Transcranial Magnetic Stimulation for Treating Women With Chronic Widespread Pain

Study Overview
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Brief Summary
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While acute pain after surgery or trauma comes on suddenly and lasts for a limited amount of time, chronic pain persists and can continue for months and even years. Repetitive transcranial magnetic stimulation (rTMS) uses a magnetic field to deliver a current to the brain and can affect brain activity. The purpose of this study is to determine the effectiveness of rTMS treatment in reducing chronic widespread pain in women.

Detailed Description
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Chronic widespread pain is characterized by musculoskeletal pain that lasts for at least 3 months, pain above and below the waist, pain on both the right and left sides, and pain in the head, neck, spine, or back. In addition to fatigue, chronic widespread pain is a hallmark feature of fibromyalgia. Significant physical and emotional effects usually accompany chronic widespread pain and fibromyalgia, making the development of effective treatments a priority. rTMS involves a neurophysiologic technique that directs a current into the brain by using a magnetic field to pass the scalp and skull safely and painlessly. Stimuli are applied to the same brain area several times per second during several consecutive seconds. rTMS has been found to be effective for treating certain types of chronic pain. The purpose of this study is to determine the effectiveness of rTMS treatment in reducing bodily pain associated with chronic widespread pain and/or fibromyalgia in women. Participants in this study will undergo a diagnostic interview, physical and neurological exam, electrocardiogram, magnetic resonance imaging, and blood and urine collection for screening purposes. Eligible participants will then be randomly assigned to receive either rTMS treatment or sham rTMS treatment. One-hour daily treatment sessions will occur over 15 days. After every five treatment sessions, participants will be interviewed about their pain and depression symptoms, and they will fill out questionnaires about pain, depression, fatigue, sleep, and exercise. Participants will also undergo pain threshold and tolerance testing of their right thumb. On a daily basis, participants will rate their level of pain using a 0 to 20 scale. Follow-up evaluations will occur 1, 4, and 12 weeks after treatment and will include a repeat interview and testing. After the follow-up evaluations, any participants who did not respond to the sham treatment will be offered a series of 15 real rTMS treatment sessions.

Official Title
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Transcranial Magnetic Stimulation (TMS) in the Treatment of Chronic Widespread Pain (CWP)

Conditions
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Fibromyalgia, Chronic Pain, Depression

Intervention / Treatment
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* Device: rTMS
* Device: Sham rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of chronic widespread pain as defined by the 1990 American College of Rheumatology guidelines: chronic musculoskeletal pain for at least 3 months; pain above and below the waist; pain on both right and left sides; pain at one axial site (e.g., head, neck, spine, or back) Willing to remain on a stable medical regimen during the entire 6-week course of Phase 1 treatment and 8 weeks prior to rTMS treatment Willing to undergo random assignment and able to attend treatment sessions Willing to remain on a stable psychotherapy regimen if currently receiving psychotherapy that has been ongoing for at least 3 months prior to study entry Exclusion Criteria: Unable to maintain treatment as usual at stable doses for any medical or psychiatric conditions for 8 weeks prior to and during the study Another medical condition associated with significant pain (e.g., diabetic neuropathy, systemic lupus erythematosus, Rheumatoid arthritis, severe degenerative joint disease) Any condition that might increase the risk of seizures from TMS History of a seizure disorder or family history of a seizure disorder Previous use of TMS Involvement in litigation or disability that is related to fibromyalgia, chronic widespread pain, or depression Current use of proconvulsant medications (e.g., bupropion) Metal in the body that would prevent magnetic resonance imaging (MRI) or TMS (e.g., aneurysm clips, pacemakers, neurostimulators) History of head injury associated with loss of consciousness for more than 15 minutes, brain surgery, or lithium toxicity History of bipolar disorder, schizophrenia, obsessive compulsive disorder, panic disorder, or post-traumatic stress disorder Current substance abuse or dependence Active suicidal intent or plan Severe claustrophobia that would prevent MRI Major depression with psychotic features or a current major depressive episode lasting longer than 5 years Pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active rTMS<br>Active rTMS involves administration of real rTMS to the patient. | Device: rTMS<br>* 10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions at 120% motor threshold rTMS to left dorsolateral prefrontal cortex<br>* Other names: Neuronetics 2100 CRS rTMS System;|
| Sham Comparator: Sham rTMS<br>Sham rTMS is a placebo or inactive form of rTMS for study control and comparison purposes. | Device: Sham rTMS<br>* 10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions of sham rTMS<br>* Other names: Neuronetics 2100 rTMS and James Long Integrated Sham System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gracely Box Intensity Rating Scale | The BIRS is reliable, valid, and sensitive measure that has been used in a number of studies of analgesics and studies of changes of pain intensity over time and was selected as the primary outcome variable. Each scale is a 20 point scale that has clear anchor points. Patients will be classified as responders if they have a 4 point drop or more on the BIRS. In order to be randomized, subjects were to have had a BIRS score of at least 8. Lower scores indicate less pain and higher scores indicate more pain. This measure was administered once a week at Baseline, at the end of weeks 1, 2, and 3 of TMS treatment, and 1 week post-TMS treatment. | Measured weekly | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gracely Box Unpleasantness Scale | The BURS is reliable, valid, and sensitive measure that has been used in a number of studies of analgesics and studies of changes of pain unpleasantness over time. Each scale is a 20 point scale that has clear anchor points. Pain unpleasantness is different from pain intensity in that it assesses the affective and not the somatic aspect of the pain. Lower scores indicate less unpleasantness of pain and higher scores indicate more unpleasantness of pain. This measure was administered at Baseline, after weeks 1, 2, and 3 of TMS treatment, and 1 week post-TMS. | Measured weekly | 
| Hamilton Depression Rating Scale | The research coordinator administered the Hamilton Depression Rating Scale-17 item to assess the level of depression on a weekly basis at baseline, weeks 1, 2, 3 of TMS treatment and 1 week post-TMS treatment. Higher scores indicate a higher level of depression. Scores range from 0-50 and scores greater than 20 generally indicate moderate depression. Scores between 0-7 are considered normal. | Measured weekly | 
| Adverse Events | Adverse events (AEs) were collected by open report of emergent symptoms or illness during the study. This form is filled out during baseline, daily before each TMS session by the trained physician administering the TMS, and at each follow-up visit. | Measured daily | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Fatigue, Chronic Fatigue Syndrome, Chronic Fatigue-Fibromyalgia Syndrome, Depression, Major Depressive Disorder