rTMS and Botulinum Toxin in Primary Cervical Dystonia

University of Florida

Status: Completed

Conditions: Primary Cervical Dystonia; Dystonia

Treatments: Other: Cerebellar-brain Inhibition (CBI); Procedure: Botulinum toxin injections; Device: NeuroStar TMS therapy; Device: Sham NeuroStar TMS therapy; Other: Craniocervical Dystonia Questionnaire (CDQ-24); Other: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)

Study type: Interventional

Funder types: Other

Identifiers

NCT02542839

IRB201500341

Details and patient eligibility

About

Primary cervical dystonia (PCD) is the most common form of focal dystonia. PCD is frequently reported as a source of disability, decreased quality of life, and social stigma. Botulinum toxin (BoNT) is the gold standard treatment for PCD. The average duration of benefits from BoNT injections was about 9.5 weeks and BoNT treatment is known to provide only pure symptomatic benefits and does not seem to modify the disease pathophysiology.

The investigator plans to use repetitive transcranial magnetic stimulation (rTMS) therapy as an adjunctive therapy in combination with BoNT injections as a novel approach to treat PCD. The primary goal of this study is to compare standard treatment with BoNT versus BoNT combined with a two week course of rTMS.

Full description

rTMS refers to the application of transcranial magnetic stimulation (TMS) pulses to a specific target at predefined stimulation parameters. Repeated sessions of rTMS therapy have been demonstrated to induce cumulative persistent benefits that can last weeks after the conclusion of the rTMS sessions

The central hypothesis of this study is that rTMS therapy in PCD can potentiate the effects of BoNT injections. With the current standard treatment, the peak-dose benefits seen with BoNT are seen at about 4-6 weeks after the administration of injections. The investigator will introduce a 1 week course of rTMS around 2-8 weeks before or after BoNT or T1). The investigator will examine the effects of combined therapy at 10 weeks after BoNT and 12 weeks after BoNT injections follow-up.

Enrollment: 9 patients

Sex: All

Ages: 30 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of PCD in accordance with the Consensus Statement of the Movement Disorder Society
• Subjects who report Botulinum Toxin benefits lasting 10 weeks or less only (suboptimal benefits with standard care)

Exclusion criteria

• Pregnancy
• Active seizure disorder
• Presence of a metallic body such as pacemaker, implants, metal rods and hearing aid.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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9 participants in 2 patient groups

Real rTMS Stimulation

Experimental group

Description:

Repetitive TMS will be delivered over each cerebellar hemisphere, using a NeuroStar TMS therapy system. The coil will be positioned 3 cm lateral to the inion on the line joining the inion and the external auditory meatus. The coil position will be marked on the skin. 900 pulses will be delivered consecutively to each side with a frequency of 1 Hz and at an intensity of 90% of the resting motor threshold (RMT) for a total duration of 15 min for each cerebellar hemisphere. The RMT will be defined as the lowest stimulation intensity required to evoke a 50 μV potential in a target muscle. Constant coil position will be continuously monitored during the experiment. A similar protocol will be observed for the contralateral cerebellum. In addition, this group will have the following performed: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) test, Cerebellar-brain Inhibition (CBI) measurement, and Craniocervical Dystonia Questionnaire (CDQ-24) questionnaire to fill out.

Treatment:

Other: Craniocervical Dystonia Questionnaire (CDQ-24)

Other: Cerebellar-brain Inhibition (CBI)

Procedure: Botulinum toxin injections

Other: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)

Device: NeuroStar TMS therapy

Sham rTMS Stimulation

Sham Comparator group

Description:

Patients will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using sham NeuroStar TMS therapy system coil which produces discharge noise and vibration without stimulating the cerebral cortex. This technique has been suggested to provide more effective blinding compared to other methods use in previous controlled studies. In addition, this group will have the following performed: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) test, Cerebellar-brain Inhibition (CBI) measurement, and Craniocervical Dystonia Questionnaire (CDQ-24) questionnaire to fill out.

Treatment:

Other: Craniocervical Dystonia Questionnaire (CDQ-24)

Other: Cerebellar-brain Inhibition (CBI)

Procedure: Botulinum toxin injections

Other: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)

Device: Sham NeuroStar TMS therapy