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Chronic pain is highly prevalent in patients with opioid use disorder on methadone maintenance therapy, and associated with problems related to psychosocial functioning, medical and psychiatric health, and substance craving and use. Neuroimaging has strongly correlated pain processing with the medial prefrontal and dorsal anterior cingulate cortices. This study will investigate the effects of repetitive transcranial magnetic stimulation (rTMS) using the H7 coil targeting these same brain areas for the treatment of chronic pain in patients on methadone maintenance therapy,and magnetic resonance imaging and spectroscopy (MRI/MRS) will be used to evaluate target engagement and mechanism.
The research aims of this study are to (1) investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) of the medial prefrontal cortex and dorsal anterior cingulate cortex for the treatment of chronic non-cancer pain in participants with opioid use disorder on methadone-maintenance therapy, and (2) investigate target engagement by measuring changes in gray matter volume and glutamate-glutamine in these brain regions by magnetic resonance imaging and spectroscopy. Given the high incidence of chronic pain in the OUD population and specifically the methadone-maintained population, there is great need for effective treatments. Untreated chronic pain contributes to medical and psychiatric problems, reduced quality of life, and increased risk of substance use and overdose. Non-invasive neuromodulation like rTMS, which is currently FDA-approved for treatment-resistant depression and OCD, holds promise as a safe and effective therapeutic. This project will investigate rTMS of brain regions known to process the affective and cognitive components of chronic pain, utilizing a treatment protocol modeled after the FDA-approved protocol for obsessive-compulsive disorder.
Volunteers will be randomized in a double-blind manner to 25 sessions (5 weeks) of either active high-frequency rTMS or sham stimulation. Participants will regularly complete measures to evaluate changes in pain severity and interference. The primary clinical outcome measures will be pain severity and interference scores on the Brief Pain Inventory (BPI). Additionally, participants will undergo MRI/MRS scans before and after the 5 weeks of rTMS to evaluate target engagement and help elucidate the potential mechanism of action of the intervention.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active rTMS stimulation | Active Comparator | This arm will receive high-frequency rTMS pulses directed at the medial prefrontal and anterior cingulate cortices. |
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| Sham rTMS stimulation | Sham Comparator | The sham coil setting is designed to mimic the auditory artifact and the scalp sensations evoked by the real coil and to produce activation of facial muscles similar to the effect of active rTMS without stimulating the brain itself. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active rTMS treatment | Device | In the active treatment, magnetic power output will be delivered to the participants through the coils. |
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| Measure | Description | Time Frame |
|---|---|---|
| Feasibility: Ability to Recruit and to Have Participants Complete the Study | Number of participants with chronic pain and comorbid psychiatric disorders who complete 60% of sessions. | 3 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Diana Martinez, MD | New York Sate Psychiatric Institute / Columbia University | Principal Investigator |
| Derek Blevins, MD | New York State Psychiatric Institute / Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Substance Treatment and Research Service (STARS) | New York | New York | 10019 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Active rTMS Stimulation | This arm will receive high-frequency rTMS pulses directed at the medial prefrontal and anterior cingulate cortices. Active rTMS treatment: In the active treatment, magnetic power output will be delivered to the participants through the coils. |
| FG001 | Sham rTMS Stimulation | The sham coil setting is designed to mimic the auditory artifact and the scalp sensations evoked by the real coil and to produce activation of facial muscles similar to the effect of active rTMS without stimulating the brain itself. Sham rTMS treatment: The sham coil setting is designed to mimic the auditory artifact and the scalp sensations evoked by the real coil, and to produce activation of facial muscles similar to the effect of a real H coil, without stimulating the brain itself. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Active rTMS Stimulation | This arm will receive high-frequency rTMS pulses directed at the medial prefrontal and anterior cingulate cortices. Active rTMS treatment: In the active treatment, magnetic power output will be delivered to the participants through the coils. |
| BG001 | Sham rTMS Stimulation |
| 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 | Feasibility: Ability to Recruit and to Have Participants Complete the Study | Number of participants with chronic pain and comorbid psychiatric disorders who complete 60% of sessions. | In this feasibility study all participants were included in determining feasibility. | Posted | Count of Participants | Participants | 3 months |
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Participants were followed for 9 weeks.
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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 | Active rTMS Stimulation | This arm will receive high-frequency rTMS pulses directed at the medial prefrontal and anterior cingulate cortices. Active rTMS treatment: In the active treatment, magnetic power output will be delivered to the participants through the coils. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| headache | Nervous system disorders | SNOMED CT | Non-systematic Assessment | Mild headache reported with TMS (both groups) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Diana Martinez | Columbia Univeristy | 646-774-6160 | dm437@cumc.columbia.edu |
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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 | Jul 10, 2022 | Mar 11, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D059350 | Chronic Pain |
| D009293 | Opioid-Related Disorders |
| ID | Term |
|---|---|
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Sham rTMS treatment | Device | The sham coil setting is designed to mimic the auditory artifact and the scalp sensations evoked by the real coil, and to produce activation of facial muscles similar to the effect of a real H coil, without stimulating the brain itself. |
|
The sham coil setting is designed to mimic the auditory artifact and the scalp sensations evoked by the real coil and to produce activation of facial muscles similar to the effect of active rTMS without stimulating the brain itself. Sham rTMS treatment: The sham coil setting is designed to mimic the auditory artifact and the scalp sensations evoked by the real coil, and to produce activation of facial muscles similar to the effect of a real H coil, without stimulating the brain itself. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
The sham coil setting is designed to mimic the auditory artifact and the scalp sensations evoked by the real coil and to produce activation of facial muscles similar to the effect of active rTMS without stimulating the brain itself.
Sham rTMS treatment: The sham coil setting is designed to mimic the auditory artifact and the scalp sensations evoked by the real coil, and to produce activation of facial muscles similar to the effect of a real H coil, without stimulating the brain itself.
|
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| 0 |
| 4 |
| 0 |
| 4 |
| 2 |
| 4 |
| EG001 | Sham rTMS Stimulation | The sham coil setting is designed to mimic the auditory artifact and the scalp sensations evoked by the real coil and to produce activation of facial muscles similar to the effect of active rTMS without stimulating the brain itself. Sham rTMS treatment: The sham coil setting is designed to mimic the auditory artifact and the scalp sensations evoked by the real coil, and to produce activation of facial muscles similar to the effect of a real H coil, without stimulating the brain itself. | 0 | 3 | 0 | 3 | 2 | 3 |
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| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |