Trial Outcomes & Findings for Structurally Reorganizing Motor Cortex in Stroke Patients Through Hebbian-type Stimulation (NCT NCT01569607)

NCT ID: NCT01569607

Last Updated: 2018-01-16

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 48 participants
• Primary outcome timeframe: Baseline, Post-Training 1 (1 Week), Post-Training 2 (4 Weeks)
• Results posted on: 2018-01-16

Participant Flow

Participants were recruited between March 2012 and August 2016.

Participants completed the eligibility phase prior to being randomized to a study arm. Of the 48 participants that provided consent, 22 were eligible for participation and were randomized to an intervention.

Participant milestones

Measure	Hebbian-type Stimulation Participants were randomized to receive motor training with Hebbian-type stimulation. Repetitive Transcranial Magnetic Stimulation (rTMS): Training sessions for 5 days in a row	Sham Stimulation Participants were randomized to receive sham stimulation. Sham stimulation: Sham stimulation
Overall Study STARTED	11	11
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Hebbian-type Stimulation n=11 Participants Participants were randomized to receive motor training with Hebbian-type stimulation. Repetitive Transcranial Magnetic Stimulation (rTMS): Training sessions for 5 days in a row	Sham Stimulation n=11 Participants Participants were randomized to receive sham stimulation. Sham stimulation: Sham stimulation	Total n=22 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=11 Participants	0 Participants n=11 Participants	0 Participants n=22 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=11 Participants	6 Participants n=11 Participants	13 Participants n=22 Participants
Age, Categorical >=65 years	4 Participants n=11 Participants	5 Participants n=11 Participants	9 Participants n=22 Participants
Sex: Female, Male Female	6 Participants n=11 Participants	5 Participants n=11 Participants	11 Participants n=22 Participants
Sex: Female, Male Male	5 Participants n=11 Participants	6 Participants n=11 Participants	11 Participants n=22 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	11 Participants n=11 Participants	11 Participants n=11 Participants	22 Participants n=22 Participants

PRIMARY outcome

Timeframe: Baseline, Post-Training 1 (1 Week), Post-Training 2 (4 Weeks)

Population: Analysis was conducted for participants that completed all study procedures.

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.

Outcome measures

Measure	Hebbian-type Stimulation n=10 Participants Participants were randomized to receive motor training with Hebbian-type stimulation. Repetitive Transcranial Magnetic Stimulation (rTMS): Training sessions for 5 days in a row	Sham Stimulation n=10 Participants Participants were randomized to receive sham stimulation. Sham stimulation: Sham stimulation
Primary Motor Cortex (M1) Excitability Derived From Stimulus Response Curve Baseline	4.68 millivolts Standard Deviation 5.65	9.09 millivolts Standard Deviation 11.28
Primary Motor Cortex (M1) Excitability Derived From Stimulus Response Curve Post-Training Week 1	5.01 millivolts Standard Deviation 5.96	8.04 millivolts Standard Deviation 9.28
Primary Motor Cortex (M1) Excitability Derived From Stimulus Response Curve Post-Training Week 4	2.66 millivolts Standard Deviation 2.55	7.66 millivolts Standard Deviation 10.67

SECONDARY outcome

Timeframe: Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Population: Analysis was conducted for participants that completed all study procedures.

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.

Outcome measures

Measure	Hebbian-type Stimulation n=10 Participants Participants were randomized to receive motor training with Hebbian-type stimulation. Repetitive Transcranial Magnetic Stimulation (rTMS): Training sessions for 5 days in a row	Sham Stimulation n=10 Participants Participants were randomized to receive sham stimulation. Sham stimulation: Sham stimulation
Mean Time to Completion for Jebsen Hand Function Test (JTT) Baseline	.38 units on a scale Standard Deviation .23	.49 units on a scale Standard Deviation .21
Mean Time to Completion for Jebsen Hand Function Test (JTT) Post-Training Week 1	.34 units on a scale Standard Deviation .26	.45 units on a scale Standard Deviation .20
Mean Time to Completion for Jebsen Hand Function Test (JTT) Post-Training Week 4	.31 units on a scale Standard Deviation .26	.44 units on a scale Standard Deviation .21

SECONDARY outcome

Timeframe: Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Population: Three participants from both arms were removed from the data analysis due to errors in data collection yielding uninterpretable results.

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.

Outcome measures

Measure	Hebbian-type Stimulation n=7 Participants Participants were randomized to receive motor training with Hebbian-type stimulation. Repetitive Transcranial Magnetic Stimulation (rTMS): Training sessions for 5 days in a row	Sham Stimulation n=7 Participants Participants were randomized to receive sham stimulation. Sham stimulation: Sham stimulation
Mean Peak Acceleration of Wrist Extension Movements Baseline	.61 g Standard Deviation .48	.60 g Standard Deviation .32
Mean Peak Acceleration of Wrist Extension Movements Post-Training Week 1	.72 g Standard Deviation .32	.79 g Standard Deviation .49
Mean Peak Acceleration of Wrist Extension Movements Post-Training Week 4	.71 g Standard Deviation .32	.81 g Standard Deviation .47

SECONDARY outcome

Timeframe: Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Population: Three participants from both arms were removed from the data analysis due to errors in data collection yielding uninterpretable results.

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.

Outcome measures

Measure	Hebbian-type Stimulation n=7 Participants Participants were randomized to receive motor training with Hebbian-type stimulation. Repetitive Transcranial Magnetic Stimulation (rTMS): Training sessions for 5 days in a row	Sham Stimulation n=7 Participants Participants were randomized to receive sham stimulation. Sham stimulation: Sham stimulation
Mean Reaction Time of Wrist Extension Movements Baseline	238.1 milliseconds Standard Deviation 77.40	257.14 milliseconds Standard Deviation 88.13
Mean Reaction Time of Wrist Extension Movements Post-Training Week 1	238.43 milliseconds Standard Deviation 36.38	224.59 milliseconds Standard Deviation 63.69
Mean Reaction Time of Wrist Extension Movements Post-Training Week 4	219.63 milliseconds Standard Deviation 67.55	225.35 milliseconds Standard Deviation 75.05

SECONDARY outcome

Timeframe: Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Population: Analysis was conducted for participants that completed all study procedures.

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 before the stroke (normal)

Total scores range from 0 to 140; 0 indicating the least movement 140 indicating the most movement. The scores were converted into percentage scores where higher percent score indicate more movement and lower percent score less movement.

Outcome measures

Measure	Hebbian-type Stimulation n=10 Participants Participants were randomized to receive motor training with Hebbian-type stimulation. Repetitive Transcranial Magnetic Stimulation (rTMS): Training sessions for 5 days in a row	Sham Stimulation n=10 Participants Participants were randomized to receive sham stimulation. Sham stimulation: Sham stimulation
Mean Motor Activity Log (MAL) Score: Amount Subtest Baseline	78.67 units on a scale Standard Deviation 23.16	78.00 units on a scale Standard Deviation 24.76
Mean Motor Activity Log (MAL) Score: Amount Subtest Post-Training Week 1	81.00 units on a scale Standard Deviation 23.63	79.00 units on a scale Standard Deviation 25.39
Mean Motor Activity Log (MAL) Score: Amount Subtest Post-Training Week 4	84.67 units on a scale Standard Deviation 23.21	77.33 units on a scale Standard Deviation 25.42

SECONDARY outcome

Timeframe: Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Population: Analysis was conducted for participants that completed all study procedures.

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 normal, but were not quite as fast or accurate as normal (almost normal); 5=The ability to use the weaker arm for that activity was as good as before the stroke (normal)

Total scores range from 0 to 140; 0 indicating the least movement and 140 indicating the most movement.

Outcome measures

Measure	Hebbian-type Stimulation n=10 Participants Participants were randomized to receive motor training with Hebbian-type stimulation. Repetitive Transcranial Magnetic Stimulation (rTMS): Training sessions for 5 days in a row	Sham Stimulation n=10 Participants Participants were randomized to receive sham stimulation. Sham stimulation: Sham stimulation
Mean Motor Activity Log (MAL): How Well Subtest Baseline	3.41 units on a scale Standard Deviation .96	3.17 units on a scale Standard Deviation 1.18
Mean Motor Activity Log (MAL): How Well Subtest Post-Training Week 1	3.64 units on a scale Standard Deviation 1.04	3.48 units on a scale Standard Deviation 1.23
Mean Motor Activity Log (MAL): How Well Subtest Post-Training Week 4	3.92 units on a scale Standard Deviation .96	3.33 units on a scale Standard Deviation 1.21

SECONDARY outcome

Timeframe: Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Population: Analysis was conducted for participants that completed all study procedures.

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).

Outcome measures

Measure	Hebbian-type Stimulation n=10 Participants Participants were randomized to receive motor training with Hebbian-type stimulation. Repetitive Transcranial Magnetic Stimulation (rTMS): Training sessions for 5 days in a row	Sham Stimulation n=10 Participants Participants were randomized to receive sham stimulation. Sham stimulation: Sham stimulation
Mean Wolf Motor Function Test (WMFT) Total Time Post-Training Week 1	91.31 seconds Standard Deviation 169.83	99.02 seconds Standard Deviation 131.79
Mean Wolf Motor Function Test (WMFT) Total Time Post-Training Week 4	99.81 seconds Standard Deviation 206.77	91.42 seconds Standard Deviation 118.77
Mean Wolf Motor Function Test (WMFT) Total Time Baseline	120.84 seconds Standard Deviation 230.77	130.04 seconds Standard Deviation 153.06

SECONDARY outcome

Timeframe: Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Population: One participant from both arms was removed from the data analysis due to errors in data collection yielding uninterpretable results.

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).

Outcome measures

Measure	Hebbian-type Stimulation n=9 Participants Participants were randomized to receive motor training with Hebbian-type stimulation. Repetitive Transcranial Magnetic Stimulation (rTMS): Training sessions for 5 days in a row	Sham Stimulation n=9 Participants Participants were randomized to receive sham stimulation. Sham stimulation: Sham stimulation
Mean Wolf Motor Function Test Functional Ability (WMFT-FS) Scale Score Post-Training Week 4	4.34 units on a scale Standard Deviation .54	4.13 units on a scale Standard Deviation .54
Mean Wolf Motor Function Test Functional Ability (WMFT-FS) Scale Score Post-Training Week 1	4.31 units on a scale Standard Deviation .55	4.29 units on a scale Standard Deviation .62
Mean Wolf Motor Function Test Functional Ability (WMFT-FS) Scale Score Baseline	4.07 units on a scale Standard Deviation .57	4.08 units on a scale Standard Deviation .72

SECONDARY outcome

Timeframe: Baseline, Post-Training (1 Week), Post-Training (4 Weeks)

Population: Analysis was conducted for participants that completed all study procedures.

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.

Outcome measures

Measure	Hebbian-type Stimulation n=10 Participants Participants were randomized to receive motor training with Hebbian-type stimulation. Repetitive Transcranial Magnetic Stimulation (rTMS): Training sessions for 5 days in a row	Sham Stimulation n=10 Participants Participants were randomized to receive sham stimulation. Sham stimulation: Sham stimulation
Mean Wolf Motor Function Test (WMFT) Grip Strength Baseline	20.80 kilograms Standard Deviation 13.98	22.30 kilograms Standard Deviation 12.72
Mean Wolf Motor Function Test (WMFT) Grip Strength Post-Training Week 1	22.30 kilograms Standard Deviation 19.10	20.30 kilograms Standard Deviation 9.04
Mean Wolf Motor Function Test (WMFT) Grip Strength Post-Training Week 4	20.90 kilograms Standard Deviation 13.73	20.00 kilograms Standard Deviation 11.57

Adverse Events

Hebbian-type Stimulation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sham Stimulation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Cathrin Buetefisch

Emory University

Phone: 404-712-5507

Email: cathrin.buetefisch@emory.edu

Results disclosure agreements

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