Transcranial Magnetic Stimulation for Treating Women With Chronic Widespread Pain
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Active rTMS Active rTMS involves administration of real rTMS to the patient. |
Device: 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
Other Names:
|
| Sham Comparator: Sham rTMS Sham rTMS is a placebo or inactive form of rTMS for study control and comparison purposes. |
Device: Sham rTMS
10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions of sham rTMS
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Harborview Medical Center | Seattle | Washington | United States | 98104 |
Sponsors and Collaborators
- University of Washington
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
- Principal Investigator: David H. Avery, MD, University of Washington
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 32656-D
- R21AR053963
- 1R21AR053963-01
- 06-2407-D 01
Study Results
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 Detail | 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. |
| Arm/Group Title | Active rTMS | Sham rTMS |
|---|---|---|
| Arm/Group Description | 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 | Sham rTMS : 10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions of sham rTMS |
| Period Title: Overall Study | ||
| STARTED | 8 | 11 |
| COMPLETED | 7 | 11 |
| NOT COMPLETED | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Active rTMS | Sham rTMS | Total |
|---|---|---|---|
| Arm/Group Description | 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 | Sham rTMS : 10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions of sham rTMS | Total of all reporting groups |
| Overall Participants | 8 | 11 | 19 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
8
100%
|
11
100%
|
19
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
54.86
(7.65)
|
52.09
(10.02)
|
53.17
(9.10)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
8
100%
|
11
100%
|
19
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
8
100%
|
11
100%
|
19
100%
|
Outcome Measures
| Title | Gracely Box Intensity Rating Scale |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Sham rTMS | Active rTMS |
|---|---|---|
| Arm/Group Description | Sham rTMS : 10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions of sham 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 |
| Measure Participants | 11 | 7 |
| Baseline |
13.18
(2.79)
|
14.43
(2.23)
|
| TMS Treatment Week 1 |
10.64
(3.41)
|
13.00
(3.46)
|
| TMS Treatment Week 2 |
10.27
(3.80)
|
11.29
(4.75)
|
| TMS Treatment Week 3 |
8.45
(5.11)
|
10.58
(6.07)
|
| 1 Week Post TMS |
8.60
(5.56)
|
10.50
(5.96)
|
| Title | Gracely Box Unpleasantness Scale |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Sham rTMS | Active rTMS |
|---|---|---|
| Arm/Group Description | Sham rTMS : 10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions of sham 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 |
| Measure Participants | 11 | 7 |
| Baseline |
9.91
(2.77)
|
12.57
(1.72)
|
| TMS Treatment Week 1 |
8.73
(3.32)
|
11.86
(4.38)
|
| TMS Treatment Week 2 |
9.00
(3.85)
|
10.43
(4.61)
|
| TMS Treatment Week 3 |
7.73
(4.13)
|
9.50
(6.50)
|
| 1 Week Post TMS |
7.60
(4.84)
|
9.83
(6.05)
|
| Title | Hamilton Depression Rating Scale |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Sham rTMS | Active rTMS |
|---|---|---|
| Arm/Group Description | Sham rTMS : 10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions of sham 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 |
| Measure Participants | 11 | 7 |
| Baseline |
14.64
(6.34)
|
14.71
(6.55)
|
| TMS Treatment Week 1 |
11.18
(6.60)
|
15.43
(5.38)
|
| TMS Treatment Week 2 |
9.09
(5.13)
|
11.86
(5.96)
|
| TMS Treatment Week 3 |
8.36
(5.01)
|
10.83
(5.78)
|
| 1 Week Post TMS |
7.45
(4.30)
|
8.67
(6.25)
|
| Title | Adverse Events |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Active rTMS | Sham rTMS |
|---|---|---|
| Arm/Group Description | 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 | Sham rTMS : 10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions of sham rTMS |
| Measure Participants | 8 | 11 |
| Number [number of adverse events] |
36
|
35
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Active rTMS | Sham rTMS | ||
| Arm/Group Description | 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 | Sham rTMS : 10 Hz, 4-second trains, 26-second intertrain interval, 75 trains/session, 15 sessions of sham rTMS | ||
All Cause Mortality |
||||
| Active rTMS | Sham rTMS | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Active rTMS | Sham rTMS | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | 0/11 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Active rTMS | Sham rTMS | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/8 (62.5%) | 5/11 (45.5%) | ||
| Cardiac disorders | ||||
| heart palpitations | 0/8 (0%) | 2/11 (18.2%) | ||
| Ear and labyrinth disorders | ||||
| tinnitus | 1/8 (12.5%) | 1/11 (9.1%) | ||
| Eye disorders | ||||
| dry eyes | 0/8 (0%) | 1/11 (9.1%) | ||
| Gastrointestinal disorders | ||||
| nausea | 2/8 (25%) | 1/11 (9.1%) | ||
| abdominal pain | 2/8 (25%) | 1/11 (9.1%) | ||
| diarrhea | 1/8 (12.5%) | 0/11 (0%) | ||
| General disorders | ||||
| dry mouth | 0/8 (0%) | 1/11 (9.1%) | ||
| Infections and infestations | ||||
| sore throat | 1/8 (12.5%) | 1/11 (9.1%) | ||
| coryza | 1/8 (12.5%) | 0/11 (0%) | ||
| cough | 1/8 (12.5%) | 1/11 (9.1%) | ||
| sinus headache | 1/8 (12.5%) | 0/11 (0%) | ||
| flu | 2/8 (25%) | 0/11 (0%) | ||
| viral infection | 1/8 (12.5%) | 0/11 (0%) | ||
| sinus infection | 0/8 (0%) | 1/11 (9.1%) | ||
| sinus congestion | 0/8 (0%) | 1/11 (9.1%) | ||
| sinus drainage | 0/8 (0%) | 1/11 (9.1%) | ||
| Injury, poisoning and procedural complications | ||||
| pain at the site of stimulation | 4/8 (50%) | 3/11 (27.3%) | ||
| tingling sensation in scalp during stimulation | 0/8 (0%) | 1/11 (9.1%) | ||
| lightheadedness after session | 1/8 (12.5%) | 0/11 (0%) | ||
| pain in teeth during stimulation | 0/8 (0%) | 1/11 (9.1%) | ||
| twitching of eye | 0/8 (0%) | 1/11 (9.1%) | ||
| pain in jaw | 0/8 (0%) | 1/11 (9.1%) | ||
| TMJ pain | 1/8 (12.5%) | 0/11 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| increased muscle aches | 2/8 (25%) | 1/11 (9.1%) | ||
| increased fatigue | 1/8 (12.5%) | 1/11 (9.1%) | ||
| tiredness after session | 0/8 (0%) | 1/11 (9.1%) | ||
| pain in thumb | 0/8 (0%) | 1/11 (9.1%) | ||
| pain in shoulder | 0/8 (0%) | 1/11 (9.1%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| sebaceous cyst on thigh | 1/8 (12.5%) | 0/11 (0%) | ||
| Nervous system disorders | ||||
| headache | 5/8 (62.5%) | 5/11 (45.5%) | ||
| insomnia | 2/8 (25%) | 1/11 (9.1%) | ||
| dizziness | 1/8 (12.5%) | 1/11 (9.1%) | ||
| confusion | 0/8 (0%) | 1/11 (9.1%) | ||
| shakiness | 1/8 (12.5%) | 0/11 (0%) | ||
| migraine | 1/8 (12.5%) | 0/11 (0%) | ||
| drowsiness | 0/8 (0%) | 1/11 (9.1%) | ||
| Psychiatric disorders | ||||
| anxiety | 1/8 (12.5%) | 0/11 (0%) | ||
| poor concentration | 1/8 (12.5%) | 0/11 (0%) | ||
| "fuzzy-headed" after TMS | 1/8 (12.5%) | 0/11 (0%) | ||
| feeling more "distant, detached" | 0/8 (0%) | 1/11 (9.1%) | ||
| flat affect | 0/8 (0%) | 1/11 (9.1%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | David H. Avery, MD, Professor |
|---|---|
| Organization | University of Washington |
| Phone | 206-744-4527 |
| averydh@u.washington.edu |
- 32656-D
- R21AR053963
- 1R21AR053963-01
- 06-2407-D 01