Cervical Dystonia
Conditions
Keywords
dystonia, cervical dystonia, Botox, idiopathic primary cervical dystonia
Brief summary
The purpose of this study is to determine how to improve treatment of patients with cervical dystonia who have not been helped with standard Botox injections. This study is for patients with cervical dystonia who have not benefited from treatment with Botox using conventional single lead electromyographic (EMG) techniques for injection. The study aim is to see if these patients may have significantly more benefit if their Botox is injected into muscles that have been chosen with a multi-channel EMG mapping study of the neck prior to Botox injection.
Detailed description
The most common type of primary late-onset dystonia is cervical dystonia. Botulinum toxin A (BTX-A) injections are a safe and effective treatment for cervical dystonia in a majority of patients, however, a significant minority of patients (between 15 and 25%) have a suboptimal response to Botulinum toxin therapy. It is unclear why some patients do not respond maximally to neurotoxin therapy. Studies using needle electromyographic mapping in the evaluation of cervical dystonia have revealed that clinical examination alone is insufficient for determining which muscles contribute to the dystonic movement. When compared to needle electromyography (EMG) mapping studies, experienced movement disorders specialists correctly identify only 59% of active muscles and believe that 25% of muscles which upon EMG evaluation are found to be quiescent, are involved in the dystonia. The selection of incorrect muscles for injection of Botulinum toxin may explain why some patients have a sub-optimal response. This study seeks to measure outcomes when the muscles involved in dystonia are identified using mapping via an 8-12 channel EMG. In the proposed study, the most involved/active dystonic muscles will be correctly identified through simultaneous 8-12 channel mapping resulting in a more informed injection strategy, which may improve response to Botulinum toxin A treatment as compared to single lead EMG based injections. This study changes routine clinical care only by adding the step of studying the muscles of the neck with simultaneous EMG mapping to allow a more objective injection strategy.
Interventions
DRUGBotulinum toxin A
All patients will be treated with Botox using both single-channel and multi-channel EMG mapping.
Sponsors
Allergan
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects, 18 to 75 years of age. * Ability to follow study instructions and complete all required visits. * Subject meets diagnostic criteria for idiopathic primary cervical dystonia. * Subject has at least moderate severity Cervical Dystonia, with a baseline rating of at least 30 on the total TWSTRS and at least 15 on the TWSTRS motor severity subsection. * Patients have had a suboptimal response to 2 previous Botulinum toxin injections at an outside facility. * Patients will not have received Botulinum toxin within 16 weeks of the start of the study. * In order to not confound the clinical response to BTX-A injections, all patients enrolled must have been on a stable medication regimen for 30 days. If they are not on medication at the initiation of the study, they will not be started on medication. Patients must be on the same medication regimen through the entire study including assessment of both single lead EMG based injections and mapping based injections. Medications cannot be stopped during the study to avoid confounding the clinical response to BTX-A.
Exclusion criteria
* Known allergy or sensitivity to any of the components in BTX-A. * Uncontrolled clinically significant medical condition other than the condition under evaluation * Females with a positive pregnancy test, or who are breast-feeding, planning a pregnancy during the study, who think that they may be pregnant at the start of the study or females of childbearing potential who are unable or unwilling to use a reliable form of contraception during the study. * Participation in another medication or device study or within 3 months of enrollment in this study. * Patients know to have a positive frontalis test or have previously tested positive for the presence of BTX-A antibodies will be excluded. * Any known evidence of cervical contractures or significant spinal deformity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pre- and Post-injection Toronto Western Spasmodic Torticollis Rating Scale(TWSTRS): Global Clinical Impression Scale (GCI); Visual Analog Scale(VAS) | pre-injection, week 16, 20, 36, and 40 | — |
| Mean Percentage Change in Total Toronto Western Spasmodic Torticollis Rating Scale | baseline and 48 weeks | Mean Percentage change in Toronto Western Spasmodic Torticollis Rating Scale. This scale ranges from 0 (normal) to 85 (very severe). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard EMG Guided Injections Then Multi-channel All patients will undergo injection using conventional single channel EMG-guided technique. This will be used as a baseline for multi-channel mapping-based injections. Patients will be randomized to undergo single-channel vs. multi-channel assessment upon study entry and will then cross over to the alternate arm. | 5 |
| Multi-channel EMG-guided Botox Injection Then Single Channel Patients will receive multi-channel EMG-guided Botox injection before or after they have been treated with single-channel EMG-guided Botox, depending on which group they are assigned in the cross-over design. | 5 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (Week 0-24) | Frontalis Test Negative | 0 | 1 |
Baseline characteristics
| Characteristic | Multi-channel EMG-guided Botox Injection Then Single Channel | Standard EMG Guided Injections Then Multi-channel | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| Age, Continuous | 54.7 years STANDARD_DEVIATION 5.1 | 55.4 years STANDARD_DEVIATION 5.2 | 55.4 years STANDARD_DEVIATION 5.2 |
| Region of Enrollment United States | 5 participants | 5 participants | 10 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 0 / 10 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 |
Outcome results
Primary
Mean Percentage Change in Total Toronto Western Spasmodic Torticollis Rating Scale
Mean Percentage change in Toronto Western Spasmodic Torticollis Rating Scale. This scale ranges from 0 (normal) to 85 (very severe).
Time frame: baseline and 48 weeks
Population: All participants that completed all phases of the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard EMG-guided Botox Injection | Mean Percentage Change in Total Toronto Western Spasmodic Torticollis Rating Scale | 9 percent change | Standard Deviation 20.8 |
| Multi-channel EMG-guided Botox Injection | Mean Percentage Change in Total Toronto Western Spasmodic Torticollis Rating Scale | 23.5 percent change | Standard Deviation 15.7 |
Primary
Pre- and Post-injection Toronto Western Spasmodic Torticollis Rating Scale(TWSTRS): Global Clinical Impression Scale (GCI); Visual Analog Scale(VAS)
Time frame: pre-injection, week 16, 20, 36, and 40
Population: PI left institution. Efforts to contact PI to obtain data have been unsuccessful.