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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Veterans with COPD | Veterans with COPD who will participate in a physical activity intervention or exercise program |
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| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Exercise Capacity | measured by the 6-minute walk test | 3 months |
| Physical Activity | Measured by daily step counts | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Pain Intensity | Pain intensity will be measured with the Brief Pain Index. The Brief Pain Index rates pain intensity on a numbered scale of 0 - 10, with higher scores indicating more pain. | 3 months |
| Dyspnea |
Inclusion Criteria:
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:
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Veterans with COPD
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| Name | Affiliation | Role |
|---|---|---|
| Marilyn L. Moy, MD | VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA | Boston | Massachusetts | 02130-4817 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Veterans With COPD | Veterans with COPD who will participate in a physical activity intervention or exercise program |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Veterans With COPD | Veterans with COPD who will participate in a physical activity intervention or exercise program |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Numbers do not match baseline numbers because of missing data. Participants may have completed only some assessments or did not have follow-up assessments. | Posted | Mean | Standard Deviation | mm | 3 months |
|
|
Duration of the study from enrollment to follow-up of approximately 3 months for each participant.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Veterans With COPD | Veterans with COPD who will participate in a physical activity intervention or exercise program |
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Small sample size with missing data
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marilyn Moy, MD, MSc | VA Boston Healthcare System | 857-203-6622 | marilyn.moy@va.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 2, 2021 | Jun 30, 2025 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 14, 2022 | Jun 13, 2024 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D010146 | Pain |
| D004417 | Dyspnea |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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None retained
Dyspnea will be measured with the modified Medical Research Council scale from 0 to 4 where a higher score means greater dyspnea.
| 3 months |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Cortical thickness | Mean | Standard Deviation | mm |
|
| Pain | Pain intensity will be measured with the Brief Pain Index. The Brief Pain Index rates pain intensity on a numbered scale of 0 - 10, with higher scores indicating more pain. | 6 participants did not complete questionnaire at baseline | Mean | Standard Deviation | units on a scale |
|
| Dyspnea | Dyspnea will be measured with the modified Medical Research Council scale from 0 to 4 where a higher score means greater dyspnea. | 1 missing value | Mean | Standard Deviation | units on a scale |
|
| Exercise capacity | Exercise capacity assessed by the 6-minute walk test where participant is asked to walk and cover as much ground as possible in 6 minutes. This is a validated test in patients with COPD. 4 missing values | Mean | Standard Deviation | feet |
|
| Physical Activity | 4 missing participants | Mean | Standard Deviation | steps per day |
|
|
|
| Secondary | Exercise Capacity | measured by the 6-minute walk test | Numbers do not match baseline numbers because of missing data. Participants may have completed only some assessments or did not have follow-up assessments. | Posted | Mean | Standard Deviation | feet | 3 months |
|
|
|
| Secondary | Physical Activity | Measured by daily step counts | Numbers do not match baseline numbers because of missing data. Participants may have completed only some assessments or did not have follow-up assessments. | Posted | Mean | Standard Deviation | steps per day | 3 months |
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| Other Pre-specified | Pain Intensity | Pain intensity will be measured with the Brief Pain Index. The Brief Pain Index rates pain intensity on a numbered scale of 0 - 10, with higher scores indicating more pain. | Numbers do not match baseline numbers because of missing data. Participants may have completed only some assessments or did not have follow-up assessments. | Posted | Mean | Standard Deviation | units on a scale | 3 months |
|
|
|
| Other Pre-specified | Dyspnea | Dyspnea will be measured with the modified Medical Research Council scale from 0 to 4 where a higher score means greater dyspnea. | Numbers do not match baseline numbers because of missing data. Participants may have completed only some assessments or did not have follow-up assessments. | Posted | Mean | Standard Deviation | units on a scale | 3 months |
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| 9 |
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| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D012120 | Respiration Disorders |
| D012818 | Signs and Symptoms, Respiratory |