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NCT01569607

Structurally Reorganizing Motor Cortex in Stroke Patients Through Hebbian-type Stimulation

Completed NA Results posted Last updated 16 January 2018
What this trial tests

NA trial testing Repetitive Transcranial Magnetic Stimulation (rTMS) in Stroke in 48 participants. Completed in 26 August 2016.

Timeline
8 March 2012
Primary endpoint
26 August 2016
26 August 2016

Quick facts

Lead sponsorCathrin Buetefisch
PhaseNA
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment48
Start date8 March 2012
Primary completion26 August 2016
Estimated completion26 August 2016
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Cathrin Buetefisch

Who can join

Adults 18 to 85, any sex, with Stroke. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Primary Motor Cortex (M1) Excitability Derived From Stimulus Response Curve Primary · Baseline, Post-Training 1 (1 Week), Post-Training 2 (4 Weeks)

Motor evoked potential (MEP) amplitudes were measured prior to treatment (baseline), one week after the treatment (post-training 1), and 4 weeks after treatment (post-training 2).The MEP is elicited by transcranial magnetic stimulation (TMS) at increased intensity. Its amplitude is measured from peak to peak and expressed in millivolts (mV). Measured MEP amplitudes were plotted against the intensity to create a stimulus response curve (SRC). Long-lasting increases in MEP amplitude indicate increases in motor cortex excitability and are associated with motor learning.

Baseline
GroupValue95% CI
Hebbian-type Stimulation4.68± 5.65
Sham Stimulation9.09± 11.28
Post-Training Week 1
GroupValue95% CI
Hebbian-type Stimulation5.01± 5.96
Sham Stimulation8.04± 9.28
Post-Training Week 4
GroupValue95% CI
Hebbian-type Stimulation2.66± 2.55
Sham Stimulation7.66± 10.67
Mean Time to Completion for Jebsen Hand Function Test (JTT) Secondary · Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

The JTT provides a standardized and objective evaluation of fine and gross motor hand function using simulated activities of daily living assessing the speed of performance. Total score is the sum of time taken for each sub-test, which were normalized to standard scores (also expressed in seconds).Total scores range from +1 to -1 where -1 indicates best function.

Baseline
GroupValue95% CI
Hebbian-type Stimulation.38± .23
Sham Stimulation.49± .21
Post-Training Week 1
GroupValue95% CI
Hebbian-type Stimulation.34± .26
Sham Stimulation.45± .20
Post-Training Week 4
GroupValue95% CI
Hebbian-type Stimulation.31± .26
Sham Stimulation.44± .21
Mean Peak Acceleration of Wrist Extension Movements Secondary · Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Mean peak acceleration was measured at baseline, one week after the treatment (post-training 1), and four weeks after the treatment (post-training 2). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface.

Baseline
GroupValue95% CI
Hebbian-type Stimulation.61± .48
Sham Stimulation.60± .32
Post-Training Week 1
GroupValue95% CI
Hebbian-type Stimulation.72± .32
Sham Stimulation.79± .49
Post-Training Week 4
GroupValue95% CI
Hebbian-type Stimulation.71± .32
Sham Stimulation.81± .47
Mean Reaction Time of Wrist Extension Movements Secondary · Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Subjects will be asked to perform 7 auditory-cued ballistic wrist extensions before and after motor training. Electromyographic (EMG) activity recorded during the ballistic wrist extensions will be used to measure reaction time. Reaction time is the length of time between the auditory cue and the onset of the movement-related EMG burst of the extensor carpi ulnaris muscle. A longer time indicated longer time to reaction.

Baseline
GroupValue95% CI
Hebbian-type Stimulation238.1± 77.40
Sham Stimulation257.14± 88.13
Post-Training Week 1
GroupValue95% CI
Hebbian-type Stimulation238.43± 36.38
Sham Stimulation224.59± 63.69
Post-Training Week 4
GroupValue95% CI
Hebbian-type Stimulation219.63± 67.55
Sham Stimulation225.35± 75.05
Mean Motor Activity Log (MAL) Score: Amount Subtest Secondary · Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Individuals are asked to rate amount of movement during 30 daily functional tasks. Items are scored on a 0 to 6-point ordinal scale as follows: 0 = The weaker arm was not used at all for that activity (never) 1 = Occasionally used weaker arm, but only very rarely (very rarely) 2= Sometimes used weaker arm, but did the activity most of the time with stronger arm (rarely) 3 = Used weaker arm about half as much as before the stroke (half pre-stroke) 4 = Used weaker arm almost as much as before the stroke (3/4 pre-stroke) 5 = The ability to use the weaker arm for that activity was as good as

Baseline
GroupValue95% CI
Hebbian-type Stimulation78.67± 23.16
Sham Stimulation78.00± 24.76
Post-Training Week 1
GroupValue95% CI
Hebbian-type Stimulation81.00± 23.63
Sham Stimulation79.00± 25.39
Post-Training Week 4
GroupValue95% CI
Hebbian-type Stimulation84.67± 23.21
Sham Stimulation77.33± 25.42
Mean Motor Activity Log (MAL): How Well Subtest Secondary · Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Individuals are asked to rate quality of movement during 30 daily functional tasks. Items are scored on a 6-point ordinal scale as follows: 0=The weaker arm was not used at all for that activity (never); 1=The weaker arm was moved during that activity, but was not helpful (very poor); 2=The weaker arm was of some use during the activity, but needed help from the stronger arm or moved very slowly or with difficulty (poor); 3=The weaker arm was used for the purpose indicated, but movements were slow or were made with only some effort (fair); 4=The movements made by the weaker arm were almost no

Baseline
GroupValue95% CI
Hebbian-type Stimulation3.41± .96
Sham Stimulation3.17± 1.18
Post-Training Week 1
GroupValue95% CI
Hebbian-type Stimulation3.64± 1.04
Sham Stimulation3.48± 1.23
Post-Training Week 4
GroupValue95% CI
Hebbian-type Stimulation3.92± .96
Sham Stimulation3.33± 1.21
Mean Wolf Motor Function Test (WMFT) Total Time Secondary · Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

The Wolf Motor Function Test (WMFT) is a quantitative index of upper extremity motor ability examinable through the use of timed and functional tasks. There are 15 timed tasks included with a time cap of 120 seconds. The max amount of time to completion is 1800 seconds if all tasks are failed. The time in seconds were summed across all the tasks to obtain the total duration. Values in the table represent the time taken in seconds to successfully complete all 15 tasks).

Baseline
GroupValue95% CI
Hebbian-type Stimulation120.84± 230.77
Sham Stimulation130.04± 153.06
Post-Training Week 1
GroupValue95% CI
Hebbian-type Stimulation91.31± 169.83
Sham Stimulation99.02± 131.79
Post-Training Week 4
GroupValue95% CI
Hebbian-type Stimulation99.81± 206.77
Sham Stimulation91.42± 118.77
Mean Wolf Motor Function Test Functional Ability (WMFT-FS) Scale Score Secondary · Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

The WMFT is a 17 item scale that quantifies upper extremity (UE) motor ability through timed and functional tasks. The items are rated on a 6-point scale.Total scores can range from 17 to 102. Lower scores indicate debilitating mobility (such as no or limited functionality), while higher score indicate greater mobility (such as slow movement and normal movement).

Baseline
GroupValue95% CI
Hebbian-type Stimulation4.07± .57
Sham Stimulation4.08± .72
Post-Training Week 1
GroupValue95% CI
Hebbian-type Stimulation4.31± .55
Sham Stimulation4.29± .62
Post-Training Week 4
GroupValue95% CI
Hebbian-type Stimulation4.34± .54
Sham Stimulation4.13± .54
Mean Wolf Motor Function Test (WMFT) Grip Strength Secondary · Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Participants attempt to grip the dynamometer with greatest grip strength possible. The test should be conducted 3 times with a 1-minute rest between trials. The mean of grip strength exerted (kg) on 3 trials is then calculated.

Baseline
GroupValue95% CI
Hebbian-type Stimulation20.80± 13.98
Sham Stimulation22.30± 12.72
Post-Training Week 1
GroupValue95% CI
Hebbian-type Stimulation22.30± 19.10
Sham Stimulation20.30± 9.04
Post-Training Week 4
GroupValue95% CI
Hebbian-type Stimulation20.90± 13.73
Sham Stimulation20.00± 11.57

Sponsor's own description

Stroke is a leading cause of morbidity in the United States but identification of treatment strategies to improve outcome is limited by the incomplete understanding of the mechanisms of recovery. Motor cortex (M1) reorganization plays a major-role in the recovery of motor deficits post-stroke; hence the importance for further development of rehabilitative strategies that utilize this potential for recovery. In Specific Aim 1, investigators will determine if repeated exposure to training combined with Hebbian-type M1 stimulation enhances functional M1 reorganization in lesioned M1 of stroke patients. In Specific Aim 2, investigators will determine if repeated exposure to training combined with Hebbian-type M1 stimulation enhances structural cortical reorganization in lesioned M1 of stroke patients and to explore whether these structural changes are related to the training induced functional cortical reorganization. The overall goal of this project is to determine the effect of Hebbian- type stimulation on both, functional and structural brain reorganization, thereby obtaining indirect evidence for the neuronal substrate underlying training related improvement and maintenance of motor function in stroke patients. This knowledge may have a substantial positive impact on treatment for stroke patients that may significantly improve recovery and could move the field of neuro-rehabilitation forward.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Hebbian-Type Primary Motor Cortex Stimulation: A Potential Treatment of Impaired Hand Function in Chronic Stroke Patients.
    Revill KP, Haut MW, Belagaje SR, Nahab F, et al · · 2020 · cited 15× · PMID 31976804 · DOI 10.1177/1545968319899911

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