Cervical Dystonia, Spasmodic Torticollis
Conditions
Keywords
cervical dystonia, torticollis, rTMS
Brief summary
The overall objective of this application is to therapeutically target the dysfunctional premotor-motor interaction in dystonia-and to provide a focused treatment of specific anatomical networks in order to reduce side effects and to improve symptom control over conventional therapies.
Detailed description
We propose using repetitive transcranial magnetic stimulation (rTMS) over distinct premotor areas in patients with cervical dystonia (CD) with the goal of improving symptoms and reducing unwanted side effects. The knowledge gained in this proposed research will identify a specific premotor area to be targeted with rTMS that is expected to result in a novel intervention that could enhance or replace current treatments for CD. rTMS could be included as an adjunct treatment to botulinum toxin that could sustain treatment effect and decrease the frequency of re-injection, potentially resulting in cost savings without a decrease in symptom control. In addition to medical cost reduction, improved quality of life could be expected with the successful development of therapies that extend dystonia symptom control. rTMs has been FDA-approved for the treatment of depression and our proposal uses an even lower stimulation rate, suggesting continued use within clearly safe parameters. Successful completion of this research could lead to rapid adoption of this therapeutic modality. We will test the hypothesis that rTMS of a distinct premotor site will provide more effective treatment of CD than non-specific activation of the entire premotor region. This will be done by performing a randomized, observer-blinded exploratory pilot study to determine the optimal site of rTMS over various sites of the premotor and motor cortex to improve the symptoms of cervical dystonia. Completion of this aim should lead to development of targeted TMS therapy for CD.
Interventions
DEVICErTMS
Sponsors
Dystonia Coalition
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
University Health Network, Toronto
University of New Mexico
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of idiopathic cervical dystonia * Age 18 years or older * Normal findings in the medical history, physical and neurological examination, except for dystonia * Last treatment with botulinum toxin more than two months ago
Exclusion criteria
* History of seizure disorder * Pregnancy- a pregnancy test will be performed for women of childbearing potential * History of any other neurological disorders or conditions requiring the use of anti-depressants that are known to increase seizure threshold, neuroleptic medication, anticholinergic drugs and muscle relaxants * History of neuroleptic medications/ prior use of neuroleptics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | Change from baseline pre-intervention TWSTRS score to post-intervention within 1 hour of treatment | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was used to assess severity of disease. The score for this section ranges from 0 (absence of severity) to 35 (maximum severity). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dorsal Premotor-motor Inhibition (dPMI) | Change from baseline dPMI to post-intervention within 1 hour of treatment | — |
| Composite Measure of Patient Rating of Symptoms and Tolerability | Assessment completed immediately after rTMS treatment session | This measure will confirm the intervention tolerability by the patient. He/she scored the tolerability from 0-10, 0 being completely tolerable and 10 completely intolerable. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subject 1 Received rTMS intervention in the following order, each at 0.2Hz for 15 minutes:
Primary Motor Cortex Supplemental Motor Area Sham Dorsal Premotor Cortex Anterior Cingulate Cortex | 1 |
| Subject 2 Received rTMS intervention in the following order, each at 0.2Hz for 15 minutes:
Anterior Cingulate Cortex Primary Motor Cortex Dorsal Premotor Cortex Sham Supplemental Motor Area | 1 |
| Subject 3 Received rTMS intervention in the following order, each at 0.2Hz for 15 minutes:
Dorsal Premotor Cortex Supplemental Motor Area Sham Primary Motor Cortex Anterior Cingulate Cortex | 1 |
| Subject 4 Received rTMS intervention in the following order, each at 0.2Hz for 15 minutes:
Supplemental Motor Area Sham Anterior Cingulate Cortex Primary Motor Cortex Dorsal Premotor Cortex | 1 |
| Subject 5 Received rTMS intervention in the following order, each at 0.2Hz for 15 minutes:
Sham Dorsal Premotor Cortex Primary Motor Cortex Supplemental Motor Area Anterior Cingulate Cortex | 1 |
| Subject 6 Received rTMS intervention in the following order, each at 0.2Hz for 15 minutes:
Anterior Cingulate Cortex Dorsal Premotor Cortex Supplemental Motor Area Sham Primary Motor Cortex | 1 |
| Subject 7 Received rTMS intervention in the following order, each at 0.2Hz for 15 minutes:
Sham Primary Motor Cortex Dorsal Premotor Cortex Anterior Cingulate Cortex Supplemental Motor Area | 1 |
| Subject 8 Received rTMS intervention in the following order, each at 0.2Hz for 15 minutes:
Anterior Cingulate Cortex Supplemental Motor Area Primary Motor Cortex Sham Dorsal Premotor Cortex | 1 |
| Total | 8 |
Baseline characteristics
| Characteristic | Subject 1 | Subject 2 | Subject 3 | Subject 4 | Subject 5 | Subject 6 | Subject 7 | Subject 8 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 33 years | 60 years | 67 years | 31 years | 55 years | 41 years | 65 years | 72 years | 53 years |
| Cortical Silent Period (CSP) | 169.10 milliseconds | 153.70 milliseconds | 133.28 milliseconds | 78.10 milliseconds | 136.92 milliseconds | 76.24 milliseconds | 113.16 milliseconds | 99.76 milliseconds | 105.03 milliseconds |
| Dorsal Premotor-Motor Cortical Inhibition (DPMi) | 213 Percentage | 127.50 Percentage | 68.10 Percentage | 71.60 Percentage | NA Percentage | NA Percentage | 67.80 Percentage | 72.30 Percentage | NA Percentage |
| Region of Enrollment United States | 1 participants | 1 participants | 1 participants | 1 participants | 1 participants | 1 participants | 1 participants | 1 participants | 8 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants |
| TWSTRS Severity (Toronto Western Spasmodic Torticollis Rating Scale) | 20 units on a scale | 9 units on a scale | 8 units on a scale | 14 units on a scale | 21 units on a scale | 20 units on a scale | 12 units on a scale | 16 units on a scale | 15 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was used to assess severity of disease. The score for this section ranges from 0 (absence of severity) to 35 (maximum severity).
Time frame: Change from baseline pre-intervention TWSTRS score to post-intervention within 1 hour of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Motor Cortex rTMS | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | -3.0 units on a scale | Standard Deviation 4.8 |
| Anterior Cingulate rTMS | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | 0.25 units on a scale | Standard Deviation 1.7 |
| Dorsal Premotor rTMS | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | -2.9 units on a scale | Standard Deviation 3.4 |
| Supplemental Motor Area rTMS | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | -1.5 units on a scale | Standard Deviation 3.2 |
| Sham rTMS | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | -0.5 units on a scale | Standard Deviation 1.1 |
Secondary
Composite Measure of Patient Rating of Symptoms and Tolerability
This measure will confirm the intervention tolerability by the patient. He/she scored the tolerability from 0-10, 0 being completely tolerable and 10 completely intolerable.
Time frame: Assessment completed immediately after rTMS treatment session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Motor Cortex rTMS | Composite Measure of Patient Rating of Symptoms and Tolerability | 1.6 units on a scale | Standard Deviation 1.8 |
| Anterior Cingulate rTMS | Composite Measure of Patient Rating of Symptoms and Tolerability | 1.6 units on a scale | Standard Deviation 2.8 |
| Dorsal Premotor rTMS | Composite Measure of Patient Rating of Symptoms and Tolerability | 1.5 units on a scale | Standard Deviation 2.7 |
| Supplemental Motor Area rTMS | Composite Measure of Patient Rating of Symptoms and Tolerability | 0.9 units on a scale | Standard Deviation 1.1 |
| Sham rTMS | Composite Measure of Patient Rating of Symptoms and Tolerability | 0.8 units on a scale | Standard Deviation 1 |
Secondary
Dorsal Premotor-motor Inhibition (dPMI)
Time frame: Change from baseline dPMI to post-intervention within 1 hour of treatment
Population: two subjects did not have dPMI measured
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Primary Motor Cortex rTMS | Dorsal Premotor-motor Inhibition (dPMI) | 57.50 percentage | Standard Deviation 40.5 |
| Anterior Cingulate rTMS | Dorsal Premotor-motor Inhibition (dPMI) | 2.10 percentage | Standard Deviation 24.5 |
| Dorsal Premotor rTMS | Dorsal Premotor-motor Inhibition (dPMI) | 21.08 percentage | Standard Deviation 42.5 |
| Supplemental Motor Area rTMS | Dorsal Premotor-motor Inhibition (dPMI) | 32.21 percentage | Standard Deviation 53.5 |
| Sham rTMS | Dorsal Premotor-motor Inhibition (dPMI) | 19.71 percentage | Standard Deviation 80 |