Dystonia Treatment With Injections Supplemented By Transcranial Magnetic Stimulation

Not Applicable

Completed

Conditions: Cervical Dystonia

Interventions: Device: rTMS

Registration Number: NCT04916444

Lead Sponsor: University of Florida

Brief Summary: We applied 16 sessions of rTMS over 4 consecutive days for adult patients suffering from cervical dystonia who received botulinum toxin (BoNT) injections on a regular basis. The TMS protocol took place 9 weeks following their last BoNT injection. The primary outcome measure was improvement in cervical dystonia as measured by the TWSTRS scale. The secondary outcome measures included mood, cognition, and gait measures.

Detailed Description: This was a crossover study design in which patients were randomized to active or sham stimulation during session 1 (S1) and then crossed over to the condition they were not randomized to at first during session 2 (S1). Patients who were receiving BoNT injections for cervical dystonia on a regular basis but only noted benefit from BoNT for 9 weeks or less were eligible to participate. The total study protocol took place over 24 weeks. During week 1, patients had their regularly scheduled botox injections. During week 9, patients underwent either active or sham rTMS, as detailed below. They had outcome measures obtained at week 9 (S1:T0; baseline/pre-TMS), week 10 (S1:T1; post-TMS), and week 12 (S1:T2; 2 weeks post-TMS). At week 12, they underwent their regularly scheduled BoNT injections. During week 21, patients underwent either active or sham rTMS, whichever condition they were not randomized into during the first session. They then had outcome measures obtained at week 21 (S2:T0; baseline/pre-TMS), week 22 (S2:T1; post-TMS), and week 24 (S2:T2; 2 weeks post-TMS).

The neurostimulation protocol was as follows: The dPMC target was defined as 1 cm medial and 2 cm anterior to the site of RMT acquisition. The rTMS protocol was as follows: each session consisted of 1-Hz rTMS over the dPMC for 30 minutes (1800 pulses) at 90% of the RMT. Patients received 4 sessions per day for 4 consecutive days with a 10-minute break between each session. The daily duration of the rTMS protocol, including breaks, lasted approximately 160 minutes.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 5

Inclusion Criteria

patients 18-85 years of age who receive regular botulinum toxin (BoNT) scheduled every 12 weeks, on stable optimized doses but with reported benefits lasting ≤ 9 weeks for 2 consecutive cycles. Patents followed at our center routinely fill out a self-reported form to document the duration of benefits perceived with BoNT therapy. Participants will be allowed to continue oral medications that they are taking for dystonia concurrently but will not be allowed to change their concurrent medication regimen throughout the duration of the study.

Exclusion Criteria

Presence of metallic objects or neurostimulators in the brain
Pregnancy
History of active seizures or epilepsy
Patients with severe scoliosis or other gait impairment that will preclude them from participating in gait evaluation.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Active rTMS	rTMS	Active rTMS will use a figure of eight TMS coil that will deliver real neurostimulation pulses to the patients.
Sham rTMS	rTMS	Sham rTMS will use a sham figure of eight TMS coil that sounds and looks like a real rTMS coil, except no neurostimulation is being delivered to the patient.

Primary Outcome Measures

Name	Time	Method
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)	Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24)	This is an objective scale evaluating patients on a variety of features including maximal excursion, duration, effects of sensory trick, shoulder elevation, range of motion, and time. Scores range from 0 to 85 where a higher score indicates more severity.

Secondary Outcome Measures

Name	Time	Method
Beck Depression Inventory (BDI)	Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24)	This is a 21-question survey evaluating depression in patients on a 0 to 3 scale, with a minimum score of 0 and maximum score 63, and higher score indicating a higher level of depression.
Trail-Making Test: Part A	Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24)	Patients are instructed to connect circles in ascending numerical order and are scored on how quickly they are able to complete the task. A longer amount of time indicates more severe cognitive impairment (in general, more than 78 seconds to complete Part A is considered impaired).
Trail-Making Test: Part B	Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24)	Patients are instructed to connect circles in ascending numerical order and are scored on how quickly they are able to complete the task. A longer amount of time indicates more severe cognitive impairment (in general, more than 273 seconds to complete Part B is considered impaired).
Wisconsin Card Sorting Task (WCST) - %Total Errors	Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24)	The Wisconsin Card Sorting Test is a test of rule-learning and conceptual flexibility. The participant is required to learn to sort a series of cards according to one of three principles (color, form or number) based on response feedback. This measure is computed by calculating the ration of total errors to trials administered and multiplied by 100.
Wisconsin Card Sorting Task (WCST) - %Perseverative Errors	Before rTMS (Session 1: Week 9, Session 2: Week 21), Immediately after rTMS (Session 1: Week 10, Session 2: Week 22), 2 weeks after rTMS (Session 1: Week 12, Session 2: Week 24)	The Wisconsin Card Sorting Test is a test of rule-learning and conceptual flexibility. The participant is required to learn to sort a series of cards according to one of three principles (color, form or number) based on response feedback. This measure reflects the "density" of perseverative errors in relation to the overall test performance. It is computed by calculating the ration of total errors to trials administered and multiplied by 100.