Cervical Dystonia
Conditions
Keywords
Cervical Dystonia, Botox
Brief summary
This study aims to compare Botox injections without Physical Therapy sessions to Botox injections combined with Physical Therapy sessions for treatment of Cervical Dystonia. It is expected that Botox combined with Physical Therapy will improve Cervical Dystonia symptoms and quality of life more than Botox alone. It is also expected that Botox combined with Physical Therapy will enhance neuroplasticity, or the ability of the brain to make new connections, more than Botox alone at 4-5 weeks, and remain improved at 12 weeks, after Botox injection.
Detailed description
The study will recruit primary cervical dystonia patients (age 18-80) who are stable on Allergan botulinum toxin type A (Botox). Patients will be randomized to receive their typical Botox injection alone, or with physical therapy. At Baseline, disease characteristics (as measured by the Toronto Western Spasmodic Torticollis Rating Scale, or TWSTRS, and the Clinical Global Impression of Severity, or CGIS) will be measured, along with quality of life (from the Short Health 36 Survey Form 36, or SF-36). One subscale of the TWSTRS will be videotaped to be later evaluated by blinded movement disorder specialists. A pain scale will also be completed and range of head motion will be measured using a device similar to a protractor (called a goniometer). An individualized Botox injection will be administered, as well as transcranial magnetic stimulation (TMS) to measure neuroplasticity, or the ability of the brain to make new connections. If randomized to receive physical therapy, participants will also receive instructions to perform physical therapy exercises five times per week by a physical therapist who specializes in movement disorders. The investigator will call weekly to check how the participant is doing with the exercise program. The same procedures outlined above will also be performed at 5 weeks past baseline, and at 12 weeks (except for the Botox injection, which will only be given at baseline and 12 weeks).
Interventions
DRUGBotox injection
Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms
BEHAVIORALPhysical Therapy
Participants will undergo physical therapy sessions with a physical therapist trained in movement disorders. Participants will be instructed to continue these exercises five times per week, and will be called weekly by the investigator to check progress.
PROCEDURETranscranial magnetic stimulation (TMS)
For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.
Sponsors
American Academy of Neurology
National Ataxia Foundation
American Brain Foundation
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18-80 with a diagnosis of Cervical Dystonia, which will be confirmed by a movement disorders specialist * Positive response to at least two prior treatments with Botox as indicated by an improvement in Clinical Global Improvement Scale. * Received last dose of Botox a minimum of 12 weeks prior to baseline visit.
Exclusion criteria
* Any conditions that would contraindicate transcranial magnetic stimulation (for example, pregnancy or epilepsy) * Any secondary, fixed, post-traumatic, or psychogenic dystonia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | absolute value at Week 12 | The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is a measure of symptoms, pain, and disability related to Cervical Dystonia. The total TWSTRS scale includes a global outcome score (total score) and scores on each of 3 subscales for severity (0-35), disability (0-30), and pain (0-20), which are summed together for a total score (0-85), with higher scores indicating greater impairment. The TWSTRS is completed by a neurologist who visually assesses the patient's symptoms, and asks the patient to self-report on pain and disability. |
| SF-36 Physical Functioning Subscore | absolute value at Week 12 | The Short Form 36-Item Health Scale (SF-36) is a health survey with 36 questions that is self-reported by the study participant. It contains 8 subscales, one of which is Physical Functioning, calculated from 10 of the 36 questions. Different questions have different score ranges and valences. Therefore, their response for each question is linearly transformed to a value of 0-100 (for example, choosing response 3 on a scale of 1-5 is transformed to 60). These ten values are then averaged to generate the Physical Functioning subscore, ranging from 0-100. The higher the response value and the subscore, the higher degree of physical functioning. More details on RAND SF-36 scoring here: https://www.rand.org/health-care/surveys\_tools/mos/36-item-short-form/scoring.html |
| Clinical Global Impression Scale (CGIS) | absolute value at Week 12 | This scale is an investigator-rated scale that measures illness severity on a single 7-point scale (1-7). Higher scores represent greater severity of illness. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean MEP After Paired Associative Stimulation (PASmean) | absolute value at week 12 | A standard transcranial magnetic stimulation (TMS) paired associative stimulation (PAS) protocol was used to measure of neuroplasticity (the ability of the brain to form new connections). A nerve stimulator was placed on the wrist of the right hand to stimulate the median and ulnar nerves, set at the lowest intensity where the right thumb begins to twitch. An EMG sensor was placed over the abductor pollicis brevis muscle to measure muscle contractions. A magnetic coil was placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. 90 pairs of TMS and nerve stimulator pulses were applied. Then the motor evoked potential (MEP) from a single TMS pulse recorded from the surface EMG of the abductor pollicis brevis muscle was determined immediately, at 15 min and at 30 min after completion of the PAS protocol. The mean of these MEPs (PASmean) was compared between baseline and followup. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale | absolute value at 12 weeks | This is a single item scale, on which participants will mark the level of pain from 0-10. Higher score represents more severe pain. |
| Cervical Range of Motion Measurement | absolute value at 12 weeks was calculated | Participants will be asked to sit in a chair and move the head to the left, to the right, to the front, and to the back. Then, participants be asked to tilt the head from side to side. A goniometer will be used to measure how far the head is able to move. The goniometer is similar to a protractor that measures magnitude of angle. A greater number indicates a greater range of motion. The minimum score would be 0, with no definite maximum (would not clinically be expected to exceed 70 degrees). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Botox Only Participants randomized to receive Botox injections alone.
Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms
Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head. | 8 |
| Botox Plus Physical Therapy Participants randomized to receive Botox injection combined with Physical Therapy
Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms
Physical Therapy: Participants will undergo physical therapy sessions with a physical therapist trained in movement disorders. Participants will be instructed to continue these exercises five times per week, and will be called weekly by the investigator to check progress.
Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Total | Botox Plus Physical Therapy | Botox Only |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 5 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 3 Participants | 3 Participants |
| Age, Continuous | 64.5 years STANDARD_DEVIATION 5.5 | 64.7 years STANDARD_DEVIATION 5.4 | 64.3 years STANDARD_DEVIATION 5.2 |
| Region of Enrollment United States | 16 participants | 8 participants | 8 participants |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 4 Participants |
| TWSTRS pain | 3.8 units on a scale STANDARD_DEVIATION 1.2 | 3.8 units on a scale STANDARD_DEVIATION 1.5 | 4 units on a scale STANDARD_DEVIATION 1.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Clinical Global Impression Scale (CGIS)
This scale is an investigator-rated scale that measures illness severity on a single 7-point scale (1-7). Higher scores represent greater severity of illness.
Time frame: absolute value at Week 12
Population: mean difference was calculated
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botox Only | Clinical Global Impression Scale (CGIS) | 3 units on a scale | Standard Deviation 1 |
| Botox Plus Physical Therapy | Clinical Global Impression Scale (CGIS) | 2 units on a scale | Standard Deviation 1 |
Primary
SF-36 Physical Functioning Subscore
The Short Form 36-Item Health Scale (SF-36) is a health survey with 36 questions that is self-reported by the study participant. It contains 8 subscales, one of which is Physical Functioning, calculated from 10 of the 36 questions. Different questions have different score ranges and valences. Therefore, their response for each question is linearly transformed to a value of 0-100 (for example, choosing response 3 on a scale of 1-5 is transformed to 60). These ten values are then averaged to generate the Physical Functioning subscore, ranging from 0-100. The higher the response value and the subscore, the higher degree of physical functioning. More details on RAND SF-36 scoring here: https://www.rand.org/health-care/surveys\_tools/mos/36-item-short-form/scoring.html
Time frame: absolute value at Week 12
Population: mean difference between two groups calculated
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botox Only | SF-36 Physical Functioning Subscore | 68 units on a scale | Standard Deviation 16 |
| Botox Plus Physical Therapy | SF-36 Physical Functioning Subscore | 88 units on a scale | Standard Deviation 18 |
Primary
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is a measure of symptoms, pain, and disability related to Cervical Dystonia. The total TWSTRS scale includes a global outcome score (total score) and scores on each of 3 subscales for severity (0-35), disability (0-30), and pain (0-20), which are summed together for a total score (0-85), with higher scores indicating greater impairment. The TWSTRS is completed by a neurologist who visually assesses the patient's symptoms, and asks the patient to self-report on pain and disability.
Time frame: absolute value at Week 12
Population: mean difference between two groups was calculated
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botox Only | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | 28 total score on a scale | Standard Deviation 10.2 |
| Botox Plus Physical Therapy | Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) | 20.1 total score on a scale | Standard Deviation 9.8 |
Secondary
Mean MEP After Paired Associative Stimulation (PASmean)
A standard transcranial magnetic stimulation (TMS) paired associative stimulation (PAS) protocol was used to measure of neuroplasticity (the ability of the brain to form new connections). A nerve stimulator was placed on the wrist of the right hand to stimulate the median and ulnar nerves, set at the lowest intensity where the right thumb begins to twitch. An EMG sensor was placed over the abductor pollicis brevis muscle to measure muscle contractions. A magnetic coil was placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. 90 pairs of TMS and nerve stimulator pulses were applied. Then the motor evoked potential (MEP) from a single TMS pulse recorded from the surface EMG of the abductor pollicis brevis muscle was determined immediately, at 15 min and at 30 min after completion of the PAS protocol. The mean of these MEPs (PASmean) was compared between baseline and followup.
Time frame: absolute value at week 12
Population: mean difference was calculated
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botox Only | Mean MEP After Paired Associative Stimulation (PASmean) | 1.7 millivolts | Standard Deviation 0.5 |
| Botox Plus Physical Therapy | Mean MEP After Paired Associative Stimulation (PASmean) | 1.3 millivolts | Standard Deviation 0.6 |
Other Pre-specified
Cervical Range of Motion Measurement
Participants will be asked to sit in a chair and move the head to the left, to the right, to the front, and to the back. Then, participants be asked to tilt the head from side to side. A goniometer will be used to measure how far the head is able to move. The goniometer is similar to a protractor that measures magnitude of angle. A greater number indicates a greater range of motion. The minimum score would be 0, with no definite maximum (would not clinically be expected to exceed 70 degrees).
Time frame: absolute value at 12 weeks was calculated
Population: mean difference was calculated
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botox Only | Cervical Range of Motion Measurement | 25 Angle in degrees | Standard Deviation 14 |
| Botox Plus Physical Therapy | Cervical Range of Motion Measurement | 26 Angle in degrees | Standard Deviation 14 |
Other Pre-specified
Visual Analog Scale
This is a single item scale, on which participants will mark the level of pain from 0-10. Higher score represents more severe pain.
Time frame: absolute value at 12 weeks
Population: mean difference was calculated
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botox Only | Visual Analog Scale | 6 units on a scale | Standard Deviation 3 |
| Botox Plus Physical Therapy | Visual Analog Scale | 4 units on a scale | Standard Deviation 2 |