Chronic Pain, Depression, Fibromyalgia
Conditions
Keywords
Pain, Fatigue, Chronic Fatigue Syndrome, Chronic Fatigue-Fibromyalgia Syndrome, Depression, Major Depressive Disorder
Brief summary
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
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.
Interventions
DEVICErTMS
10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions at 120% motor threshold rTMS to left dorsolateral prefrontal cortex
DEVICESham rTMS
10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions of sham rTMS
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gracely Box Intensity Rating Scale | Measured weekly | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gracely Box Unpleasantness Scale | Measured weekly | 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. |
| Hamilton Depression Rating Scale | Measured weekly | 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. |
| Adverse Events | Measured daily | 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. |
Countries
United States
Participant flow
Recruitment details
The study was conducted between January 2008 and November 2010. Subjects were recruited from advertisements, referrals, and from a University of Washington clinic that specializes in Fibromyalgia.
Pre-assignment details
493 subjects were screened over the phone. 31 subjects came into the clinic for an initial screening visit. Subjects were allowed to maintain stable doses of medication and psychotherapy. 12 of the screened subjects did not meet criteria for randomization. The remaining 19 were randomized, and 18 completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Active rTMS rTMS : 10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions at 120% motor threshold rTMS to left dorsolateral prefrontal cortex | 8 |
| Sham rTMS Sham rTMS : 10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions of sham rTMS | 11 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 |
Baseline characteristics
| Characteristic | Sham rTMS | Active rTMS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 8 Participants | 19 Participants |
| Age Continuous | 52.09 years STANDARD_DEVIATION 10.02 | 54.86 years STANDARD_DEVIATION 7.65 | 53.17 years STANDARD_DEVIATION 9.1 |
| Region of Enrollment United States | 11 participants | 8 participants | 19 participants |
| Sex: Female, Male Female | 11 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 8 | 5 / 11 |
| serious Total, serious adverse events | 0 / 8 | 0 / 11 |
Outcome results
Primary
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.
Time frame: Measured weekly
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham rTMS | Gracely Box Intensity Rating Scale | TMS Treatment Week 1 | 10.64 units on a scale | Standard Deviation 3.41 |
| Sham rTMS | Gracely Box Intensity Rating Scale | TMS Treatment Week 3 | 8.45 units on a scale | Standard Deviation 5.11 |
| Sham rTMS | Gracely Box Intensity Rating Scale | TMS Treatment Week 2 | 10.27 units on a scale | Standard Deviation 3.8 |
| Sham rTMS | Gracely Box Intensity Rating Scale | 1 Week Post TMS | 8.60 units on a scale | Standard Deviation 5.56 |
| Sham rTMS | Gracely Box Intensity Rating Scale | Baseline | 13.18 units on a scale | Standard Deviation 2.79 |
| Active rTMS | Gracely Box Intensity Rating Scale | 1 Week Post TMS | 10.50 units on a scale | Standard Deviation 5.96 |
| Active rTMS | Gracely Box Intensity Rating Scale | Baseline | 14.43 units on a scale | Standard Deviation 2.23 |
| Active rTMS | Gracely Box Intensity Rating Scale | TMS Treatment Week 1 | 13.00 units on a scale | Standard Deviation 3.46 |
| Active rTMS | Gracely Box Intensity Rating Scale | TMS Treatment Week 2 | 11.29 units on a scale | Standard Deviation 4.75 |
| Active rTMS | Gracely Box Intensity Rating Scale | TMS Treatment Week 3 | 10.58 units on a scale | Standard Deviation 6.07 |
Secondary
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.
Time frame: Measured daily
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sham rTMS | Adverse Events | 36 number of adverse events |
| Active rTMS | Adverse Events | 35 number of adverse events |
Secondary
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.
Time frame: Measured weekly
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham rTMS | Gracely Box Unpleasantness Scale | TMS Treatment Week 1 | 8.73 units on a scale | Standard Deviation 3.32 |
| Sham rTMS | Gracely Box Unpleasantness Scale | TMS Treatment Week 3 | 7.73 units on a scale | Standard Deviation 4.13 |
| Sham rTMS | Gracely Box Unpleasantness Scale | TMS Treatment Week 2 | 9.00 units on a scale | Standard Deviation 3.85 |
| Sham rTMS | Gracely Box Unpleasantness Scale | 1 Week Post TMS | 7.60 units on a scale | Standard Deviation 4.84 |
| Sham rTMS | Gracely Box Unpleasantness Scale | Baseline | 9.91 units on a scale | Standard Deviation 2.77 |
| Active rTMS | Gracely Box Unpleasantness Scale | 1 Week Post TMS | 9.83 units on a scale | Standard Deviation 6.05 |
| Active rTMS | Gracely Box Unpleasantness Scale | Baseline | 12.57 units on a scale | Standard Deviation 1.72 |
| Active rTMS | Gracely Box Unpleasantness Scale | TMS Treatment Week 1 | 11.86 units on a scale | Standard Deviation 4.38 |
| Active rTMS | Gracely Box Unpleasantness Scale | TMS Treatment Week 2 | 10.43 units on a scale | Standard Deviation 4.61 |
| Active rTMS | Gracely Box Unpleasantness Scale | TMS Treatment Week 3 | 9.50 units on a scale | Standard Deviation 6.5 |
Secondary
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.
Time frame: Measured weekly
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham rTMS | Hamilton Depression Rating Scale | TMS Treatment Week 1 | 11.18 units on a scale | Standard Deviation 6.6 |
| Sham rTMS | Hamilton Depression Rating Scale | TMS Treatment Week 3 | 8.36 units on a scale | Standard Deviation 5.01 |
| Sham rTMS | Hamilton Depression Rating Scale | TMS Treatment Week 2 | 9.09 units on a scale | Standard Deviation 5.13 |
| Sham rTMS | Hamilton Depression Rating Scale | 1 Week Post TMS | 7.45 units on a scale | Standard Deviation 4.3 |
| Sham rTMS | Hamilton Depression Rating Scale | Baseline | 14.64 units on a scale | Standard Deviation 6.34 |
| Active rTMS | Hamilton Depression Rating Scale | 1 Week Post TMS | 8.67 units on a scale | Standard Deviation 6.25 |
| Active rTMS | Hamilton Depression Rating Scale | Baseline | 14.71 units on a scale | Standard Deviation 6.55 |
| Active rTMS | Hamilton Depression Rating Scale | TMS Treatment Week 1 | 15.43 units on a scale | Standard Deviation 5.38 |
| Active rTMS | Hamilton Depression Rating Scale | TMS Treatment Week 2 | 11.86 units on a scale | Standard Deviation 5.96 |
| Active rTMS | Hamilton Depression Rating Scale | TMS Treatment Week 3 | 10.83 units on a scale | Standard Deviation 5.78 |