rTMS and Retraining in Focal Hand Dystonia (DSS)

• ClinicalTrials.gov Identifier: NCT01738581
• Recruitment Status: Completed
• First Posted: November 30, 2012
• Results First Posted: June 28, 2016
• Last Update Posted: November 18, 2019
• Sponsor: University of Minnesota
• Information provided by (Responsible Party): University of Minnesota

Study Description

Brief Summary:

This study is exploring a new experimental procedure in dystonia called repetitive transcranial magnetic brain stimulation (TMS) combined with rehabilitation. The purpose of the study is to determine whether repetitive TMS is effective as a treatment to reduce symptoms in dystonia as demonstrated by improved motor performance.

Condition or disease	Intervention/treatment	Phase
Focal Dystonia	Device: Repetitive Transcranial Magnetic Stimulation; Behavioral: Sensorimotor Retraining; Behavioral: Non-specific Therapy	Phase 1; Phase 2

Detailed Description:

BACKGROUND: Though the etiology of focal hand dystonia (FHD) is uncertain, two primary factors implicated in the development of dystonic symptoms are excessive cortical excitability and impaired sensorimotor processing.

OBJECTIVE: The purpose of this study was to determine the functional efficacy and neural effects of a Dual intervention of rTMS and sensorimotor retraining. Our working hypothesis is: subjects receiving the combined intervention will (1) display significantly improved handwriting measures; (2) report significant improvement in daily functional ability; (3) display reduced hand cramping compared; and (4) demonstrate reduced corticospinal excitability after the Dual intervention when compared to the rTMS+ stretching and massage (Sham) intervention.

METHODS: A randomized, single-subject, multiple baseline design with crossover is used for this study that will examine ten subjects with FHD with two interventions: five days of low-frequency 1 Hz rTMS + sensorimotor retraining (Dual intervention) vs. rTMS + stretching and massage (Sham). The rTMS is applied to the premotor cortex at 1 Hz at 90% resting motor threshold for 1200 pulses. For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effectiveness of rTMS and Retraining in the Treatment of Focal Hand Dystonia
• Study Start Date: November 2011
• Actual Primary Completion Date: June 2015
• Actual Study Completion Date: June 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: rTMS + SMR, then rTMS + CTL; First phase of treatment: Repetitive transcranial magnetic stimulation (rTMS) and sensorimotor retraining (SMR). Second phase of treatment: rTMS and control treatment (CTL) (CTL therapy consisted of non-specific therapy that includes stretching, massage, range of motion).	Device: Repetitive Transcranial Magnetic Stimulation; Applied to the premotor cortex at 1 Hz at 90% resting motor threshold for 1200 pulses.; Other Names: Magstim stimulator (Magstim Co. LTD, Whitland,UK); Neuromodulation; Behavioral: Sensorimotor Retraining; For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed; Other Names: Learning-based Sensorimotor Training program,; Sensory and motor Retraining; Behavioral: Non-specific Therapy; A non-specific massage and stretching program directed to the hand, wrist and forearm; Other Names: Massage; Stretching
Experimental: rTMS + CTL, then rTMS + SMR; First phase of treatment: Repetitive transcranial magnetic stimulation (rTMS) with non-specific therapy that includes stretching, massage, range of motion. Second phase of treatment: rTMS and sensorimotor retraining (SMR).	Device: Repetitive Transcranial Magnetic Stimulation; Applied to the premotor cortex at 1 Hz at 90% resting motor threshold for 1200 pulses.; Other Names: Magstim stimulator (Magstim Co. LTD, Whitland,UK); Neuromodulation; Behavioral: Sensorimotor Retraining; For sensorimotor retraining, a subset of the Learning-based Sensorimotor Training program was followed; Other Names: Learning-based Sensorimotor Training program,; Sensory and motor Retraining; Behavioral: Non-specific Therapy; A non-specific massage and stretching program directed to the hand, wrist and forearm; Other Names: Massage; Stretching

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Global Rating of Change at Posttest (Day 5) [ Time Frame: Baseline and Posttest ]
   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).

Secondary Outcome Measures :

1. Change From Baseline in Arm Dystonia Disability Scale at Posttest (Day 5) [ Time Frame: Baseline and Posttest ]
   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.
2. Change From Baseline in Sensation at Posttest (Day 5) [ Time Frame: Baseline and Posttest ]
   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).
3. Change From Baseline in Cortical Silent Period at Posttest (Day 5) [ Time Frame: Baseline and Posttest ]

   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

4. Change From Baseline for Pressure During Hand Writing at Posttest (Day 5) [ Time Frame: Baseline and Posttest ]
   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.
5. Change From Baseline for Physician Rated Impairment at Posttest (Day 5) [ Time Frame: Baseline and Posttest ]
   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.
6. Change From Baseline in Physical Function at Posttest (Day 5) [ Time Frame: Baseline and Posttest ]
   Participants completed the full SF-36 assessment with subsection of interest: "physical functioning".

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Greater than 18 years of age
• Symptoms of focal hand dystonia or writer's cramp

Exclusion Criteria:

• History of seizure or other neurologic disorder

Contacts and Locations

Locations

United States, Minnesota

University of Minnesota, Program in Physical Therapy

Minneapolis, Minnesota, United States, 55414

Program in Physical Therapy, University of Minnesota

Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

University of Minnesota

Investigators

• Principal Investigator: Teresa J Kimberley, PhD, PT; University of Minnesota, Program in Physical Therapy

More Information

Publications of Results:

Kimberley TJ, Schmidt RL, Chen M, Dykstra DD, Buetefisch CM. Mixed effectiveness of rTMS and retraining in the treatment of focal hand dystonia. Front Hum Neurosci. 2015 Jul 9;9:385. doi: 10.3389/fnhum.2015.00385. eCollection 2015.

Other Publications:

Byl NN, Nagajaran S, McKenzie AL. Effect of sensory discrimination training on structure and function in patients with focal hand dystonia: a case series. Arch Phys Med Rehabil. 2003 Oct;84(10):1505-14.

Kimberley TJ, Borich MR, Arora S, Siebner HR. Multiple sessions of low-frequency repetitive transcranial magnetic stimulation in focal hand dystonia: clinical and physiological effects. Restor Neurol Neurosci. 2013;31(5):533-42. doi: 10.3233/RNN-120259.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT01738581
• Other Study ID Numbers: 0608M91226-2
• First Posted: November 30, 2012
• Results First Posted: June 28, 2016
• Last Update Posted: November 18, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by University of Minnesota:

focal hand dystonia (FHD); repetitive transcranial magnetic stimulation (rTMS); sensorimotor retraining

Additional relevant MeSH terms:

Dystonia; Dystonic Disorders; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Movement Disorders; Central Nervous System Diseases