rTMS and Rehabilitation for Individuals With CRPS Type 1

Study Overview
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Brief Summary
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Subjects with complex regional pain syndrome (CRPS) Type 1 will be randomized to receive repeated transcranial magnetic stimulation (rTMS) followed by rehabilitation or sham rTMS followed by rehabilitation. Treatment will last for 4 weeks, with the first week including 4 rTMS treatments and 2 rehabilitation treatments. Subsequent weeks will include 2 rTMS treatments followed by 2 rehabilitation treatments. Outcome measures will include pain ratings, PROMIS questionnaires, global rating of change, and grip strength or 1 repetition maximum leg press.

Detailed Description
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Subjects will be randomized to receive either real or sham rTMS, combined with rehabilitation. Subjects will attend 10 sessions over 4 weeks. rTMS will be delivered at 10Hz using an intensity of 80% of the motor threshold. Pulse trains will be delivered for 10 seconds, with a 30-second rest for 20 repetitions. This will result in a total of 2,000 pulses of magnetic stimulation and will take approximately 20 minutes. There will be 10 rTMS sessions over the 4 weeks. Sham rTMS will be delivered using the same method as rTMS, but a sham coil, that does not deliver magnetic stimulation, will be used. Rehabilitation will include graded motor imagery, education, and graded functional activity. There will be 8 rehabilitation sessions over 4 weeks. Outcomes will include questionnaires asking about pain and function, and either grip strength or leg press strength measurements.

Official Title
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Repeated Transcranial Magnetic Stimulation and Rehabilitation for Individuals With Complex Regional Pain Syndrome Type 1

Conditions
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Complex Regional Pain Syndrome Type I

Intervention / Treatment
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* Device: Repeated Transcranial Magnetic Stimulation
* Device: Sham Repeated Transcranial Magnetic Stimulation
* Other: Rehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Upper or lower extremity CRPS Type 1 (also called RSD-Reflex Sympathetic Dystrophy) of at least 6 months. Pain rating on NPRS of at least 4/10 No initiation of a new intervention (i.e., medication, rehab, injections) in the previous 2 months. No plan to initiate a new intervention during the study treatment timeframe (4 weeks). Exclusion Criteria: A history of seizures or epilepsy Intracranial metallic devices Pacemaker Intrathecal infusion pumps Brain or spinal cord stimulators with epidural electrodes Other ferromagnetic metallic intracranial implants Apparent mental or psychiatric disorder that prevents adequate informed consent Current pregnancy Non-English speaking

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: rTMS and Rehabilitation<br>Subjects in this arm will get rTMS to the contralateral motor cortex and best practice rehabilitation. | Device: Repeated Transcranial Magnetic Stimulation<br>* rTMS will be delivered using a commercially available magnetic stimulator (Rapid2, Magstim Inc., Eden Prairie, MN) with a figure-of-8 Air Film coil at 10 Hz. Coil orientation will be optimized for stimulation of the abductor pollicis brevis. Stimulation targeting will be identified using motor-evoked potentials (MEP) of the first dorsal interossei that will be monitored using electromyography (EMG) (Motion Lab Systems Inc., Baton Rouge, LA). The motor threshold (MT) of the muscle will then be identified by systematically adjusting the pulse intensity. The MT will be considered the lowest stimulation intensity at which 5 out of 10 MEPs have a peak-to-peak amplitude of at least 50 microvolts. rTMS will be performed at the identified optimal location at 10Hz using an intensity that is 80% of the MT. Pulse trains will be delivered for 10 seconds, with a 30-second rest for 20 repetitions.<br>* Other names: rTMS;Other: Rehabilitation<br>* Rehabilitation will consist of education, value-based goal setting, Graded Motor Imagery (GMI) (3 components described below), and graded activity. Subjects will complete activities at treatment sessions and be asked to perform certain treatment activities at home. Week 1: Pain education, functional value-based goal setting, laterality training (first component of GMI), one task for graded activity (task-based on patient goals) Week 2: Continue week 1 activity, add graded motor imagery (second component of GMI), progress 1st graded activity, and initiate 2nd graded activity exercise. Week 3- Mirror therapy (third component of GMI), assess knowledge and update education as needed, progress graded activity 1 and 2, and add 3rd graded activity if appropriate based on patient goals. Week 4- Continue with week 3 activities. Discuss experience with meditation and progress graded activity as tolerated<br>|
| Sham Comparator: Sham rTMS and Rehabilitation<br>Subjects in this arm will get sham rTMS to the contralateral motor cortex and best practice rehabilitation. | Device: Sham Repeated Transcranial Magnetic Stimulation<br>* Sham rTMS will be performed using the same methods as the active group, but a sham Air Film coil (Magstim Inc., Eden Prairie, MN) will be used. This coil looks and sounds like the active coil, but it does not deliver magnetic pulses.<br>* Other names: SrTMS;Other: Rehabilitation<br>* Rehabilitation will consist of education, value-based goal setting, Graded Motor Imagery (GMI) (3 components described below), and graded activity. Subjects will complete activities at treatment sessions and be asked to perform certain treatment activities at home. Week 1: Pain education, functional value-based goal setting, laterality training (first component of GMI), one task for graded activity (task-based on patient goals) Week 2: Continue week 1 activity, add graded motor imagery (second component of GMI), progress 1st graded activity, and initiate 2nd graded activity exercise. Week 3- Mirror therapy (third component of GMI), assess knowledge and update education as needed, progress graded activity 1 and 2, and add 3rd graded activity if appropriate based on patient goals. Week 4- Continue with week 3 activities. Discuss experience with meditation and progress graded activity as tolerated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Pain Rating Scale (NPRS) Weekly Average | Subjects will be asked to rate their weekly average pain on a scale from 0-10 (0 indicating no pain and 10 indicating worse possible pain). | Sessions 1 (week 1), 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4). Surveys will also be sent at 4 weeks, 3 months, 6 months, and 1 year after last session. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Pain Rating Scale (NPRS) worse/least pain over 24 hours | Subjects will be asked to rate their highest pain level and lowest pain level over a 24-hour period. (0 indicating no pain and 10 indicating worse possible pain). | Sessions 1 (week 1), 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4). Surveys will also be sent at 4 weeks, 3 months, 6 months, and 1 year after last session | 
| Patient-Reported Outcomes Measurement Information Systems (PROMIS). | NIH developed computer adaptive tools measuring pain interference, pain behavior, physical functioning, social roles, fatigue, depression, anxiety, and anger. Scores are reported based on T-scores with a mean population score of 50 and a standard deviation of 10. Scores generally range from 20-80. For symptom scales (i.e. pain interference), higher scores indicate worse symptoms, and for function scales (i.e. social roles), higher scores indicate better function. | Sessions 1 (week 1), 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4). Surveys will also be sent at 4 weeks, 3 months, 6 months, and 1 year after last session | 
| Global Rating of Change (GROC) | Subjects will be asked to rate the change of their symptoms from 7(a great deal better) to -7 (a great deal worse) with 0 being no different. | Sessions 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4). Surveys will also be sent at 4 weeks, 3 months, 6 months, and 1 year after last session | 
| Global Rating of Change Impact (GROCi) | Subjects will be asked to rate the impact of the change from 7(a great deal better) to -7 (a great deal worse) with 0 being no different. | Sessions 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4) Surveys will also be sent at 4 weeks, 3 months, 6 months, and 1 year after last session | 
| Patient Acceptable Symptom State (PASS) | Patients are asked if their current state of symptoms is acceptable, yes/no | Sessions 1 (week 1), 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4). Surveys will also be sent at 4 weeks, 3 months, 6 months, and 1 year after last session. | 
| Grip Strength or 1 Rep Leg Press | Subjects with upper extremity involvement will have grip strength measured using a dynamometer. Subjects with lower extremity involvement will be tested with single leg 1 rep max leg press. | Sessions 1 (week 1), 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4). |