Theta Burst Transcranial Focused Ultrasound as a Novel Treatment for Cervical Dystonia

Robert Chen

Status: Enrolling

Conditions: Cervical Dystonia

Treatments: Device: LIFUS - DN Active; Device: LIFUS - GPi Active; Device: LIFUS - Sham

Study type: Interventional

Funder types: Other

Identifiers

NCT07690514

23-5741

Details and patient eligibility

About

This study is a single-blinded, randomized control study that aims to recruit 48 participants. Participants will be "randomized" into one of the study arms of the study: active stimulation to GPi, active stimulation to DN, or sham stimulation. The purpose of the study is to look into the effects of LIFUS in patients with cervical dystonia. The participation will include seven study visits, at least 24 hours apart. All study visits will take place at TWH. The first visit is a screening visit. Visits 2-6 will be on consecutive days. Visit 7 will be a week from Visit 6 or from your last day of LIFUS, whichever comes first.

Full description

Patients will be randomly assigned to one of three conditions (n =12 per condition): 1) bilateral tbLIFUS of the GPi, 2) bilateral tbLIFUS of the DN, and 3) bilateral sham tbLIFUS. Study participants will be randomized in a 1:1:1 fashion. In each group, the patients will receive tbLIFUS for five consecutive days. tbLIFUS will consist of two 120 s stimulation (one for each hemisphere, separated by 1 min). Visit 1 will consist of an anatomical MRI scan for each subject to allow accurate targeting of the GPi and DN, and for modelling the ultrasound distribution. Visit 2 will consist of baseline clinical assessments followed by pre-LIFUS rsfMRI. Immediately after, patients will receive tbLIFUS. Visits 3-5 will consist of tbLIFUS only. In Visit 6 (day 5 of stimulation), patients will receive tbLIFUS followed by rsfMRI and clinical assessments. In Visit 7, patients will undergo clinical assessments one week (+/- 3 days) after the last stimulation session in Visit 6. All patients and evaluators will be blinded to the stimulation condition. Visits 2-6 (stimulation days) will be conducted on five consecutive days. Outcome variables will be functional connectivity using rsfMRI, dystonia assessment (TWSTRS and DNMSQuest), cerebellar function assessment (Scale for the Assessment and Rating of Ataxia, SARA), head angle, tremor measurements, and phasic neck movements. SARA will be used in all conditions but will be primarily used to ensure that our protocol does not cause cerebellar dysfunction due to tbLIFUS of the DN. Tremor and phasic neck movements will be quantified with a three-axis accelerometer and neck angle will be measured using a goniometer. All clinical assessments will be video recorded and scored by two blinded movement disorders neurologists.

Enrollment: 48 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 - 90 years of age
• Confirmed diagnosis cervical dystonia
• 3 months since last botulinum toxin injection
• Stable medications in the past month

Exclusion criteria

• Has neurological disorder other than dystonia (such as compressive neuropathy, limb trauma, epilepsy)
• Cognitive deficits leading to inability to understand study purposes and risks as well as the consent information without legal trustee
• Presence of metal implanted in body that is contraindicated in MRI
• Pregnancy
• Has a previous surgical intervention to treat CD such as lesioning or a DBS system in place
• Major systemic illness or infection

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Single Blind

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48 participants in 3 patient groups

LIFUS - GPi

Experimental group

Description:

Bilateral thetaburst LIFUS stimulation to globus pallidus

Treatment:

Device: LIFUS - GPi Active

LIFUS - DN

Experimental group

Description:

Bilateral thetaburst LIFUS stimulation to dentate nucleus

Treatment:

Device: LIFUS - DN Active

LIFUS - Sham

Sham Comparator group

Description:

Bilateral Sham LIFUS stimulation

Treatment:

Device: LIFUS - Sham