Clinical trial NCT04916444: Dystonia Treatment With Injections Supplemented By Transcranial Magnetic Stimulation
Official title: Dystonia Treatment With Injections Supplemented By Transcranial Magnetic Stimulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cervical Dystonia
Keywords: rTMS
cervical dystonia
botulinum toxin
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Dystonia Medical Research Foundation
First posted: 2021-06-07
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients were randomized to one of two conditions during session 1: active or sham rTMS. During session 2, patients underwent whichever condition they did not undergo in session 1.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
timeFrame: 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)
Secondary outcomes:
measure: Beck Depression Inventory (BDI)
timeFrame: 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)
measure: Trail-Making Test: Part A
timeFrame: 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)
measure: Trail-Making Test: Part B
timeFrame: 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)
measure: Wisconsin Card Sorting Task (WCST) - %Total Errors
timeFrame: 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)
measure: Wisconsin Card Sorting Task (WCST) - %Perseverative Errors
timeFrame: 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)
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida Health Norman Fixel Institute for Neurological Diseases
state: Florida
Study officials:
affiliation: University of Florida
name: Jun Yu, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: