Accelerated TMS for Hand Dystonia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Duke University
Must not be taking: Anticholinergics, Benzodiazepines, Muscle relaxants
Disqualifiers: Other dystonia, Parkinsonism, Seizure, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?
This study aims to investigate the impact of accelerated transcranial magnetic stimulation (TMS) on brain function and behavior in patients with focal hand dystonia. Previous research demonstrated that individualized TMS improved dystonic behavior after one session. Building on this, the current study administers four TMS sessions in a day, with assessments conducted in four weeks, twelve weeks, and 20 weeks after each session. The research involves 8 in-person and 6 virtual visits focused on functional MRI brain scans and writing behavior analysis. The potential risk of seizures from TMS is mitigated through careful screening, adhering to safety guidelines. The study's main benefit is enhancing dystonic behavior and deepening the understanding of brain changes caused by TMS in focal hand dystonia, paving the way for further advancements in clinical therapy for this condition.
Will I have to stop taking my current medications?
Yes, you will need to stop taking medications used for treating dystonia symptoms, such as anticholinergics, benzodiazepines, and muscle relaxants, at least one month before the study.
What data supports the effectiveness of the treatment Accelerated TMS for Hand Dystonia?
Research shows that theta burst stimulation, a component of Accelerated TMS, can lead to improvements in dystonia symptoms by modifying brain circuits involved in movement control. In cervical dystonia, a similar condition, cerebellar theta burst stimulation resulted in a small but significant clinical improvement, suggesting potential benefits for hand dystonia as well.12345
Is Accelerated TMS generally safe for humans?
Research on repetitive transcranial magnetic stimulation (rTMS) and related techniques like Theta-Burst Stimulation shows they are generally safe for humans, with studies often focusing on conditions like dystonia. While these studies primarily assess effectiveness, they also monitor safety, and no major safety concerns have been reported in the context of these treatments.35678
How does the treatment Accelerated TMS differ from other treatments for hand dystonia?
Accelerated TMS (repetitive transcranial magnetic stimulation) is unique because it uses magnetic fields to stimulate specific brain areas, potentially improving brain plasticity and connectivity, which are often altered in dystonia. Unlike traditional treatments, it targets the brain's motor and sensory pathways non-invasively, offering a novel approach to managing symptoms.12359
Eligibility Criteria
This trial is for adults over 18 with isolated focal hand dystonia, confirmed by a neurologist. Participants must be right-handed, able to give informed consent and literate. Excluded are those with other movement disorders or seizure history, recent drug use or certain treatments like TMS therapy, botulinum toxin injections, specific medications for dystonia symptoms, and recent hand therapy.Inclusion Criteria
You primarily use your right hand for tasks.
I am 18 years old or older.
Diagnosed with isolated focal hand by a neurologist.
See 2 more
Exclusion Criteria
I have a history of seizures.
I have been diagnosed with a movement disorder other than dystonia.
You have any reasons that make it unsafe for you to have a MRI or TMS.
See 6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive accelerated TMS sessions, with four sessions administered in a single day
1 day
2 visits (in-person)
Assessment
Participants undergo functional MRI brain scans and engage in writing tasks to evaluate changes in brain function and behavior
4 weeks
6 visits (virtual), 6 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, with assessments at 12, 20, 24, 32, and 40 weeks
40 weeks
Treatment Details
Interventions
- Accelerated TMS (Procedure)
Trial OverviewThe study tests accelerated transcranial magnetic stimulation (TMS) on patients with focal hand dystonia. It involves four TMS sessions in one day and assesses the impact on brain function and writing behavior immediately after, at two weeks and twelve weeks post-treatment using functional MRI scans.
Participant Groups
2Treatment groups
Active Control
Placebo Group
Group I: TMS to primary somatosensory cortexActive Control1 Intervention
Participants received TMS sessions at primary somatosensory cortex
Group II: TMS at low amplitude to primary somatosensory cortexPlacebo Group1 Intervention
Participants receive TMS at a cortical target at smaller amplitude
Accelerated TMS is already approved in United States, European Union, United Kingdom for the following indications:
🇺🇸 Approved in United States as rTMS for:
- Major Depressive Disorder
- Obsessive Compulsive Disorder
🇪🇺 Approved in European Union as rTMS for:
- Major Depressive Disorder
- Obsessive Compulsive Disorder
🇬🇧 Approved in United Kingdom as rTMS for:
- Major Depressive Disorder
- Obsessive Compulsive Disorder
- Post-Traumatic Stress Disorder
- Depersonalization Disorder
- Borderline Personality Disorder
- Addiction
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Duke University Health SystemDurham, NC
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Who Is Running the Clinical Trial?
Duke UniversityLead Sponsor
American Academy of NeurologyCollaborator
References
Primary somatosensory cortical plasticity and tactile temporal discrimination in focal hand dystonia. [2022]To investigate whether theta burst stimulation (TBS) applied over primary somatosensory cortex (S1) modulates somatosensory temporal discrimination threshold (STDT) and writing performances in patients with focal hand dystonia (FHD).
Effects of two weeks of cerebellar theta burst stimulation in cervical dystonia patients. [2018]Dystonia is generally regarded as a disorder of the basal ganglia and their efferent connections to the thalamus and brainstem, but an important role of cerebellar-thalamo-cortical (CTC) circuits in the pathophysiology of dystonia has been invoked. Here in a sham controlled trial, we tested the effects of two-weeks of cerebellar continuous theta burst stimulation (cTBS) in a sample of cervical dystonia (CD) patients. Clinical evaluations were performed by administering the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). We used TMS to measure the inhibitory connectivity between the cerebellum and the contralateral motor cortex (cerebellar brain inhibition [CBI]), and the excitability of the contralateral primary motor cortex assessing intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Paired associative stimulation (PAS) was tested to evaluate the level and the topographical specificity of cortical plasticity, which is abnormally enhanced and non-focal in CD patients. Two weeks of cerebellar stimulation resulted in a small but significant clinical improvement as measured by the TWSTRS of approximately 15%. Cerebellar stimulation modified the CBI circuits and reduced the heterotopic PAS potentiation, leading to a normal pattern of topographic specific induced plasticity. These data provide novel evidence CTC circuits could be a potential target to partially control some dystonic symptoms in patients with cervical dystonia.
Abnormal cerebellar connectivity and plasticity in isolated cervical dystonia. [2020]There is increasing evidence that supports the role of the cerebellum in the pathophysiology of dystonia. We used transcranial magnetic stimulation to test the hypothesis that patients with cervical dystonia may have a disrupted cerebellar cortical connectivity at rest, and that cerebellar plasticity is altered too. We enrolled 12 patients with isolated cervical dystonia and 13 controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right cerebellum and the left primary motor area. Changes in the amplitude of motor evoked potentials were analysed. Continuous and intermittent Theta Burst Stimulation over the cerebellum was also applied. The effects of these repetitive protocols on cortical excitability, on intra-cortical circuits and on cerebellar cortical inhibition were analysed. In healthy subjects, but not in dystonic patients, a conditioning stimulus over the cerebellum was able to inhibit the amplitude of the motor evoked potentials from primary motor cortex. In healthy subjects continuous and intermittent cerebellar Theta Burst Stimulation were able to decrease and increase respectively motor cortex excitability. Continuous Theta Burst Stimulation was able to abolish the cerebellar cortical inhibition observed in basal condition. These effects were not observed in patients with cervical dystonia. Cerebellar cortical connectivity and cerebellar plasticity is altered at rest in patients with cervical dystonia.
Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia. [2018]To investigate the cerebellar inhibitory influence on the primary motor cortex in patients with focal dystonia using a cerebellar continuous theta-burst stimulation protocol (cTBS) and to evaluate any relationship with movement abnormalities.
Abnormal experimentally- and behaviorally-induced LTP-like plasticity in focal hand dystonia. [2013]Idiopathic focal hand dystonia (FHD) arises from abnormal plasticity in the primary motor cortex (M1) possibly reflecting abnormal sensori-motor integration processes. In this transcranial magnetic stimulation (TMS) study in FHD, we evaluated changes in motor evoked potentials (MEPs) after intermittent theta burst stimulation (iTBS) and paired associative stimulation (PAS), techniques that elicit different forms of experimentally-induced long-term potentiation (LTP)-like plasticity in M1. We also examined behaviorally-induced LTP-like plasticity as reflected by early motor learning of a simple motor task. We studied 14 patients with FHD and 14 healthy subjects. MEPs were recorded before and after iTBS and PAS at the 25 ms interstimulus interval (PAS(25)) in separate sessions. Subjects did a simple motor task entailing repetitive index finger abductions. To measure early motor learning we tested practice-related improvement in peak velocity and peak acceleration. In FHD patients iTBS failed to elicit the expected MEP changes and PAS(25) induced abnormally increased MEPs in target and non-target muscles. In the experiment testing early motor learning, patients lacked the expected practice-related changes in kinematic variables. In FHD, the degree of early motor learning correlated with patients' clinical features. We conclude that experimentally-induced (iTBS and PAS) and behaviorally-induced LTP-like plasticity are both altered in FHD.
[Efficacy and safety of transcranial magnetic stimulation in the treatment of rare forms of muscular dystonia]. [2018]To evaluate the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) for the treatment of patients with dystonia.
Pseudo-bilateral hand motor responses evoked by transcranial magnetic stimulation in patients with deep brain stimulators. [2019]In 3 of 5 patients with dystonia and bilaterally implanted deep brain stimulating electrodes, focal transcranial magnetic stimulation (TMS) of one motor cortex elicited bilateral hand motor responses. The aim of this study was to clarify the origin of these ipsilateral responses.
Abnormalities in motor cortical plasticity differentiate manifesting and nonmanifesting DYT1 carriers. [2007]A mutation in the DYT1 gene causes dominantly inherited childhood-onset primary dystonia, but intriguingly, only 30 to 40% of those who carry the mutation ever develop symptoms. We have used the unique model provided by this group of patients to investigate the hypothesis that abnormalities in brain plasticity underlie the pathophysiology of primary dystonia. We recruited 8 DYT1 gene carriers with dystonia, 6 DYT1 gene carriers without dystonia, 6 patients with sporadic primary dystonia (torticollis), and 10 healthy control subjects. Groups were age-matched. We compared the effect in these groups of subjects of repetitive transcranial magnetic stimulation (rTMS) delivered to the motor cortex, by assessing changes in corticospinal excitability following rTMS. rTMS was given in the form of theta burst stimulation (TBS) using the inhibitory protocol "cTBS" (total of 300 pulses in 50-Hz bursts given every 5Hz). DYT1 gene carriers with dystonia and subjects with torticollis had a significantly prolonged response to rTMS in comparison with healthy subjects. In contrast, DYT1 gene carriers without dystonia had no significant response to rTMS. These data demonstrate an excessive response to an experimental "plasticity probing protocol" in subjects with dystonia, but a lack of response in genetically susceptible individuals who have not developed dystonia. These preliminary data suggest that the propensity to undergo plastic change may affect the development of symptoms in genetically susceptible individuals and that this may be an important mechanism in the pathogenesis of primary dystonia in general.
Exploring the connections between basal ganglia and cortex revealed by transcranial magnetic stimulation, evoked potential and deep brain stimulation in dystonia. [2022]We review the findings for motor cortical excitability, plasticity and evoked potentials in dystonia. Plasticity can be induced and assessed in cortical areas by non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and the invasive technique of deep brain stimulation (DBS), which allows access to deep brain structures. Single-pulse TMS measures have been widely studied in dystonia and consistently showed reduced silent period duration. Paired pulse TMS measures showed reduced short and long interval intracortical inhibition, interhemispheric inhibition, long-latency afferent inhibition and increased intracortical facilitation in dystonia. Repetitive transcranial magnetic stimulation (rTMS) of the premotor cortex improved handwriting with prolongation of the silent period in focal hand dystonia patients. Continuous theta-burst stimulation (cTBS) of the cerebellum or cTBS of the dorsal premotor cortex improved dystonia in some studies. Plasticity induction protocols in dystonia demonstrated excessive motor cortical plasticity with the reduction in cortico-motor topographic specificity. Bilateral DBS of the globus pallidus internus (GPi) improves dystonia, associated pain and functional disability. Local field potentials recordings in dystonia patients suggested that there is increased power in the low-frequency band (4-12 Hz) in the GPi. Cortical evoked potentials at peak latencies of 10 and 25 ms can be recorded with GPi stimulation in dystonia. Plasticity induction protocols based on the principles of spike timing dependent plasticity that involved repeated pairing of GPi-DBS and motor cortical TMS at latencies of cortical evoked potentials induced motor cortical plasticity. These studies expanded our knowledge of the pathophysiology of dystonia and how cortical excitability and plasticity are altered with different treatments such as DBS.