An interventional study of Repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy in Chronic Pain and Depression, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Per ClinicalTrials.gov, last updated 2026-07-17.
Sponsored by VA Office of Research and Development · Not applicable, Interventional, and Treatment
Veterans with comorbid chronic pain and depression are highly prevalent, have poor functional status and low quality of life, are at increased risk of suicide and lack access to effective treatments. To address this problem, the proposed research will examine the feasibility of a novel approach that integrates repetitive Transcranial Magnetic Stimulation and Acceptance and Commitment Therapy with the overall goal of maximizing functional improvement in Veterans with chronic pain and depression. This is an important first-step in preparation for a future randomized efficacy trial. The investigators will also include two cognitive control tasks with concurrent electroencephalography to explore as a potential objective indicator of treatment response. This application addresses a critical need within the Veterans Health Administration and is closely aligned with the focus area of developing suicide prevention treatments that influence participation in life roles.
Comorbid depression is highly prevalent in Veterans with chronic pain and contributes to greater pain severity, functional impairment, and suicide risk relative to those with chronic pain alone. Despite the well-known association between chronic pain and depression, current treatments fall short of producing meaningful improvements in function and quality of life in this population. In this application, the investigators propose to address this problem by a novel intervention that combines repetitive Transcranial Magnetic Stimulation (rTMS) and Acceptance and Commitment Therapy (ACT).
ACT is an evidence-based psychosocial intervention that improves function in Veterans with chronic pain. However, similar to the broader literature, comorbid depression significantly limits the efficacy of ACT, which may be directly related to dysfunctional brain circuits that maintain depression. rTMS is a non-invasive brain stimulation intervention that is FDA-cleared for the treatment of depression. The most commonly targeted stimulation area is the left dorsolateral prefrontal cortex (DLFPC), a prefrontal brain region involved in cognitive control and emotion regulation. rTMS over the left DLPFC has also been used to reduce pain intensity in patients with chronic pain, as the DLPFC is implicated in the affective processing of painful stimuli. Importantly, while rTMS has been shown to reduce depression severity and pain intensity, it does not directly address function. Thus, the proposed research will integrate rTMS and ACT with the goal of maximizing functional improvement in Veterans with chronic pain and depression.
The purpose of this application is to examine the feasibility of a future randomized efficacy trial. A total of 24 Veterans with chronic pain and depression will be randomized into DLPFC-rTMS + ACT or sham-rTMS + ACT conditions. Multiple metrics of feasibility will be assessed, including general interest in the study, willingness to participate, enrollment, retention, drop-out, number of adverse events, and participant blindness to condition, as well as ratings of credibility, expectation, and treatment satisfaction. The investigators will also estimate the preliminary impact of DLPFC-rTMS + ACT and sham-rTMS + ACT on function as measured by reductions in pain interference (primary clinical outcome). The intent of preliminary analyses is to obtain an additional indicator for a future large-scale trial, not to verify group differences. Further, the investigators will include two cognitive control tasks, the Emotion Distractor and Attention-to-Breath tasks, with concurrent EEG recording as a potential objective indicator of treatment response. The study team has previously demonstrated the association between depression severity and DLPFC activity on these tasks. In the proposed study, the investigators will explore the associations between treatment-related change in DLPFC activity and treatment outcomes.
Veterans with chronic pain and depression do not have access to effective treatments. To address this need, the investigators seek to examine the feasibility of a novel approach by integrating a somatic and a psychosocial intervention. The investigator's scientific premise is that rTMS over the left DLPFC will remediate hypofunction of prefrontal brain circuits that is necessary to maximize the impact of ACT on function in Veterans with chronic pain and depression. Findings from the proposed research have the potential of substantially increasing the physical and psychosocial functioning of Veterans with chronic pain and depression.
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Exclusion Criteria:
Active DLPFC-rTMS with ACT treatment
Device: Repetitive Transcranial Magnetic Stimulation · Behavioral: Acceptance and Commitment Therapy
Sham delivered rTMS with ACT treatment
Behavioral: Acceptance and Commitment Therapy
rTMS is a non-invasive brain stimulation technique designed to alter network function
Also known as: rTMS
ACT is a mindfulness-based cognitive behavioral intervention that has demonstrated efficacy for chronic pain.
Also known as: ACT
PROMIS Pain Interference Change
The PROMIS Pain Interference questionnaire consists of 8-items that assess the degree to which pain interferes with various aspects of life, including mobility, social activity, and mood. Items are scored on a 1 ("Not at all") to 5 ("Very much") scale with a range of 8 - 40. These scores are subsequently transcribed to a T-score. PROMIS measures are reported as standardized T-scores with a population mean of 50 and standard deviation of 10. Higher scores indicate greater pain interference. A 10-point difference represents one standard deviation from the reference population mean.
Time frame: Baseline, weekly during ACT intervention, 9 weeks (post-treatment) for total of 10 timepoints
Patient Health Questionnaire-9 Change
The PHQ-9 is a widely used measure of depressive symptoms. Items are scored on a 0 ("not at all") to 3 ("Nearly every day") scale with a range of 0 - 27. Higher scores indicate greater depression severity.
Time frame: Baseline, weekly during ACT intervention, 9 weeks (post-treatment) for total of 10 timepoints
PROMIS Pain Intensity Change
The PROMIS Pain Intensity questionnaire consists of 3 items assessing worst and average pain over the past week, as well as current pain. Items are scored on a 1 ("No pain") to 5 ("Very severe") scale with a range of 3 - 15. Total scores are subsequently converted to T-scores. PROMIS measures are reported as standardized T-scores with a population mean of 50 and standard deviation of 10. Higher scores indicate greater pain intensity. A 10-point difference represents one standard deviation from the reference population mean.
Time frame: Baseline, weekly during ACT intervention, 9 weeks (post-treatment) for total of 10 timepoints
Enrollment began in May 2023 and concluded in February 2025. Participants were recruited via study flyer and referral from the Neuromodulation Program, Mental Health, Behavioral Medicine, and Primary Care clinics at VA San Diego Healthcare System.
| Milestone | DLPFC-TMS + ACT | Sham-TMS + ACT |
|---|---|---|
| Started | 10 | 9 |
| Completed | 10 | 9 |
| Not completed | 0 | 0 |
The PROMIS Pain Interference questionnaire consists of 8-items that assess the degree to which pain interferes with various aspects of life, including mobility, social activity, and mood. Items are scored on a 1 ("Not at all") to 5 ("Very much") scale with a range of 8 - 40. These scores are subsequently transcribed to a T-score. PROMIS measures are reported as standardized T-scores with a population mean of 50 and standard deviation of 10. Higher scores indicate greater pain interference. A 10-point difference represents one standard deviation from the reference population mean.
| T-score | DLPFC-rTMS + ACT | Sham-rTMS + ACT |
|---|---|---|
| Baseline | 68.54 ± 6.89 | 66.30 ± 6.85 |
| Week 1 | 66.51 ± 4.50 | 59.67 ± 8.76 |
| Week 2 | 65.00 ± 5.22 | 60.62 ± 5.36 |
| Week 3 | 66.20 ± 5.71 | 60.50 ± 7.10 |
| Week 4 | 66.18 ± 6.96 | 58.59 ± 8.46 |
| Week 5 | 63.85 ± 6.03 | 58.33 ± 6.30 |
| Week 6 | 63.32 ± 6.31 | 57.81 ± 7.51 |
| Week 7 | 62.36 ± 7.14 | 56.33 ± 7.34 |
| Week 8 | 63.23 ± 7.34 | 56.07 ± 7.35 |
| Week 9, Post-treatment | 65.57 ± 7.85 | 57.13 ± 8.07 |
The PHQ-9 is a widely used measure of depressive symptoms. Items are scored on a 0 ("not at all") to 3 ("Nearly every day") scale with a range of 0 - 27. Higher scores indicate greater depression severity.
| units on a scale | DLPFC-rTMS + ACT | Sham-rTMS + ACT |
|---|---|---|
| Baseline | 16.80 ± 5.05 | 13.44 ± 4.93 |
| Week 1 | 15.00 ± 5.12 | 10.89 ± 5.01 |
| Week 2 | 15.10 ± 5.57 | 9.78 ± 4.02 |
| Week 3 | 13.20 ± 5.53 | 12.00 ± 5.94 |
| Week 4 | 15.60 ± 5.17 | 11.11 ± 4.51 |
| Week 5 | 13.30 ± 5.50 | 9.89 ± 3.76 |
| Week 6 | 12.67 ± 6.42 | 8.78 ± 5.19 |
| Week 7 | 11.63 ± 6.95 | 9.50 ± 3.57 |
| Week 8 | 11.56 ± 6.23 | 7.67 ± 3.97 |
| Week 9, post-treatment | 12.20 ± 6.13 | 8.00 ± 3.71 |
The PROMIS Pain Intensity questionnaire consists of 3 items assessing worst and average pain over the past week, as well as current pain. Items are scored on a 1 ("No pain") to 5 ("Very severe") scale with a range of 3 - 15. Total scores are subsequently converted to T-scores. PROMIS measures are reported as standardized T-scores with a population mean of 50 and standard deviation of 10. Higher scores indicate greater pain intensity. A 10-point difference represents one standard deviation from the reference population mean.
| T-score | DLPFC-rTMS + ACT | Sham-rTMS + ACT |
|---|---|---|
| Baseline | 56.20 ± 5.01 | 55.33 ± 3.33 |
| Week 1 | 56.19 ± 6.81 | 54.17 ± 4.10 |
| Week 2 | 53.23 ± 7.17 | 51.60 ± 4.46 |
| Week 3 | 55.15 ± 5.51 | 50.24 ± 6.74 |
| Week 4 | 56.43 ± 6.85 | 48.96 ± 6.67 |
| Week 5 | 56.06 ± 5.25 | 49.76 ± 6.08 |
| Week 6 | 55.06 ± 4.55 | 48.41 ± 5.76 |
| Week 7 | 54.99 ± 6.14 | 49.44 ± 5.43 |
| Week 8 | 54.82 ± 7.48 | 48.78 ± 6.28 |
| Week 9, post-treatment | 56.02 ± 8.86 | 48.46 ± 6.73 |
Collected over Adverse events were assessed at each rTMS session, up to 9 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| DLPFC-rTMS + ACT | 0/10 (0%) | 0/10 (0%) | 6/10 (60%) |
| Sham-rTMS + ACT | 0/9 (0%) | 0/9 (0%) | 7/9 (77.8%) |
| Event | DLPFC-rTMS + ACT | Sham-rTMS + ACT |
|---|---|---|
| HeadacheGeneral disorders | 5/10 | 4/9 |
| FatigueGeneral disorders | 3/10 | 1/9 |
| Tingling around TMS stimulation siteGeneral disorders | 1/10 | 2/9 |
| NauseaGeneral disorders | 0/10 | 2/9 |
| Muscle SorenessMusculoskeletal and connective tissue disorders | 2/10 | 1/9 |
| Eye twitchGeneral disorders | 2/10 | 0/9 |
| Ringing in earsGeneral disorders | 0/10 | 1/9 |
| DepressionPsychiatric disorders | 0/10 | 1/9 |
| DiarrheaGastrointestinal disorders | 0/10 | 1/9 |
| ToothacheGeneral disorders | 0/10 | 1/9 |
| Age, Continuous(Years of age) | DLPFC-rTMS + ACT | Sham-rTMS + ACT | Total |
|---|---|---|---|
| Mean | 43.90 ± 10.75 | 42.00 ± 13.07 | 43.00 ± 11.61 |
| Sex: Female, Male(Participants) | DLPFC-rTMS + ACT | Sham-rTMS + ACT | Total |
|---|---|---|---|
| Female | 4 | 3 | 7 |
| Male | 6 | 6 | 12 |
| Race (NIH/OMB)(Participants) | DLPFC-rTMS + ACT | Sham-rTMS + ACT | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 1 | 2 | 3 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 1 |
| White | 8 | 4 | 12 |
| More than one race | 0 | 1 | 1 |
| Unknown or Not Reported | 1 | 1 | 2 |
| Ethnicity (NIH/OMB)(Participants) | DLPFC-rTMS + ACT | Sham-rTMS + ACT | Total |
|---|---|---|---|
| Hispanic or Latino | 2 | 0 | 2 |
| Not Hispanic or Latino | 8 | 9 | 17 |
| Unknown or Not Reported | 0 | 0 | 0 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — A data repository will be created upon completion of the study. Data obtained in this study that has scientific value to other qualified researchers will made available upon request. Interested researches will be able to access de-identified data through a Data Use Agreement.
Supporting information: Study protocol, Sap, Analytic code
This study is completed, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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