Trial Outcomes & Findings for rTMS and Retraining in Focal Hand Dystonia (NCT NCT01738581)

NCT ID: NCT01738581

Last Updated: 2019-11-18

Results Overview

Symptom severity was assessed using the global rating of change (GROC). For the GROC, participants were asked to identify between one to three functions most impacted by focal hand dystonia. At posttest 1 they were then asked to select a rating of perceived change that represented the level of function compared to baseline. Perceived change consisted of a ±7 point Likert scale (+7= a very great deal better, 0= no change, -7= a very great deal worse).

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 9 participants
• Primary outcome timeframe: Baseline and Posttest
• Results posted on: 2019-11-18

Participant Flow

Participant milestones

Measure	rTMS + SMR, Then rTMS + CTL Repetitive transcranial magnetic stimulation and sensorimotor retraining Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed	rTMS + CTL, Then rTMS + SMR Repetitive transcranial magnetic stimulation (rTMS) with non-specific therapy that includes stretching, massage, range of motion Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses.
Overall Study STARTED	5	4
Overall Study COMPLETED	4	4
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	rTMS + SMR, Then rTMS + CTL Repetitive transcranial magnetic stimulation and sensorimotor retraining Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed	rTMS + CTL, Then rTMS + SMR Repetitive transcranial magnetic stimulation (rTMS) with non-specific therapy that includes stretching, massage, range of motion Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses.
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

rTMS and Retraining in Focal Hand Dystonia

Baseline characteristics by cohort

Measure	rTMS + Sensorimotor Retraining, rTMS + CTL n=5 Participants Repetitive transcranial magnetic (rTMS) stimulation and sensorimotor retraining for the first phase, then rTMS with control therapy (CTL). CTL therapy was non-specific therapy that includes stretching, massage, range of motion. Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed	rTMS + CTL, rTMS + Sensorimotor Retraining n=4 Participants Repetitive transcranial magnetic stimulation (rTMS) with control therapy (CTL). CTL therapy was non-specific therapy that includes stretching, massage, range of motion for the first phase, then rTMS with sensorimotor retraining. Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses.	Total n=9 Participants Total of all reporting groups
Age, Continuous	48 years STANDARD_DEVIATION 13.55359731 • n=5 Participants	44 years STANDARD_DEVIATION 6.751543034 • n=7 Participants	46 years STANDARD_DEVIATION 10.64320336 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Posttest

Population: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.

Symptom severity was assessed using the global rating of change (GROC). For the GROC, participants were asked to identify between one to three functions most impacted by focal hand dystonia. At posttest 1 they were then asked to select a rating of perceived change that represented the level of function compared to baseline. Perceived change consisted of a ±7 point Likert scale (+7= a very great deal better, 0= no change, -7= a very great deal worse).

Outcome measures

Measure	rTMS With Sensorimotor Retraining n=5 Participants Repetitive transcranial magnetic stimulation and sensorimotor retraining Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed	rTMS With Control Therapy n=4 Participants Repetitive transcranial magnetic stimulation (rTMS) with non-specific therapy that includes stretching, massage, range of motion Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses.
Change From Baseline in Global Rating of Change at Posttest (Day 5)	1.3 units on a scale Interval 0.0 to 3.0	1.2 units on a scale Interval -4.0 to 3.0

SECONDARY outcome

Timeframe: Baseline and Posttest

Population: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.

The Arm Dystonia Disability Scale (ADDS) is a survey where participants rate task difficulty for activities such as writing, handling utensils, and buttoning on a scale of 1-4 (1 = no difficulty ,4 = not able or marked difficulty). This is a subjective assessment of impairment due to focal hand dystonia. Scores are determined using an equation: total points scored, divided by the maximum possible (23), multiplied by the quotient by 90 and subtract from 90%. Scores range from 0%-90% with higher scores indicating more function.

Outcome measures

Measure	rTMS With Sensorimotor Retraining n=5 Participants Repetitive transcranial magnetic stimulation and sensorimotor retraining Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed	rTMS With Control Therapy n=4 Participants Repetitive transcranial magnetic stimulation (rTMS) with non-specific therapy that includes stretching, massage, range of motion Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses.
Change From Baseline in Arm Dystonia Disability Scale at Posttest (Day 5)	71.98 percentage of function Standard Deviation 7.031320694	71.42 percentage of function Standard Deviation 8.464086657

SECONDARY outcome

Timeframe: Baseline and Posttest

Population: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.

Examinations included two point discrimination. Two-point discrimination threshold was completed using a Disk-Criminator™. Participants were asked to reply "one" or "two" after each presentation. Static and dynamic stimuli were presented to the index and ring fingers bilaterally, meaning it was presented as a static stimuli or it was slowly swept across the skin (dynamic).

Outcome measures

Measure	rTMS With Sensorimotor Retraining n=5 Participants Repetitive transcranial magnetic stimulation and sensorimotor retraining Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed	rTMS With Control Therapy n=4 Participants Repetitive transcranial magnetic stimulation (rTMS) with non-specific therapy that includes stretching, massage, range of motion Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses.
Change From Baseline in Sensation at Posttest (Day 5) Improvement	3 Participants	2 Participants
Change From Baseline in Sensation at Posttest (Day 5) No Change	2 Participants	1 Participants
Change From Baseline in Sensation at Posttest (Day 5) Worsening	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and Posttest

Population: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.

Cortical silent period (CSP) testing was completed during an isometric contraction of the target muscle whereby the motor evoked potential is followed by a short duration of electromyographic quiescence. The maximal voluntary contraction for finger abduction was recorded using a custom strain gauge placed around the index finger. Real-time visual feedback was given on a laptop screen to project the force produced by the participant and 20% of the maximum of three trials was calculated and displayed on a target line. For the CSP, participants were asked to contract until the target line was met, then a single transcranial magnetic stimulation pulse was delivered to the motor cortex. Ten trials were collected with a short rest period to prevent fatigue.

CSP duration was calculated in milliseconds (ms). CSP EMG data were first rectified, and then a 10-ms moving average calculation was applied to the data. The onset of the CSP was set as the time point of the delivery of the TM

Outcome measures

Measure	rTMS With Sensorimotor Retraining n=5 Participants Repetitive transcranial magnetic stimulation and sensorimotor retraining Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed	rTMS With Control Therapy n=4 Participants Repetitive transcranial magnetic stimulation (rTMS) with non-specific therapy that includes stretching, massage, range of motion Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses.
Change From Baseline in Cortical Silent Period at Posttest (Day 5) Improvement	2 Participants	1 Participants
Change From Baseline in Cortical Silent Period at Posttest (Day 5) No Change	2 Participants	1 Participants
Change From Baseline in Cortical Silent Period at Posttest (Day 5) Worsening	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline and Posttest

Population: One participant that did not display symptoms affecting handwriting and did not participate in the handwriting analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.

Digitized handwriting was assessed using a computerized tablet (WACOM Co., Ltd., japan) with MovAlyzeR® (Neuroscript LLC, Tempe, AZ) hardware and software. Participants used a custom modified digitized pen (Kiko Software, Netherlands) to write in a self-selected pace and style on the tablet with real-time visual feedback. Writing tasks included "My country tis of thee" at a self-selected pace, repeated eight times. Data were sampled at 215 Hz (resolution: 5080 lpi, accuracy: ±0.01 pressure range: 0-800 g). Writing samples were segmented by points of minimal velocity into single strokes for analysis. Pressure for each stroke was automatically calculated within the software.

Outcome measures

Measure	rTMS With Sensorimotor Retraining n=5 Participants Repetitive transcranial magnetic stimulation and sensorimotor retraining Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed	rTMS With Control Therapy n=3 Participants Repetitive transcranial magnetic stimulation (rTMS) with non-specific therapy that includes stretching, massage, range of motion Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses.
Change From Baseline for Pressure During Hand Writing at Posttest (Day 5) Improvement	2 Participants	2 Participants
Change From Baseline for Pressure During Hand Writing at Posttest (Day 5) No Change	3 Participants	1 Participants
Change From Baseline for Pressure During Hand Writing at Posttest (Day 5) Worsening	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Posttest

Population: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.

Video recordings were made as participants wrote on a pad of paper with pen. Participants were asked to draw a series of 10 loops across the pad of paper followed by "The dog is barking" and their signature, each repeated four times. A physician blinded to participant allocation rated recordings. Scoring criteria were adapted from a standardized writer's cramp rating scale (WCRS) (Wissel et al., 1996), rating pathological flexion or extension at the wrist, fingers and elbow, presence of tremor, dystonic posture, writing speed and latency of dystonic symptoms. Final scores are expressed as a rating listed as a movement score.

Outcome measures

Measure	rTMS With Sensorimotor Retraining n=5 Participants Repetitive transcranial magnetic stimulation and sensorimotor retraining Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed	rTMS With Control Therapy n=4 Participants Repetitive transcranial magnetic stimulation (rTMS) with non-specific therapy that includes stretching, massage, range of motion Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses.
Change From Baseline for Physician Rated Impairment at Posttest (Day 5) Improvement	2 Participants	0 Participants
Change From Baseline for Physician Rated Impairment at Posttest (Day 5) No Change	3 Participants	3 Participants
Change From Baseline for Physician Rated Impairment at Posttest (Day 5) Worsening	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and Posttest

Population: All participants who completed the first phase were included in the analysis. Data were only analyzed in the first intervention period of the study because there was a lack of a washout effect between periods. This lack of washout made data from the second intervention period unreliable.

Participants completed the full SF-36 assessment with subsection of interest: "physical functioning".

Outcome measures

Measure	rTMS With Sensorimotor Retraining n=5 Participants Repetitive transcranial magnetic stimulation and sensorimotor retraining Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed	rTMS With Control Therapy n=4 Participants Repetitive transcranial magnetic stimulation (rTMS) with non-specific therapy that includes stretching, massage, range of motion Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses.
Change From Baseline in Physical Function at Posttest (Day 5) Improvement	1 Participants	0 Participants
Change From Baseline in Physical Function at Posttest (Day 5) No Change	4 Participants	2 Participants
Change From Baseline in Physical Function at Posttest (Day 5) Worsening	0 Participants	2 Participants

Adverse Events

rTMS With Sensorimotor Retraining, Then rTMS With CTL

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

rTMS With CTL, Then rTMS With Sensorimotor Retrain

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	rTMS With Sensorimotor Retraining, Then rTMS With CTL n=5 participants at risk Repetitive transcranial magnetic stimulation (rTMS) and sensorimotor retraining for first phase, then rTMS with control (CTL) therapy. Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed	rTMS With CTL, Then rTMS With Sensorimotor Retrain n=4 participants at risk Repetitive transcranial magnetic stimulation (rTMS) with control (CTL) non-specific therapy that includes stretching, massage, range of motion for first phase, then rTMS with sensorimotor retraining for second phase. Repetitive Transcranial Magnetic Stimulation (Magstim): Applied to the premotor cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. Sensorimotor Retraining: For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed
Nervous system disorders Headache	0.00% 0/5 • Before and after each session of the intervention phase Participants were evaluated per-sequence due to the lack of washout effect. Each participant was asked to identify if an event occurred immediately after and the beginning of each session throughout the study. A list of common side-effects was presented to each participant to report 'yes or no' to each side effect.	50.0% 2/4 • Number of events 8 • Before and after each session of the intervention phase Participants were evaluated per-sequence due to the lack of washout effect. Each participant was asked to identify if an event occurred immediately after and the beginning of each session throughout the study. A list of common side-effects was presented to each participant to report 'yes or no' to each side effect.
Musculoskeletal and connective tissue disorders Neck Pain	0.00% 0/5 • Before and after each session of the intervention phase Participants were evaluated per-sequence due to the lack of washout effect. Each participant was asked to identify if an event occurred immediately after and the beginning of each session throughout the study. A list of common side-effects was presented to each participant to report 'yes or no' to each side effect.	50.0% 2/4 • Number of events 2 • Before and after each session of the intervention phase Participants were evaluated per-sequence due to the lack of washout effect. Each participant was asked to identify if an event occurred immediately after and the beginning of each session throughout the study. A list of common side-effects was presented to each participant to report 'yes or no' to each side effect.
Psychiatric disorders Abnormal Sleep Pattern	20.0% 1/5 • Number of events 2 • Before and after each session of the intervention phase Participants were evaluated per-sequence due to the lack of washout effect. Each participant was asked to identify if an event occurred immediately after and the beginning of each session throughout the study. A list of common side-effects was presented to each participant to report 'yes or no' to each side effect.	0.00% 0/4 • Before and after each session of the intervention phase Participants were evaluated per-sequence due to the lack of washout effect. Each participant was asked to identify if an event occurred immediately after and the beginning of each session throughout the study. A list of common side-effects was presented to each participant to report 'yes or no' to each side effect.
Nervous system disorders Decreased balance	40.0% 2/5 • Number of events 2 • Before and after each session of the intervention phase Participants were evaluated per-sequence due to the lack of washout effect. Each participant was asked to identify if an event occurred immediately after and the beginning of each session throughout the study. A list of common side-effects was presented to each participant to report 'yes or no' to each side effect.	0.00% 0/4 • Before and after each session of the intervention phase Participants were evaluated per-sequence due to the lack of washout effect. Each participant was asked to identify if an event occurred immediately after and the beginning of each session throughout the study. A list of common side-effects was presented to each participant to report 'yes or no' to each side effect.
Psychiatric disorders Mood change	20.0% 1/5 • Number of events 1 • Before and after each session of the intervention phase Participants were evaluated per-sequence due to the lack of washout effect. Each participant was asked to identify if an event occurred immediately after and the beginning of each session throughout the study. A list of common side-effects was presented to each participant to report 'yes or no' to each side effect.	0.00% 0/4 • Before and after each session of the intervention phase Participants were evaluated per-sequence due to the lack of washout effect. Each participant was asked to identify if an event occurred immediately after and the beginning of each session throughout the study. A list of common side-effects was presented to each participant to report 'yes or no' to each side effect.

Additional Information

Dr. Teresa Kimberley

University of Minnesota

Phone: 612-626-4096

Email: tjk@umn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place