this at all visits (1-6). | visit 1(baseline), visit 2 (week 2), visit 3 (week 3), visit 4 (week 4), visit 5 (week 8), visit 6 (week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in perceived stress, as measured by General Health Questionnaire-12 (GHQ-12) | To monitor changes in perceived stress, patients will complete the General Health Questionnaire-12 (GHQ-12). | visit 1 (baseline), visit 2 (week 2), visit 3 (week 3), visit 4 (week 4), visit 5 (week 8), visit 6 (week 12) | 
| Change in anxiety, as measured by Hamilton Anxiety and Depression Scale (HADS) |  | visit 1(baseline), visit 2 (week 2), visit 3 (week 3), visit 4 (week 4), visit 5 (week 8), visit 6 (week 12) | 
| Change in anxiety, as measured by Anxiety Inventory for Respiratory Disease (AIR) |  | visit 1(baseline), visit 2 (week 2), visit 3 (week 3), visit 4 (week 4), visit 5 (week 8), visit 6 (week 12) | 
| Change in depression, as measured by Hamilton Anxiety and Depression Scale (HADS) |  | visit 1 (baseline), visit 2 (week 2), visit 3 (week 3), visit 4 (week 4), visit 5 (week 8), visit 6 (week 12) | 
| Tolerability as measured by evidence of serotonin syndrome, significant agitation or tremor, worsening in anxiety or depression such that the subject is having suicidal ideation or intent | Intolerability will be defined as evidence of serotonin syndrome, significant agitation or tremor, worsening in anxiety or depression such that the subject is having suicidal ideation or intent. | visit 2 (week 2), visit 3 (week 3), visit 4 (week 4) |