An interventional study of Active continuous theta-burst stimulation and Sham continuous theta-burst stimulation in Cervical Dystonia, sponsored by Fondazione Policlinico Universitario Campus Bio-Medico. Recruiting at 1 site in Italy. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2026-09-17.
Sponsored by Fondazione Policlinico Universitario Campus Bio-Medico · Not applicable, Interventional, and Treatment
The primary aim of this study is to assess whether continuous theta-burst stimulation (cTBS) can be helpful in reducing symptoms of idiopathic cervical dystonia. This will be a parallel-group, randomised, sham-controlled, double blind clinical trial. Patients and investigators measuring patient symptoms clinical scales will be blinded from allocation group, investigators delivering the intervention will not be blinded, as this is not feasible. Real cTBS will be compared to sham cTBS, with patients allocated to these two groups with a 1:1 recruitment ratio.
Bilateral cTBS will be delivered four times daily, over eight days, for a total of 32 bilateral cTBS sessions. The primary outcome is the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). This will be administered at T1 (pre-cTBS), T2 (day 10, following days 2-9 where patients received the intervention), T3 (2 weeks post the final session of cTBS), and T4 (4-5 weeks post the final session of cTBS).
Secondary outcomes will be the TWSTRS subscales (severity, disability, pain), Quality of Life scale, Global dystonia severity rating scale (GDS), Fahn Tolosa Marin (FTM) modified (to include only questions relevant to head/neck tremor) tremor scale, kinematic data of patient's movement patterns, motor evoked potentials (MEPs), and resting-state fMRI data (fMRI).
Cervical dystonia (CD) is the most common form of dystonia and is characterised by excessive and involuntary muscle contractions of the muscles in the neck. Whilst botulinum neurotoxin (BoNT) injections to the affected muscles can provide therapeutic relief to CD patients, up to one-third of patients report an inadequate response to treatment. In more severe cases, deep brain stimulation (DBS) of the globus pallidus interna (GPi) or subthalamic nucleus is an effective treatment for CD symptoms, directly and indirectly modulating networks thought to be abnormal in CD. Transcranial magnetic stimulation (TMS) trials have previously been conducted to investigate its potential to ameliorate CD symptoms. These studies have shown limited success, with small sample sizes, and variable results. A major factor limiting the more effective use of TMS in CD is that it is not yet known where to target with TMS, given the many structures implicated in the neurobiology of the disorder. A prior study using lesion network mapping in CD attempted to address this issue by localising a brain network connected to lesions causing CD. Corp, et al. demonstrated that although causal lesions were located throughout the brain, all lesions were functionally connected to a brain network involving positive connectivity to the cerebellum and negative connectivity to the somatosensory cortex (S1). Preliminary work from our group examined the effect of targeting this lesion network mapping-derived S1 cluster using TMS. First, a single session of continuous theta-burst stimulation (cTBS) to the S1 indicated target engagement, as demonstrated by abnormal metabolic response in CD patients, and next, a pilot trial of 10 days of daily cTBS demonstrated a 12% reduction in CD symptoms. The primary aim of this study is to assess whether a higher-dose of (4x daily) cTBS can increase therapeutic effect.
Exclusion Criteria
The patients of this group will receive 4 sessions of bilateral somatosensory cortex cTBS per day for 8 days
Device: Active continuous theta-burst stimulation
The patients of this group will receive 4 sessions of bilateral somatosensory cortex cTBS per day for 8 days, delivered using a sham TMS coil.
Device: Sham continuous theta-burst stimulation
Continuous theta-burst stimulation (cTBS) will be delivered using a Magstim Rapid machine connected to a 70mm cooled coil at 80% of a participants resting motor threshold (RMT). cTBS will consist of three-pulse bursts at 50Hz repeated every 200ms (5Hz) for 40 seconds (600 pulses total) (Huang, Edwards et al. 2005). All cTBS procedures will be conducted bilaterally, with application first over the left hemisphere, before moving to the right (approximately one minute will separate each hemisphere). Bilateral cTBS will be delivered four times daily, over eight days, for a total of 32 bilateral cTBS sessions. This 4x day protocol will follow prior studies in neglect patients, delivered at time intervals of 0, 15, 60, and 75 minutes (Nyffeler, Cazzoli et al. 2008, Cazzoli, Müri et al. 2012, Nyffeler, Vanbellingen et al. 2019).
Sham cTBS procedures will be identical to those in the active cTBS arm but applied using a 70mm sham TMS coil.
Symptoms of cervical dystonia - Toronto Western Spasmodic Torticollis Rating Scale total score
The total score on the Toronto Western Spasmodic Torticollis Rating Scale. Range: 0-85. Higher scores mean worse symptoms.
Time frame: For a single patient, a minimum of 6 weeks and a maximum of 16 weeks
Symptoms of cervical dystonia - Toronto Western Spasmodic Torticollis Rating Scale subscales
The scores on each of the subscales of the Toronto Western Spasmodic Torticollis Rating Scale (severity, disability, pain). Higher scores mean worse symptoms.
Time frame: For a single patient, a minimum of 6 weeks and a maximum of 16 weeks
Symptoms of cervical dystonia - kinematic recordings
Metrics of patients' head and neck movements from a wearable motion sensor. Higher scores will mean greater movement error.
Time frame: For a single patient, 10 days. Pre and post cTBS
Motor evoked potentials
Motor evoked potential amplitudes from input-output curves, measured using surface electromyography
Time frame: For a single patient, 10 days. Pre and post cTBS
Magnetic resonance imaging
Functional connectivity changes from pre-defined regions of interest in the brain
Time frame: For a single patient, 10 days. Pre and post cTBS
Fahn Tolosa Marin tremor scale
Measurement of head and neck tremor. Higher scores mean worse symptoms.
Time frame: For a single patient, a minimum of 6 weeks and a maximum of 16 weeks
Global dystonia severity rating scale
Measurement of dystonia in all body parts. Range: 0-100. Higher scores mean worse symptoms.
Time frame: For a single patient, a minimum of 6 weeks and a maximum of 16 weeks
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — For patients who provide informed consent: pseudonymised MRI data will be uploaded to the 'OpenNeuro' repository, and pseudonymised brain stimulation data and code will be uploaded to the 'Big NIBS data' repository, with the associated clinical scores
Supporting information: Study protocol, Sap, Icf, Analytic code
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Fondazione Policlinico Universitario Campus Bio-Medico