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CompletedNCT04291131BRAIN-SPAUpdated Aug 15, 2025Results posted

BRAIN, Symptoms, and Physical Activity in COPD

An observational study in COPD and Chronic Musculoskeletal Pain, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to male participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2025-08-15.

Sponsored by VA Office of Research and Development · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
9
Ages
40 Years and older
Sex
Male
01

Study summary

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.

Read the detailed description

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).

02

Conditions studied

  • COPD
  • Chronic Musculoskeletal Pain

Keywords

  • COPD
  • Pain
  • Dyspnea
  • Neuroimaging
  • Functional Connectivity
03

In context

Pulmonary Disease, Chronic Obstructive

4,131 studies on the registry are indexed under Pulmonary Disease, Chronic Obstructive; 697 are open to participants now.

This study's enrollment of 9 is below the median of 180 across 1,066 observational studies indexed under Pulmonary Disease, Chronic Obstructive.

Browse Pulmonary Disease, Chronic Obstructive studies →

Lead sponsor

VA Office of Research and Development is the lead sponsor of 1,733 studies on the registry; 396 are open to participants now.

Of its 206 completed or terminated interventional studies of FDA-regulated products, 180 (87%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Veterans with COPD

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

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
05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
9 participants (actual)
Patient registry
No
Biospecimen retention
None retained

Groups and cohorts

  • Veterans with COPD

    Veterans with COPD who will participate in a physical activity intervention or exercise program

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 3 months

Secondary outcomes

  1. Exercise Capacity

    measured by the 6-minute walk test

    Time frame: 3 months

  2. Physical Activity

    Measured by daily step counts

    Time frame: 3 months

Other outcomes

  1. 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.

    Time frame: 3 months

  2. Dyspnea

    Dyspnea will be measured with the modified Medical Research Council scale from 0 to 4 where a higher score means greater dyspnea.

    Time frame: 3 months

07

Results

Posted Aug 15, 2025
Limitations and caveats
Small sample size with missing data

Participant flow

Participant flow — Overall Study
MilestoneVeterans With COPD
Started9
Completed6
Not completed3

Outcome measures

PrimaryCortical Thickness

Cortical thickness will be measured by brain MRIs that will assess functional connectivity and structural variables. Cortical thickness will be reported in millimeters.

Time frame:
3 months
Reported as:
Mean · mm
Cortical Thickness
mmVeterans With COPD
Cortical Thickness2.2 ± 0.06
SecondaryExercise Capacity

measured by the 6-minute walk test

Time frame:
3 months
Reported as:
Mean · feet
Exercise Capacity
feetVeterans With COPD
Exercise Capacity1410 ± 80
SecondaryPhysical Activity

Measured by daily step counts

Time frame:
3 months
Reported as:
Mean · steps per day
Physical Activity
steps per dayVeterans With COPD
Physical Activity4835 ± 3226
Other pre-specifiedPain 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.

Time frame:
3 months
Reported as:
Mean · units on a scale
Pain Intensity
units on a scaleVeterans With COPD
Pain Intensity4 ± 1.41
Other pre-specifiedDyspnea

Dyspnea will be measured with the modified Medical Research Council scale from 0 to 4 where a higher score means greater dyspnea.

Time frame:
3 months
Reported as:
Mean · units on a scale
Dyspnea
units on a scaleVeterans With COPD
Dyspnea1.83 ± 1.47

Adverse events

Collected over Duration of the study from enrollment to follow-up of approximately 3 months for each participant.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Veterans With COPD0/9 (0%)0/9 (0%)0/9 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Veterans With COPD
<=18 years0
Between 18 and 65 years2
>=65 years7
Age, Continuous
Age, Continuous(years)Veterans With COPD
Mean73 ± 6
Sex: Female, Male
Sex: Female, Male(Participants)Veterans With COPD
Female0
Male9
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Veterans With COPD
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White9
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(Participants)Veterans With COPD
United States9
Cortical thickness
Cortical thickness(mm)Veterans With COPD
Mean2.24 ± 0.1
Pain
Pain(units on a scale)Veterans With COPD
Mean4 ± 3
Dyspnea
Dyspnea(units on a scale)Veterans With COPD
Mean2.38 ± 1.3

2 further baseline measures are reported on the registry.

08

Study locations

1 site
  • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
    Boston, Massachusetts 02130-4817, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Aug 2, 2021
  • Informed consent form · Mar 14, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 15, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04291131
Lead sponsor
VA Office of Research and Development
Responsible party
Sponsor
First posted
Mar 2, 2020
Start date
Jul 1, 2020
Primary completion
Jun 30, 2024
Completion
Jun 30, 2024
Results posted
Aug 15, 2025
Last update
Aug 15, 2025

Study contacts

Marilyn L. Moy, MD
principal investigator · VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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