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| ID | Type | Description | Link |
|---|---|---|---|
| OCR40846 | Other Identifier | UF OnCore |
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| Name | Class |
|---|---|
| Dystonia Medical Research Foundation | OTHER |
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We applied 16 sessions of rTMS over 4 consecutive days for adult patients suffering from cervical dystonia who received botulinum toxin (BoNT) injections on a regular basis. The TMS protocol took place 9 weeks following their last BoNT injection. The primary outcome measure was improvement in cervical dystonia as measured by the TWSTRS scale. The secondary outcome measures included mood, cognition, and gait measures.
This was a crossover study design in which patients were randomized to active or sham stimulation during session 1 (S1) and then crossed over to the condition they were not randomized to at first during session 2 (S1). Patients who were receiving BoNT injections for cervical dystonia on a regular basis but only noted benefit from BoNT for 9 weeks or less were eligible to participate. The total study protocol took place over 24 weeks. During week 1, patients had their regularly scheduled botox injections. During week 9, patients underwent either active or sham rTMS, as detailed below. They had outcome measures obtained at week 9 (S1:T0; baseline/pre-TMS), week 10 (S1:T1; post-TMS), and week 12 (S1:T2; 2 weeks post-TMS). At week 12, they underwent their regularly scheduled BoNT injections. During week 21, patients underwent either active or sham rTMS, whichever condition they were not randomized into during the first session. They then had outcome measures obtained at week 21 (S2:T0; baseline/pre-TMS), week 22 (S2:T1; post-TMS), and week 24 (S2:T2; 2 weeks post-TMS).
The neurostimulation protocol was as follows: The dPMC target was defined as 1 cm medial and 2 cm anterior to the site of RMT acquisition. The rTMS protocol was as follows: each session consisted of 1-Hz rTMS over the dPMC for 30 minutes (1800 pulses) at 90% of the RMT. Patients received 4 sessions per day for 4 consecutive days with a 10-minute break between each session. The daily duration of the rTMS protocol, including breaks, lasted approximately 160 minutes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active rTMS | Active Comparator | Active rTMS will use a figure of eight TMS coil that will deliver real neurostimulation pulses to the patients. |
|
| Sham rTMS | Sham Comparator | Sham rTMS will use a sham figure of eight TMS coil that sounds and looks like a real rTMS coil, except no neurostimulation is being delivered to the patient. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rTMS | Device | repetitive transcranial magnetic stimulation is a painless, noninvasive form of neurostimulation. This study uses an accelerated protocol in which the neurostimulation pulses are delivered in 4 sessions per day over 4 consecutive days (16 total sessions). Active or sham rTMS will be provided at 9 weeks following botox injections. |
| Measure | Description | Time Frame |
|---|---|---|
| Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | This is an objective scale evaluating patients on a variety of features including maximal excursion, duration, effects of sensory trick, shoulder elevation, range of motion, and time. Scores range from 0 to 85 where a higher score indicates more severity. | Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24) |
| Measure | Description | Time Frame |
|---|---|---|
| Beck Depression Inventory (BDI) | This is a 21-question survey evaluating depression in patients on a 0 to 3 scale, with a minimum score of 0 and maximum score 63, and higher score indicating a higher level of depression. | Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jun Yu, MD, MS | University of Florida | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida Health Norman Fixel Institute for Neurological Diseases | Gainesville | Florida | 32608 | United States |
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At 9 weeks after their regularly scheduled botulinum toxin injection visits, the participants were randomly assigned to receive either active rTMS first or sham first.
This was a prospective, randomized, double-blind, crossover study. Five participants were recruited at the University of Florida Norman Fixel Institute for Neurological Diseases. Recruitment occurred between January and February 2022.
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| ID | Title | Description |
|---|---|---|
| FG000 | Active rTMS First | The active repetitive transcranial magnetic stimulation (rTMS) was provided at 9 weeks following the botulinum toxin injection. First, a clinical therapeutic NeuroStar TMS coil (Neuronetics, Malvern, PA) was used to determine the resting motor threshold (RMT), defined as the lowest stimulation intensity required to evoke a muscle twitch in a target muscle (first dorsal interosseus) for 5/10 pulses. The dPMC target was defined as 1 cm medial and 2 cm anterior to the site of RMT acquisition, consistent with how this target has been defined in the literature previously. Then, the clinical therapeutic TMS coil was switched to the active NeuroStar TMS coil. The rTMS protocol was as follows: each session consisted of 1-Hz rTMS over the dPMC for 30 minutes (1800 pulses) at 90% of the RMT. This study used an accelerated protocol: patients received 4 sessions per day for 4 consecutive days with a 10-minute break between each session. The daily duration of the rTMS protocol, including breaks, lasted approximately 160 minutes. |
| FG001 | Sham rTMS First | The sham rTMS was provided at 9 weeks following the botulinum toxin injection. First, the participants underwent the same procedure for identifying the target location and RMT as was used in patients receiving active rTMS. Then, the simulated rTMS was administered using a NeuroStar sham coil, which looked the same as the active stimulation coil and produced discharge noise and vibration without stimulating the cerebral cortex. This technique has been suggested to provide the most effective blinding compared to other methods used in randomized, controlled rTMS studies. The physician who set up the active and sham coils played no role in outcome measure assessments in order to maintain blinding. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (4 Days) |
| |||||||||||||
| Washout (12 Weeks) |
| |||||||||||||
| Second Intervention (4 Days) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Active rTMS First | The active repetitive transcranial magnetic stimulation (rTMS) was provided at 9 weeks following the botulinum toxin injection. First, a clinical therapeutic NeuroStar TMS coil (Neuronetics, Malvern, PA) was used to determine the resting motor threshold (RMT), defined as the lowest stimulation intensity required to evoke a muscle twitch in a target muscle (first dorsal interosseus) for 5/10 pulses. The dPMC target was defined as 1 cm medial and 2 cm anterior to the site of RMT acquisition, consistent with how this target has been defined in the literature previously. Then, the clinical therapeutic TMS coil was switched to the active NeuroStar TMS coil. The rTMS protocol was as follows: each session consisted of 1-Hz rTMS over the dPMC for 30 minutes (1800 pulses) at 90% of the RMT. This study used an accelerated protocol: patients received 4 sessions per day for 4 consecutive days with a 10-minute break between each session. The daily duration of the rTMS protocol, including breaks, lasted approximately 160 minutes. |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | This is an objective scale evaluating patients on a variety of features including maximal excursion, duration, effects of sensory trick, shoulder elevation, range of motion, and time. Scores range from 0 to 85 where a higher score indicates more severity. | Posted | Mean | Standard Deviation | score on a scale | Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24) |
|
24 weeks
All-Cause Mortality Serious Adverse Events Other Adverse Events
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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 | The active or sham repetitive transcranial magnetic stimulation (rTMS) was provided at 9 weeks following the botulinum toxin injection. First, a clinical therapeutic NeuroStar TMS coil (Neuronetics, Malvern, PA) was used to determine the resting motor threshold (RMT), defined as the lowest stimulation intensity required to evoke a muscle twitch in a target muscle (first dorsal interosseus) for 5/10 pulses. The dPMC target was defined as 1 cm medial and 2 cm anterior to the site of RMT acquisition, consistent with how this target has been defined in the literature previously. Then, the clinical therapeutic TMS coil was switched to the active NeuroStar TMS coil. The rTMS protocol was as follows: each session consisted of 1-Hz rTMS over the dPMC for 30 minutes (1800 pulses) at 90% of the RMT. This study used an accelerated protocol: patients received 4 sessions per day for 4 consecutive days with a 10-minute break between each session. The daily duration of the rTMS protocol, including breaks, lasted approximately 160 minutes. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jun Yu | University of Florida Norman Fixel Institute for Neurological Diseases | 352-294-5400 | jun.yu@neurology.ufl.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 17, 2022 | Dec 8, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 21, 2024 | Jul 20, 2024 | SAP_003.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 6, 2022 | Oct 24, 2022 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D014103 | Torticollis |
| ID | Term |
|---|---|
| D004421 | Dystonia |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
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Patients were randomized to one of two conditions during session 1: active or sham rTMS. During session 2, patients underwent whichever condition they did not undergo in session 1.
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A sham coil was used for sham rTMS. Both conditions underwent the exact same study procedures except the sham coil did not deliver pulses; it did still deliver a sound and tapping sensation meant to mimic the real rTMS coil, but no real stimulation was provided in this condition. Patients and outcomes assessors were not made aware of the condition that the participant was partaking in.
|
|
| Trail-Making Test: Part A | Patients are instructed to connect circles in ascending numerical order and are scored on how quickly they are able to complete the task. A longer amount of time indicates more severe cognitive impairment (in general, more than 78 seconds to complete Part A is considered impaired). | Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24) |
| Trail-Making Test: Part B | Patients are instructed to connect circles in ascending numerical order and are scored on how quickly they are able to complete the task. A longer amount of time indicates more severe cognitive impairment (in general, more than 273 seconds to complete Part B is considered impaired). | Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24) |
| Wisconsin Card Sorting Task (WCST) - %Total Errors | The Wisconsin Card Sorting Test is a test of rule-learning and conceptual flexibility. The participant is required to learn to sort a series of cards according to one of three principles (color, form or number) based on response feedback. This measure is computed by calculating the ration of total errors to trials administered and multiplied by 100. | Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24) |
| Wisconsin Card Sorting Task (WCST) - %Perseverative Errors | The Wisconsin Card Sorting Test is a test of rule-learning and conceptual flexibility. The participant is required to learn to sort a series of cards according to one of three principles (color, form or number) based on response feedback. This measure reflects the "density" of perseverative errors in relation to the overall test performance. It is computed by calculating the ration of total errors to trials administered and multiplied by 100. | Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24) |
| NOT COMPLETED |
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| NOT COMPLETED |
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| BG001 | Sham rTMS First | The sham rTMS was provided at 9 weeks following the botulinum toxin injection. First, the participants underwent the same procedure for identifying the target location and RMT as was used in patients receiving active rTMS. Then, the simulated rTMS was administered using a NeuroStar sham coil, which looked the same as the active stimulation coil and produced discharge noise and vibration without stimulating the cerebral cortex. This technique has been suggested to provide the most effective blinding compared to other methods used in randomized, controlled rTMS studies. The physician who set up the active and sham coils played no role in outcome measure assessments in order to maintain blinding. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Duration since dystonia onset | Mean | Full Range | years |
|
| Sensory trick | Count of Participants | Participants |
|
| Other dystonic features | Count of Participants | Participants |
|
| Family history | Count of Participants | Participants |
|
| Neurotoxin | Count of Participants | Participants |
|
| Dosage | Out of the 5 participants, 3 were receiving onabotulinumtoxinA injection, 1 incobotulinumtoxinA injection, and 1 rimabotulinumtoxinB injection. | Mean | Full Range | units |
|
| OG001 | Sham rTMS | Participants who received sham repetitive transcranial magnetic stimulation (rTMS) during either the first intervention or the second intervention period. First, the participants underwent the same procedure for identifying the target location and RMT as was used in patients receiving active rTMS. Then, the simulated rTMS was administered using a NeuroStar sham coil, which looked the same as the active stimulation coil and produced discharge noise and vibration without stimulating the cerebral cortex. This technique has been suggested to provide the most effective blinding compared to other methods used in randomized, controlled rTMS studies. The physician who set up the active and sham coils played no role in outcome measure assessments in order to maintain blinding. |
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| Secondary | Beck Depression Inventory (BDI) | This is a 21-question survey evaluating depression in patients on a 0 to 3 scale, with a minimum score of 0 and maximum score 63, and higher score indicating a higher level of depression. | Posted | Mean | Standard Deviation | score on a scale | Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24) |
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| Secondary | Trail-Making Test: Part A | Patients are instructed to connect circles in ascending numerical order and are scored on how quickly they are able to complete the task. A longer amount of time indicates more severe cognitive impairment (in general, more than 78 seconds to complete Part A is considered impaired). | Posted | Mean | Standard Deviation | seconds | Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24) |
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| Secondary | Trail-Making Test: Part B | Patients are instructed to connect circles in ascending numerical order and are scored on how quickly they are able to complete the task. A longer amount of time indicates more severe cognitive impairment (in general, more than 273 seconds to complete Part B is considered impaired). | Posted | Mean | Standard Deviation | seconds | Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24) |
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| Secondary | Wisconsin Card Sorting Task (WCST) - %Total Errors | The Wisconsin Card Sorting Test is a test of rule-learning and conceptual flexibility. The participant is required to learn to sort a series of cards according to one of three principles (color, form or number) based on response feedback. This measure is computed by calculating the ration of total errors to trials administered and multiplied by 100. | Posted | Mean | Standard Deviation | percentage | Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24) |
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| Secondary | Wisconsin Card Sorting Task (WCST) - %Perseverative Errors | The Wisconsin Card Sorting Test is a test of rule-learning and conceptual flexibility. The participant is required to learn to sort a series of cards according to one of three principles (color, form or number) based on response feedback. This measure reflects the "density" of perseverative errors in relation to the overall test performance. It is computed by calculating the ration of total errors to trials administered and multiplied by 100. | Posted | Mean | Standard Deviation | percentage | Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24) |
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|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 2 |
| 5 |
| EG001 | Sham rTMS | The active or sham rTMS was provided at 9 weeks following the botulinum toxin injection. First, the participants underwent the same procedure for identifying the target location and RMT as was used in patients receiving active rTMS. Then, the simulated rTMS was administered using a NeuroStar sham coil, which looked the same as the active stimulation coil and produced discharge noise and vibration without stimulating the cerebral cortex. This technique has been suggested to provide the most effective blinding compared to other methods used in randomized, controlled rTMS studies. The physician who set up the active and sham coils played no role in outcome measure assessments in order to maintain blinding. | 0 | 5 | 0 | 5 | 2 | 5 |
| Neck discomfort | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| RimabotulinumtoxinB |
|
| 2 weeks after rTMS |
|
| 2 weeks after rTMS |
|
| 2 weeks after rTMS |
|
| 2 weeks after rTMS |
|
| 2 weeks after rTMS |
|