BRAIN, Symptoms, and Physical Activity in COPD

Study Overview
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Brief Summary
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Persons with COPD have both chronic musculoskeletal pain and dyspnea that require accurate diagnosis and treatment, ultimately to optimize functional status. The investigators propose to use advanced neuroimaging techniques to understand central mechanisms of chronic pain, dyspnea, and physical activity promotion in COPD. The investigators' novel proposal to correlate subjective symptoms (chronic pain and dyspnea) with an objective central biomarker (resting state functional connectivity) and examine their changes in response to a non-pharmacological, non-addictive physical activity intervention will personalize the care of Veterans with COPD.

Detailed Description
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COPD is the nation's third leading cause of death and affects up to 11% of all VA healthcare patients. Patients with COPD experience significant dyspnea despite optimization of medical therapy. In addition, over half of patients with COPD experience chronic pain--largely musculoskeletal pain. Clinically, in patients who suffer from both chronic pain and dyspnea, it is difficult to distinguish a patient's perception of one symptom modulated by the other. Novel objective diagnostic tools are needed to complement patient self-report and accurately distinguish symptoms in patients who have both chronic pain and dyspnea to optimize clinical management. It is also important to study chronic pain and dyspnea in COPD because they are common barriers to engaging in physical activity (PA) and exercise. The clinical course of COPD is characterized by a downward spiral of dyspnea and chronic pain, physical inactivity, and significant functional limitation. Although chronic pain and dyspnea can be barriers, PA and exercise are powerful, but underused, non-addictive therapies for management of these symptoms in COPD. The investigators developed Every Step Counts (ESC), a technology-mediated intervention based on the Theory of Self-Regulation, to promote PA in COPD. The investigators have demonstrated ESC's safety, feasibility, and efficacy to increase PA and improve health-related quality of life in Veterans with COPD. In two separate studies using questionnaires, ESC has been shown to improve dyspnea in COPD and relieve chronic back pain in Veterans. An important next step is to understand the mechanisms of benefit of PA interventions, like ESC, in the many COPD patients with both chronic musculoskeletal pain and dyspnea to ultimately design better PA interventions and optimize treatment of these symptoms. Currently, the central mechanisms of chronic pain and dyspnea, and how they change in response to PA promotion in COPD are largely unknown. It has been shown that pre-stimulus resting state functional connectivity determines pain perception in healthy humans. Resting state fcMRI evaluates interactions between brain regions before a sensory event or when an explicit task is not being performed. These communications are altered in older adults with chronic musculoskeletal pain. Functional connectivity among regions specifically within the default mode network (DMN) (posterior cingulate, inferior parietal lobes, and medial frontal gyrus) have been examined in clinical disease states, as this network is reliably detected and well-characterized. Functional connectivity may be a novel biomarker of chronic pain and dyspnea. Aim 1: Characterize and correlate the relationship between functional connectivity and chronic musculoskeletal pain and dyspnea in 30 persons with COPD (10 with both symptoms, 10 with chronic pain, and 10 with dyspnea). Aim 2: Explore changes in functional connectivity and changes in symptoms in 30 persons with COPD after use of the ESC intervention to increase PA. The investigators' proposed design will leverage enrollment of well-characterized participants with COPD already using the ESC PA intervention as part of a distinct and ongoing RR&D Merit Award. This proposal will provide insight into the biologically complex relationships between symptoms (chronic pain and dyspnea), behavior (PA), and biology at the central level (functional connectivity).

Official Title
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Effects of Chronic Pain, Dyspnea, and Physical Activity Promotion on Functional Connectivity of the Brain in COPD

Conditions
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COPD, Chronic Musculoskeletal Pain

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Greater than or equal to 40 years of age Clinical diagnosis of COPD defined as either a ratio of FEV1 to forced vital capacity < 0.70 or chest CT evidence of emphysema or prior documentation of FEV1/FVC ratio of < 0.7 and clinical evidence of COPD (defined as 10 pack-year cigarette smoking history, dyspnea, or on bronchodilators) Will participate in a physical activity intervention or exercise program Competent to provide informed consent Willingness to make return visits and be available by telephone for duration of study Exclusion Criteria: Female sex Claustrophobia History of seizures Known brain lesion Current diagnosis of bipolar disorder, schizophrenia, or psychotic disorder Cognitive disorder such as dementia Known metal in body including: shrapnel surgical medical clips implants pacemakers metal-based tattoos

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Veterans with COPD<br>Veterans with COPD who will participate in a physical activity intervention or exercise program | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortical thickness | Cortical thickness will be measured by brain MRIs that will assess functional connectivity and structural variables. Cortical thickness will be reported in millimeters. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Pain, Dyspnea, Neuroimaging, Functional Connectivity