Noninvasive Brain Stimulation for Cervical Dystonia (NetworkStim)

The Effect of Noninvasive Brain Stimulation on Symptoms of Cervical Dystonia

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Cervical Dystonia
• Intervention / Treatment: Device: Active continuous theta-burst stimulation; Device: Sham continuous theta-burst stimulation

Detailed Description

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. 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.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daniel T Corp, PhD; Phone Number: +393445660971; Email: danieltcorp@gmail.com
• Study Contact Backup: Name: Ambra Salvati; Phone Number: +393491028595; Email: ambra.salvati@unicampus.it

Study Locations

• Italy
  • Roma
    • Roma, Roma, Italy, 00128
      • Università Campus Bio-Medico
      • Contact: Vincenzo Di Lazzaro, MD; Phone Number: +39 06225411220; Email: v.dilazzaro@policlinicocampus.it
      • Contact: Ambra Salvati, Psy.D.; Phone Number: +39 3491028595; Email: ambra.salvati@unicampus.it
      • Sub-Investigator: Daniel T Corp, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Aged between 18 and 85 years
• Diagnosis of idiopathic cervical dystonia made by an expert physician
• Last botulinum toxin injection administered at least two months before the start of participation in the study (Albanese, Abbruzzese et al. 2015)

Exclusion Criteria

• Head or neck trauma occurring less than 12 months before the onset of dystonia
• Acquired dystonia (e.g., drug-induced, brain lesions or trauma)
• History of major psychiatric disorders (e.g., bipolar disorder, schizophrenia, obsessive-compulsive disorder)
• History of neurological diseases other than CD (e.g., epilepsy, Parkinson's disease)
• Other contraindications for TMS or brain MRI (e.g., metal in the head)
• Pregnant or breastfeeding women
• History of substance abuse or dependence

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active cTBS; 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; 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 Comparator: Sham cTBS; 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; Sham cTBS procedures will be identical to those in the active cTBS arm but applied using a 70mm sham TMS coil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms of cervical dystonia - TWSTRS total score	The total score on the Toronto Western Spasmodic Torticollis Rating Scale	For a single patient, a minimum of 6 weeks and a maximum of 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms of cervical dystonia - TWSTRS subscales	The scores on each of the subscales of the Toronto Western Spasmodic Torticollis Rating Scale (severity, disability, pain)	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	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	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	For a single patient, 10 days. Pre and post cTBS
Fahn Tolosa Marin tremor scale	Measurement of head and neck tremor	For a single patient, a minimum of 6 weeks and a maximum of 16 weeks
Global dystonia severity rating scale	Measurement of dystonia in other body parts	For a single patient, a minimum of 6 weeks and a maximum of 16 weeks

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Campus Bio-Medico
• Collaborators: European Commission
• Investigators: Principal Investigator: Vincenzo Di Lazzaro, MD, Campus Bio-Medico Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 6, 2026
• Primary Completion (Estimated): May 6, 2028
• Study Completion (Estimated): May 6, 2028

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Transcranial magnetic stimulation; Cervical dystonia; Somatosensory cortex; Continuous theta-burst stimulation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Dyskinesias; Dystonia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Torticollis
• Other Study ID Numbers: NetworkStim 270.25 CET2 cbm

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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
• IPD Sharing Time Frame: The Study Protocol, SAP, and ICF will be made available with this pre-registration prior to study commencement. Generated participant data and code will be available after the pre-print of the publication describing it are released. There is no time limit for how long the data will be made available.
• IPD Sharing Access Criteria: Public access as per the terms of clinicaltrials.gov and the OpenNeuro and Big NIBS data repositories.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No