NCT06574165 · VA Office of Research and Development
Relationships of Affect and Neuroinflammation With Clinical Pain in Veterans With Fibromyalgia
(RAN)
What this study is about
Fibromyalgia (FM) is a chronic pain condition that disproportionately impacts Veterans. Individuals diagnosed with FM patients experience lower self-esteem and positive affect, as well as greater levels of depression, anxiety, negative affect, and pain catastrophizing.
View original scientific description
Fibromyalgia (FM) is a chronic pain condition that disproportionately impacts Veterans. Individuals diagnosed with FM patients experience lower self-esteem and positive affect, as well as greater levels of depression, anxiety, negative affect, and pain catastrophizing. Among those experiencing FM, clinical and experimental pain are associated with specific dispositional trait profiles, which are indexed by levels of negative affect and positive affect. Neuroinflammation and inflammation also play a role in FM- related affect and pain. Recent studies that have highlighted neuroinflammation and inflammation as physiological mechanisms associated with changes in dysregulated affect and chronic pain. Veterans with FM can ameliorate dispositional traits-i.e., increasing positive affect and reducing negative affect-by participating in exercise. However, a gap exists regarding how to optimally engage Veterans with FM in an exercise program. Thus, to fully take advantage of all potential therapeutic benefits of exercise for FM, there is a critical need to identify those factors underlying exercise engagement for FM pain management. The purpose for this study is to 1) determine associations of dispositional trait styles, neuroinflammation, and inflammation with pain outcomes in Veterans with FM; and 2) develop and design a Veteran-informed exercise program.
Interventions
BEHAVIORAL
Moderate Intensity Continuous Training
6-week structured exercise intervention. The intervention will include twice weekly, center-based, aerobic exercise consisting of continuous treadmill walking. Each center-based session will include 45 minutes of aerobic exercise in addition to balance and flexibility exercises to promote cool-down. During each exercise session, participants will also be asked to wear a heart rate monitor to measure mean pulse during exercise sessions.
Primary outcome measures
Dispositional Trait Styles
Time frame: Baseline to 12 weeks
As a measurement of affect, participants will complete the Positive and Negative Affect Schedule and indicate the frequency with which the participants generally experience 10 positive (i.e., interested, excited) and 10 negative (i.e., distressed, upset) feelings. Items are rated ranging from 1 (very slightly or not at all) to 5 (extremely) with a total subscale ranging from 10 to 50.
Feasibility
Time frame: Baseline to 12 weeks
Feasibility will be percentage of exercise sessions attended.
Clinical Pain Severity
Time frame: Baseline to 12 weeks
Participants will self-report a number between 0-100 describing the intensity of pain, such that 0= no pain and 100 = the most intense pain imaginable. Any integer from 0 to 100 can be provided.
Pain Threshold
Time frame: Baseline to 12 weeks
Pain threshold refers to the intensity at which a stimulus is first perceived as painful. Pressure stimuli will be delivered to the participant's forearm and lower back using a handheld pressure algometer. The pressure will gradually increase until the participant responds by pressing a button on a handheld device. For pressure threshold, participants will be instructed to press the button when the sensation "first becomes painful."
Temporal Summation of Pain
Time frame: Baseline to 12 weeks
Temporal summation refers to a form of endogenous pain facilitation characterized by the perception of increased pain despite constant or even reduced peripheral afferent input. Temporal summation is presumed to be the psychosocial manifestation of wind-up. Wind-up is a phenomenon where repetitive stimulation of C primary afferents at rates greater that 0.3 Hertz produces a slowly increasing response of second-order neurons in the spinal cord. Temporal summation will be assessed using a nylon monofilament calibrated to bend a 300g of pressure on the back of the hand and lower back. Participants will be instructed to provide a verbal 0-100 rating of pain following a single contact of the monofilament. Then, participants will be instructed to provide another 0-100 rating of pain following a series of 10 contacts of the monofilament. This procedure will repeated twice at each location and pain ratings will be averaged across the two trials.
Conditioned Pain Modulation
Time frame: Baseline to 12 weeks
A routinely used quantitative sensory testing protocol for the measurement of endogenous pain inhibition is conditioned pain modulation, which refers to the reduction in pain from one stimulus (the test stimulus) produced by the application of a second pain stimulus at a remote body site (the conditioning stimulus). Conditioned pain modulation is believed to reflect the perceptual manifestation of diffuse noxious inhibitory controls, whereby ascending projections from one noxious stimulus activate supraspinal structures that trigger descending inhibitory projections to the dorsal horn. Participants will undergo four cold pressor immersions that consists of placing the non-dominant hand, up to the wrist, into circulating cold water for up to 1 minute and will provide a 0-100 rating of pain. Following each immersion, a handheld force algometer will be applied to either the forearm or lower back and press a handheld button to indicate when the pressure first becomes painful.
C-reactive protein
Time frame: Baseline to 12 weeks
A marker of pro-inflammation from blood draws
Tumor necrosis factor- alpha
Time frame: Baseline to 12 weeks
A marker of pro-inflammation from blood draws
Interleukin-6
Time frame: Baseline to 12 weeks
A marker of pro-inflammation from blood draws
Interleukin- 10
Time frame: Baseline to 12 weeks
A marker of pro-inflammation from blood draws
Interleukin- 8
Time frame: Baseline to 12 weeks
A marker of pro-inflammation from blood draws
Myo-inositol
Time frame: Baseline to 12 weeks
marker of neuroinflammation measured via magnetic resonance spectroscopy imaging.
N-acetylaspartate
Time frame: Baseline to 12 weeks
marker of neuroinflammation measured via magnetic resonance spectroscopy imaging.
Choline
Time frame: Baseline to 12 weeks
marker of neuroinflammation measured via magnetic resonance spectroscopy imaging.
Lactate
Time frame: Baseline to 12 weeks
marker of neuroinflammation measured via magnetic resonance spectroscopy imaging.
Creatine
Time frame: Baseline to 12 weeks
marker of neuroinflammation measured via magnetic resonance spectroscopy imaging.
Brain Temperature
Time frame: Baseline to 12 weeks
marker of neuroinflammation using absolute brain temperatures (in °C) from magnetic resonance spectroscopy imaging.
Exercise Benefits and Barriers
Time frame: Baseline to 12 weeks
Participants will be asked to complete the Exercise Barriers and Benefits Scale that assesses perceived benefits and barriers to exercise to rank agreement with 29 statements, where 4='strongly agree' and 1='strongly disagree.'
Exercise Perceptions
Time frame: Baseline to 12 weeks
Semi-structured interviews will be conducted around topics related to current exercise behavior and any barriers the participants have to current exercise behavior, and will elicit participants' views on what an ideal exercise program would be.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Widespread pain index (WPI) 7 and symptom severity scale (SSS) score 5 OR WPI 4-6 and SSS score 9
- Generalized pain, defined as pain in at least 4 of 5 regions, is present
- Symptoms have been present at a similar level for at least 3 months
- A diagnosis of FM is valid irrespective of other diagnoses. A diagnosis of FM does not exclude the presence of other clinically important illnesses
- PTSD Checklist-Stressor-Specific Version 1 re-experiencing (intrusion) symptom, 3 avoidance (numbing) symptoms, and 2 hyperarousal symptoms, each present at the level of moderate or higher during the past month, and if the total severity score is 50 or higher Inclusion Criteria for Veterans living without FM:
- Age-matched to participant with FM
Exclusion criteria
- Neurological disorder
- Body mass index \> 40
- Chronic kidney disease
- Severe cardiac condition (chronic heart failure, stenosis, history of cardiac arrest, defibrillator, angina)
- Ischemic heart disease
- 90 days of daily opioid use
- Beta-blocker
- Inability to consent for study participation (9) Significant cognitive impairment, defined as a known diagnosis of dementia (10) MRI contraindications (11) Pregnancy Exclusion Criteria for Veterans living without FM:
- Active use of medications affecting pain responses
- Neurological disorder
- Body mass index \> 40
- MRI contraindications
Where
- Birmingham, Alabama
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Oct 28, 2025 · Source of record for eligibility and locations