Trial Outcomes & Findings for rTMS and Botulinum Toxin in Primary Cervical Dystonia (NCT NCT02542839)
NCT ID: NCT02542839
Last Updated: 2023-12-22
Results Overview
A clinical assessment of dystonia severity will be conducted at each study visit using the TWSTRS. The TWSTRS is a widely accepted composite rating scale for PCD with subscales for clinical severity, functional disability, and associated pain. The total score reported here can range 0-85, where a higher scores represent greater dystonia severity.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
9 participants
Primary outcome timeframe
absolute value at 12 weeks
Results posted on
2023-12-22
Participant Flow
Participant milestones
| Measure |
Real rTMS Stimulation
Repetitive TMS will be delivered over each cerebellar hemisphere, using a NeuroStar TMS therapy system. The coil will be positioned 3 cm lateral to the inion on the line joining the inion and the external auditory meatus. The coil position will be marked on the skin. 900 pulses will be delivered consecutively to each side with a frequency of 1 Hz and at an intensity of 90% of the resting motor threshold (RMT) for a total duration of 15 min for each cerebellar hemisphere. The RMT will be defined as the lowest stimulation intensity required to evoke a 50 μV potential in a target muscle. Constant coil position will be continuously monitored during the experiment. A similar protocol will be observed for the contralateral cerebellum.
NeuroStar TMS therapy: Application of repetitious transcranial magnetic stimulation (TMS) pulses using NeuroStar device to a specific brain target at predefined stimulation parameters.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Craniocervical Dystonia Questionnaire (CDQ-24): All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Cerebellar-brain Inhibition (CBI): All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
|
Sham rTMS Stimulation
Patients will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using sham NeuroStar TMS therapy system coil which produces discharge noise and vibration without stimulating the cerebral cortex. This technique has been suggested to provide more effective blinding compared to other methods use in previous controlled studies. In addition, this group will have the following performed: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) test, Cerebellar-brain Inhibition (CBI) measurement, and Craniocervical Dystonia Questionnaire (CDQ-24) questionnaire to fill out.
Sham NeuroStar TMS therapy: Same procedure as real rTMS without stimulating the cerebral cortex.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Craniocervical Dystonia Questionnaire (CDQ-24): All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Cerebellar-brain Inhibition (CBI): All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
Botulinum toxin injections: All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
4
|
|
Overall Study
COMPLETED
|
5
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
rTMS and Botulinum Toxin in Primary Cervical Dystonia
Baseline characteristics by cohort
| Measure |
Real rTMS Stimulation
n=5 Participants
Repetitive TMS will be delivered over each cerebellar hemisphere, using a NeuroStar TMS therapy system. The coil will be positioned 3 cm lateral to the inion on the line joining the inion and the external auditory meatus. The coil position will be marked on the skin. 900 pulses will be delivered consecutively to each side with a frequency of 1 Hz and at an intensity of 90% of the resting motor threshold (RMT) for a total duration of 15 min for each cerebellar hemisphere.
NeuroStar TMS therapy: Application of repetitious transcranial magnetic stimulation (TMS) pulses using NeuroStar device to a specific brain target at predefined stimulation parameters.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Craniocervical Dystonia Questionnaire (CDQ-24): All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Cerebellar-brain Inhibition (CBI): All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
Botulinum toxin injections: All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
|
Sham rTMS Stimulation
n=4 Participants
Patients will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using sham NeuroStar TMS therapy system coil which produces discharge noise and vibration without stimulating the cerebral cortex. This technique has been suggested to provide more effective blinding compared to other methods use in previous controlled studies. In addition, this group will have the following performed: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) test, Cerebellar-brain Inhibition (CBI) measurement, and Craniocervical Dystonia Questionnaire (CDQ-24) questionnaire to fill out.
Sham NeuroStar TMS therapy: Same procedure as real rTMS without stimulating the cerebral cortex.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Craniocervical Dystonia Questionnaire (CDQ-24): All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Cerebellar-brain Inhibition (CBI): All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
Botulinum toxin injections: All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
|
Total
n=9 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
61 years
STANDARD_DEVIATION 6 • n=5 Participants
|
59 years
STANDARD_DEVIATION 6 • n=7 Participants
|
60 years
STANDARD_DEVIATION 6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
9 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: absolute value at 12 weeksA clinical assessment of dystonia severity will be conducted at each study visit using the TWSTRS. The TWSTRS is a widely accepted composite rating scale for PCD with subscales for clinical severity, functional disability, and associated pain. The total score reported here can range 0-85, where a higher scores represent greater dystonia severity.
Outcome measures
| Measure |
Sham rTMS Stimulation
n=4 Participants
Patients will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using sham NeuroStar TMS therapy system coil which produces discharge noise and vibration without stimulating the cerebral cortex. This technique has been suggested to provide more effective blinding compared to other methods use in previous controlled studies. In addition, this group will have the following performed: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) test, Cerebellar-brain Inhibition (CBI) measurement, and Craniocervical Dystonia Questionnaire (CDQ-24) questionnaire to fill out.
Sham NeuroStar TMS therapy: Same procedure as real rTMS without stimulating the cerebral cortex.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Craniocervical Dystonia Questionnaire (CDQ-24): All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Cerebellar-brain Inhibition (CBI): All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
Botulinum toxin injections: All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
|
Real rTMS Stimulation
n=5 Participants
Repetitive TMS will be delivered over each cerebellar hemisphere, using a NeuroStar TMS therapy system. The coil will be positioned 3 cm lateral to the inion on the line joining the inion and the external auditory meatus. The coil position will be marked on the skin. 900 pulses will be delivered consecutively to each side with a frequency of 1 Hz and at an intensity of 90% of the resting motor threshold (RMT) for a total duration of 15 min for each cerebellar hemisphere.
NeuroStar TMS therapy: Application of repetitious transcranial magnetic stimulation (TMS) pulses using NeuroStar device to a specific brain target at predefined stimulation parameters.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Craniocervical Dystonia Questionnaire (CDQ-24): All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Cerebellar-brain Inhibition (CBI): All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
Botulinum toxin injections: All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
|
|---|---|---|
|
Dystonia Severity as Assessed by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
|
17 scores on a scale
Standard Deviation 8
|
13 scores on a scale
Standard Deviation 6
|
SECONDARY outcome
Timeframe: absolute value at 12 weeksA measure of the cerebellar-brain inhibition(CBI) will be conducted using a TMS device determining the ability of the coil to activate the cerebellum. CBI is calculated by taking the mean of amplitudes of motor-evoked potentials (mV) in response to conditioned stimulation and dividing it by the mean of amplitudes of motor-evoked potentials (mV) in response to unconditioned stimulation (i.e., the control condition). Thus it is a measure of the degree of inhibition due to a conditioning stimulus, where \<1 indicates inhibition, =1 indicates no inhibition, and \>1 indicates not inhibition but excitation. As a ratio of amplitudes, it does not have units.
Outcome measures
| Measure |
Sham rTMS Stimulation
n=4 Participants
Patients will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using sham NeuroStar TMS therapy system coil which produces discharge noise and vibration without stimulating the cerebral cortex. This technique has been suggested to provide more effective blinding compared to other methods use in previous controlled studies. In addition, this group will have the following performed: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) test, Cerebellar-brain Inhibition (CBI) measurement, and Craniocervical Dystonia Questionnaire (CDQ-24) questionnaire to fill out.
Sham NeuroStar TMS therapy: Same procedure as real rTMS without stimulating the cerebral cortex.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Craniocervical Dystonia Questionnaire (CDQ-24): All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Cerebellar-brain Inhibition (CBI): All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
Botulinum toxin injections: All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
|
Real rTMS Stimulation
n=5 Participants
Repetitive TMS will be delivered over each cerebellar hemisphere, using a NeuroStar TMS therapy system. The coil will be positioned 3 cm lateral to the inion on the line joining the inion and the external auditory meatus. The coil position will be marked on the skin. 900 pulses will be delivered consecutively to each side with a frequency of 1 Hz and at an intensity of 90% of the resting motor threshold (RMT) for a total duration of 15 min for each cerebellar hemisphere.
NeuroStar TMS therapy: Application of repetitious transcranial magnetic stimulation (TMS) pulses using NeuroStar device to a specific brain target at predefined stimulation parameters.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Craniocervical Dystonia Questionnaire (CDQ-24): All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Cerebellar-brain Inhibition (CBI): All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
Botulinum toxin injections: All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
|
|---|---|---|
|
TMS Measure Referred to as Cerebellar Inhibition (CBI)
|
0.9 ratio
Standard Deviation 0.3
|
0.7 ratio
Standard Deviation 0.2
|
SECONDARY outcome
Timeframe: absolute value at 12 WeeksThe Craniocervical Dystonia Questionnaire (CDQ-24) is a patient-rated health related quality of life (HR-QoL) measure for craniocervical dystonia. It is composed of 24 items, forming 5 subscales: stigma, emotional well-being, pain, activities of daily living, and social/ family life. Items are rated on a 5-point scale. Each item consists of five statements representing increasing severity of impairment, scored from 0 to 4. Subjects will be instructed to indicate how they have felt during the past two weeks because of dystonia by selecting one of the five statements for each item. The total score reported here can range from 0-96, with a higher score indicating a greater impact of dystonia on quality of life.
Outcome measures
| Measure |
Sham rTMS Stimulation
n=4 Participants
Patients will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using sham NeuroStar TMS therapy system coil which produces discharge noise and vibration without stimulating the cerebral cortex. This technique has been suggested to provide more effective blinding compared to other methods use in previous controlled studies. In addition, this group will have the following performed: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) test, Cerebellar-brain Inhibition (CBI) measurement, and Craniocervical Dystonia Questionnaire (CDQ-24) questionnaire to fill out.
Sham NeuroStar TMS therapy: Same procedure as real rTMS without stimulating the cerebral cortex.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Craniocervical Dystonia Questionnaire (CDQ-24): All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Cerebellar-brain Inhibition (CBI): All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
Botulinum toxin injections: All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
|
Real rTMS Stimulation
n=5 Participants
Repetitive TMS will be delivered over each cerebellar hemisphere, using a NeuroStar TMS therapy system. The coil will be positioned 3 cm lateral to the inion on the line joining the inion and the external auditory meatus. The coil position will be marked on the skin. 900 pulses will be delivered consecutively to each side with a frequency of 1 Hz and at an intensity of 90% of the resting motor threshold (RMT) for a total duration of 15 min for each cerebellar hemisphere.
NeuroStar TMS therapy: Application of repetitious transcranial magnetic stimulation (TMS) pulses using NeuroStar device to a specific brain target at predefined stimulation parameters.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Craniocervical Dystonia Questionnaire (CDQ-24): All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Cerebellar-brain Inhibition (CBI): All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
Botulinum toxin injections: All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
|
|---|---|---|
|
Craniocervical Dystonia Questionnaire
|
18 score on a scale
Standard Deviation 6
|
16 score on a scale
Standard Deviation 4
|
Adverse Events
Real rTMS Stimulation
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Sham rTMS Stimulation
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Real rTMS Stimulation
n=5 participants at risk
Repetitive TMS will be delivered over each cerebellar hemisphere, using a NeuroStar TMS therapy system. The coil will be positioned 3 cm lateral to the inion on the line joining the inion and the external auditory meatus. The coil position will be marked on the skin. 900 pulses will be delivered consecutively to each side with a frequency of 1 Hz and at an intensity of 90% of the resting motor threshold (RMT) for a total duration of 15 min for each cerebellar hemisphere.
NeuroStar TMS therapy: Application of repetitious transcranial magnetic stimulation (TMS) pulses using NeuroStar device to a specific brain target at predefined stimulation parameters.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Craniocervical Dystonia Questionnaire (CDQ-24): All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Cerebellar-brain Inhibition (CBI): All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
Botulinum toxin injections: All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
|
Sham rTMS Stimulation
n=4 participants at risk
Patients will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using sham NeuroStar TMS therapy system coil which produces discharge noise and vibration without stimulating the cerebral cortex.
Sham NeuroStar TMS therapy: Same procedure as real rTMS without stimulating the cerebral cortex.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.
Craniocervical Dystonia Questionnaire (CDQ-24): All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.
Cerebellar-brain Inhibition (CBI): All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.
Botulinum toxin injections: All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care
|
|---|---|---|
|
Nervous system disorders
headaches
|
40.0%
2/5 • Number of events 2 • 12 weeks
|
25.0%
1/4 • Number of events 1 • 12 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place