Modulating Interaction of Motor Learning Networks in Rehabilitation of Stroke
Sponsor
University of Michigan (Other)
Overall Status
Completed
CT.gov ID
NCT03086551
Collaborator
(none)
12
1
2
35.9
0.3
Study Details
Study Description
Brief Summary
This study uses a form on non-invasive brain stimulation called transcranial magnetic stimulation to understand 1) understand how the brain learns post-stroke and 2) assess non-invasive brain stimulation as an addition to current stroke rehabilitation approaches. In two study arms the investigators will compare the effect of active transcranial magnetic stimulation paired with motor practice with placebo (or sham) transcranial magnetic stimulation paired with the same motor practice.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Stroke is the leading cause of permanent disability in the United States. In the absence of treatments to restore the lost tissue, clinical scientists have focused upon repetitive forced used of the paretic limb to promote neural reorganization in preserved tissue and reduce disability. However, forced use interventions are time intensive and the extent of functional recovery is variable. One potential contributor to this variability is the potential trade-off between compensatory cognitive motor control strategies and the extent of procedural learning that can occur. Compensatory strategies adopted by patients may produce quick short-term increases in performance but retard slower sustained improvements by interfering with development of procedural learning. Consistent with this hypothesis, the investigators' previous work documents an increased reliance upon dorsolateral prefrontal cortex during performance of learned skills post-stoke. However, the investigators' previous work also demonstrates that the effect of increased activity in dorsolateral prefrontal cortex may limit reorganization in important areas involved in the consolidation of practice thereby limiting functional recovery post-stroke.
Transcranial magnetic stimulation offers a unique opportunity to investigate the relationship between dorsolateral prefrontal cortex activity and consolidation of motor practice/rehabilitaion post-stroke. Here the investigators' objective is to determine whether suppression of the contralesional dorsolateral prefrontal cortex, with continuous theta burst transcranial magnetic brain stimulation (cTBS), a form of transcranial magnetic stimulation, prior to motor practice enhances brain reorganization in critical areas and leads to greater sustained improvements in motor ability over time.
The proposed work will enhance the understanding of motor learning post-stroke and provide preliminary evidence for the benefits of dorsolateral prefrontal cTBS as an adjunct to current rehabilitation interventions.
Study Design
Study Type:
Interventional
Actual Enrollment
:
12 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Basic Science
Official Title:
Modulating Interaction of Motor Learning Networks in Rehabilitation of Stroke
Actual Study Start Date
:
Apr 1, 2016
Actual Primary Completion Date
:
Mar 30, 2019
Actual Study Completion Date
:
Mar 30, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental Application of active continuous theta burst stimulation over dorsolateral prefrontal cortex prior to upper limb motor practice. |
Device: Active continuous theta burst stimulation (cTBS)
Active cTBS over dorsolateral prefrontal cortex that has an effect upon dorsolateral prefrontal cortex brain activity.
Behavioral: Motor Practice
Upper limb reaching task to be practiced. Practice will be paired with Active/Sham stimulation. Twenty trials will occur before Active/Sham stimulation. 40 trials will be practiced after Active/Sham stimulation.
|
| Placebo Comparator: Control Application of sham continuous theta burst stimulation over dorsolateral prefrontal cortex prior to upper limb motor practice. |
Device: Placebo (Sham) continuous theta burst stimulation
Sham stimulation over dorsolateral prefrontal cortex that looks and sounds like active cTBS but does not have any effect upon dorsolateral prefrontal cortex brain activity.
Behavioral: Motor Practice
Upper limb reaching task to be practiced. Practice will be paired with Active/Sham stimulation. Twenty trials will occur before Active/Sham stimulation. 40 trials will be practiced after Active/Sham stimulation.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Sequential Response Time to Post-Intervention [Baseline and post-intervention]
Aggregate time to complete movements between a six sequential targets presented on a computer touch screen in front of the participant. The mean of ten sequences was calculated prior to any practice and at a delayed retention test (e.g. no warm up or preceding practice) post-intervention. Change between the baseline average and post-intervention average was also calculated by subtracting post-intervention score from pre-intervention score. Positive numbers represent improvement in ability.
Secondary Outcome Measures
- Change From Baseline in Time to Complete the Jebsen-Taylor Hand Function Test [Baseline and post-intervention]
The Jebsen-Taylor Hand Function Test is comprised of a series of unimanual tasks required for activities of daily living. Time to complete the Jebsen-Taylor Hand Function Test was assessed at baseline and post-intervention by taking the aggregate time to complete each activity. Change in time to complete the Jebsen-Taylor Hand Function Test between the baseline and post-intervention tests was derived by subtracting post-intervention score from baseline score. Positive scores indicate improvement in functional motor ability.
- Change in Sequential Response Time Immediately Follow an Individual Bout of Non-invasive Brain Stimulation (e.g. Within Session) [Within session baseline to ~8 minutes post-application of non-invasive stimulation within the same session]
Aggregate time to complete movements between a six sequential targets presented on a computer touch screen in front of the participant. The mean of ten sequences was calculated prior to application of Active+Motor Practice or Sham+Motor Practice for each intervention session and the first ten sequences of practice immediately following the specific form of non-invasive brain stimulation within each session. Change within a session was calculated by subtracting the post-stimulation score from the pre-stimulation score within a session. Positive values represent improved ability.
- Motor Evoked Potential Amplitude (in Microvolts) at Pre-baseline and Post-Intervention [Baseline and post-intervention]
Motor evoked potential amplitude evoked by transcranial magnetic brain stimulation was recorded using electromyography over the first dorsal interosseous muscle of the stroke-affected hand. The means of ten trials at 120% (linear part of recruitment curve) and ten trials at 150% (recruitment curve plateau) of resting motor threshold were calculated and expressed in microvolts.
- Change From Baseline in Cortical Excitability Post-Intervention [Baseline and post-intervention]
Motor evoked potential amplitude evoked by transcranial magnetic brain stimulation was recorded using electromyography over the first dorsal interosseous muscle of the stroke-affected hand. The means of ten trials at 120% (linear part of recruitment curve) and ten trials at 150% (recruitment curve plateau) of resting motor threshold were calculated and expressed in microvolts. Change in motor evoked potential amplitude elicited by transcranial magnetic stimulation intensities of 120% (linear part of recruitment curve) and ten trials at 150% (recruitment curve plateau) of resting motor threshold. Values are expressed percent change relative to pre-baseline values. Positive numbers represent an increase motor evoked potential from pre-baseline to post-intervention.
Eligibility Criteria
Criteria
Ages Eligible for Study:
50 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age between 50-75 years
-
movement-related deficit associated with first time middle cerebral artery stroke
-
greater than 6-months post-stroke
-
Fugl-Meyer score between 15 and 60
-
ability to elicit a motor evoked potential from the ipsilesional cortex
Exclusion Criteria:
-
a score <27 on the Mini-Mental Status Exam
-
a score of <123 on the Mattis Dementia Rating Scale
-
a score of <13 on the Frenchay Aphasia Screen
-
a history of seizure/epilepsy, head trauma, major psychiatric diagnosis, neurodegenerative disorder or substance abuse
-
a history of congestive heart failure
-
systolic blood pressure above 120 mmHg and/or diastolic pressure above 80 mmHg
-
the taking of any GABAergic, NMDA-receptor antagonist or other drug known to influence the neural receptors that facilitate neural plasticity
-
an infarct resulting from ischemic stroke of anterior or posterior cerebral artery OR an infarct that encroaches within 2cm of the site of cTBS stimulation
-
absence of an MEP in response to single pulse transcranial magnetic stimulation over ipsilesional M1 and 10) any other contraindication to TMS or MRI.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Human Sensorimotor Laboratory, School of Kinesiology, University of Michigan | Ann Arbor | Michigan | United States | 48103 |
Sponsors and Collaborators
- University of Michigan
Investigators
- Principal Investigator: Sean K Meehan, PhD, Sch. of Kinesiology, Univ. of Michigan
Study Documents (Full-Text)
More Information
Additional Information:
Publications
- Brodie SM, Meehan S, Borich MR, Boyd LA. 5 Hz repetitive transcranial magnetic stimulation over the ipsilesional sensory cortex enhances motor learning after stroke. Front Hum Neurosci. 2014 Mar 21;8:143. doi: 10.3389/fnhum.2014.00143. eCollection 2014.
- Meehan SK, Dao E, Linsdell MA, Boyd LA. Continuous theta burst stimulation over the contralesional sensory and motor cortex enhances motor learning post-stroke. Neurosci Lett. 2011 Aug 1;500(1):26-30. doi: 10.1016/j.neulet.2011.05.237. Epub 2011 Jun 12.
- Meehan SK, Randhawa B, Wessel B, Boyd LA. Implicit sequence-specific motor learning after subcortical stroke is associated with increased prefrontal brain activations: an fMRI study. Hum Brain Mapp. 2011 Feb;32(2):290-303. doi: 10.1002/hbm.21019.
Responsible Party:
Sean Meehan,
Assistant Professor,
University of Waterloo
ClinicalTrials.gov Identifier:
NCT03086551
Other Study ID Numbers:
- 1R03NS096484-01
First Posted:
Mar 22, 2017
Last Update Posted:
Apr 27, 2020
Last Verified:
Apr 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
Yes
Keywords provided by Sean Meehan,
Assistant Professor,
University of Waterloo
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Recruitment was conducted through mailings to individuals identified as having been admitted to the University of Michigan Health System in the past 5 years (from 01/01/2012 to 01/27/2017) for treatment of middle cerebral artery stroke. Mailings were sent to those individuals with zip codes in the state of Michigan and northwest Ohio. |
|---|---|
| Pre-assignment Detail | Enrolled participants were excluded prior to randomization for: known contraindication to the transcranial magnetic stimulation intervention (n=1) and a broken foot, not study related, between enrollment and randomization (n=1). |
| Arm/Group Title | Active+Motor Practice, Then Sham+Motor Practice | Sham+Motor Practice, Then Active+Motor Practice |
|---|---|---|
| Arm/Group Description | Participants first completed four sessions in which motor practice was preceded by ACTIVE continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex. After a three-week washout period participants then completed four sessions in which motor practice was preceded by SHAM continuous theta burst stimulation over dorsolateral prefrontal cortex. | Participants first completed four sessions in which motor practice was preceded by SHAM continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex. After a three-week washout period participants then completed four sessions in which motor practice was preceded by ACTIVE continuous theta burst stimulation over dorsolateral prefrontal cortex. |
| Period Title: First Intervention | ||
| STARTED | 5 | 5 |
| COMPLETED | 4 | 4 |
| NOT COMPLETED | 1 | 1 |
| Period Title: First Intervention | ||
| STARTED | 4 | 4 |
| COMPLETED | 1 | 1 |
| NOT COMPLETED | 3 | 3 |
| Period Title: First Intervention | ||
| STARTED | 1 | 1 |
| COMPLETED | 1 | 1 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Active+Motor Practice, Then Sham+Motor Practice | Sham+Motor Practice, Then Active+Motor Practice | Total |
|---|---|---|---|
| Arm/Group Description | Participants first completed four sessions in which motor practice was preceded by ACTIVE continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex. After a three-week washout period participants then completed four sessions in which motor practice was preceded by SHAM continuous theta burst stimulation over dorsolateral prefrontal cortex. | Participants first completed four sessions in which motor practice was preceded by SHAM continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex. After a three-week washout period participants then completed four sessions in which motor practice was preceded by ACTIVE continuous theta burst stimulation over dorsolateral prefrontal cortex. | Total of all reporting groups |
| Overall Participants | 5 | 5 | 10 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
3
60%
|
4
80%
|
7
70%
|
| >=65 years |
2
40%
|
1
20%
|
3
30%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
58
(10)
|
59
(10)
|
58
(9)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
3
60%
|
3
60%
|
6
60%
|
| Male |
2
40%
|
2
40%
|
4
40%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
2
40%
|
2
20%
|
| Not Hispanic or Latino |
5
100%
|
3
60%
|
8
80%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
5
100%
|
3
60%
|
8
80%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
2
40%
|
2
20%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
5
100%
|
5
100%
|
10
100%
|
| Fugl-Meyer Assessment of Motor Recovery After Stroke (Upper Limb) (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
50
(17)
|
48
(24)
|
49
(20)
|
| Montreal Cognitive Assessment (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
28
(2)
|
24
(3)
|
26
(3)
|
| Mini-Mental State Examination (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
30
(1)
|
27
(3)
|
29
(2)
|
| Trail Making Test A (seconds) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [seconds] |
29.6
(6.9)
|
31.1
(13.3)
|
30.3
(9.5)
|
| Trail Making Test B (seconds) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [seconds] |
29.6
(33.1)
|
89.7
(26.2)
|
75.3
(31.1)
|
| Stroke Affected Hemisphere (Count of Participants) | |||
| Left Hemisphere |
2
40%
|
4
80%
|
6
60%
|
| Right Hemisphere |
3
60%
|
1
20%
|
4
40%
|
Outcome Measures
| Title | Change From Baseline in Sequential Response Time to Post-Intervention |
|---|---|
| Description | Aggregate time to complete movements between a six sequential targets presented on a computer touch screen in front of the participant. The mean of ten sequences was calculated prior to any practice and at a delayed retention test (e.g. no warm up or preceding practice) post-intervention. Change between the baseline average and post-intervention average was also calculated by subtracting post-intervention score from pre-intervention score. Positive numbers represent improvement in ability. |
| Time Frame | Baseline and post-intervention |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who completed at least one arm of the study |
| Arm/Group Title | Active+Motor Practice | Sham+Motor Practice |
|---|---|---|
| Arm/Group Description | Participants who received motor practice preceded by ACTIVE continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex in either the first three weeks or last three weeks of the study. | Participants who received motor practice preceded by SHAM continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex in either the first three weeks or last three weeks of the study. |
| Measure Participants | 5 | 5 |
| Time to Complete Sequence (Baseline) |
8.68
(2.06)
|
8.84
(1.47)
|
| Time to Complete Sequence (Delayed Retention) |
8.32
(1.55)
|
7.96
(1.04)
|
| Change in Time (Pre to Post) |
0.37
(0.65)
|
0.88
(0.63)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | Magnitude of change in sequence completion time from pre-baseline to post-intervention for the Active arm. Cohen's d was calculated as a measure of effect size. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | 0.20 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as time to complete the sequence at the pre-baseline assessment minus the time it took to complete the sequence at the post-intervention assessment. The denominator reflected pooled variance. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | Magnitude of change in sequence completion time from pre-baseline to post-intervention for the Sham arm. Cohen's d was calculated as a measure of effect size. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | 0.69 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as time to complete the sequence at the pre-baseline assessment minus the time it took to complete the sequence at the post-intervention assessment. The denominator reflected pooled variance. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Cohen's d effect size was calculated to compare the magnitude of change in time to complete the movement sequence from pre-baseline to post-intervention across the Active and Sham arms. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | -0.80 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the change from pre- to post-intervention for the Active arm minus change from pre- to post-intervention for the Sham arm. The denominator reflected pooled variance. | |
| Title | Change From Baseline in Time to Complete the Jebsen-Taylor Hand Function Test |
|---|---|
| Description | The Jebsen-Taylor Hand Function Test is comprised of a series of unimanual tasks required for activities of daily living. Time to complete the Jebsen-Taylor Hand Function Test was assessed at baseline and post-intervention by taking the aggregate time to complete each activity. Change in time to complete the Jebsen-Taylor Hand Function Test between the baseline and post-intervention tests was derived by subtracting post-intervention score from baseline score. Positive scores indicate improvement in functional motor ability. |
| Time Frame | Baseline and post-intervention |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who completed at least one arm of the study |
| Arm/Group Title | Active+Motor Practice | Sham+Motor Practice |
|---|---|---|
| Arm/Group Description | Participants who received motor practice preceded by ACTIVE continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex in either the first three weeks or last three weeks of the study. | Participants who received motor practice preceded by SHAM continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex in either the first three weeks or last three weeks of the study. |
| Measure Participants | 5 | 5 |
| Pre Time to Complete (Stroke Affected Limb) |
95.68
(51.71)
|
86.07
(17.78)
|
| Post Time to Complete (Stroke Affected Limb) |
100.05
(60.47)
|
76.27
(20.97)
|
| Change Pre to Post (Stroke Affected Limb) |
-4.38
(8.95)
|
9.80
(6.14)
|
| Pre Time to Complete (Non-Stroke Affected Limb) |
55.75
(11.22)
|
66.67
(20.87)
|
| Post Time to Complete (Non-Stroke Affected Limb) |
51.97
(8.25)
|
64.95
(24.07)
|
| Change Pre to Post (Non-Stroke Affected Limb) |
3.78
(5.33)
|
1.72
(5.40)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | The magnitude of transfer of the task specific practice to functional activities of daily live for the stroke affected limb was assessed by calculating the magnitude of change (Cohen's d) in time to complete the activities of the Jebsen-Taylor Hand Function Test from pre-baseline to post-intervention in the Active arm. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | -0.08 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as aggregate time to complete all elements at the pre-baseline assessment minus the aggregate time it took to complete all elements at the post-intervention assessment. The denominator reflected pooled variance. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | The magnitude of transfer of the task specific practice to functional activities of daily live for the stroke affected limb was assessed by calculating the magnitude of change (Cohen's d) in time to complete the activities of the Jebsen-Taylor Hand Function Test from pre-baseline to post-intervention in the Sham arm. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | 0.50 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as aggregate time to complete all elements at the pre-baseline assessment minus the aggregate time it took to complete all elements at the post-intervention assessment. The denominator reflected pooled variance. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | Comparison across study arm of the magnitude of improvement in aggregate time to complete all elements of the Jebsen-Taylor Hand Function Test for the stroke affected limb. Cohen's d was calculated as a measure of effect size. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | -1.84 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the change from pre- to post-intervention for the Active arm minus the change from pre- to post-intervention for the Sham arm. The denominator reflected pooled variance. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | The magnitude of transfer of the task specific practice to functional activities of daily live for the non-stroke affected limb was assessed by calculating the magnitude of change (Cohen's d) in time to complete the activities of the Jebsen-Taylor Hand Function Test from pre-baseline to post-intervention in the Active arm. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | 0.38 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as aggregate time to complete all elements at the pre-baseline assessment minus the aggregate time it took to complete all elements at the post-intervention assessment. The denominator reflected pooled variance. | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | The magnitude of transfer of the task specific practice to functional activities of daily live for the non-stroke affected limb was assessed by calculating the magnitude of change (Cohen's d) in time to complete the activities of the Jebsen-Taylor Hand Function Test from pre-baseline to post-intervention in the Sham arm. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | 0.08 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as aggregate time to complete all elements at the pre-baseline assessment minus the aggregate time it took to complete all elements at the post-intervention assessment. The denominator reflected pooled variance. | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | Comparison across study arm of the magnitude of improvement in aggregate time to complete all elements of the Jebsen-Taylor Hand Function Test for the non-stroke affected limb. Cohen's d was calculated as a measure of effect size. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | 0.38 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the change from pre- to post-intervention for the Active arm minus the change from pre- to post-intervention for the Sham arm. The denominator reflected pooled variance. | |
| Title | Change in Sequential Response Time Immediately Follow an Individual Bout of Non-invasive Brain Stimulation (e.g. Within Session) |
|---|---|
| Description | Aggregate time to complete movements between a six sequential targets presented on a computer touch screen in front of the participant. The mean of ten sequences was calculated prior to application of Active+Motor Practice or Sham+Motor Practice for each intervention session and the first ten sequences of practice immediately following the specific form of non-invasive brain stimulation within each session. Change within a session was calculated by subtracting the post-stimulation score from the pre-stimulation score within a session. Positive values represent improved ability. |
| Time Frame | Within session baseline to ~8 minutes post-application of non-invasive stimulation within the same session |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who completed at least one arm of the study |
| Arm/Group Title | Active+Motor Practice | Sham+Motor Practice |
|---|---|---|
| Arm/Group Description | Participants who received motor practice preceded by ACTIVE continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex in either the first three weeks or last three weeks of the study. | Participants who received motor practice preceded by SHAM continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex in either the first three weeks or last three weeks of the study. |
| Measure Participants | 5 | 5 |
| Session 1 |
0.41
(0.70)
|
0.89
(0.36)
|
| Session 2 |
0.72
(1.97)
|
0.80
(1.86)
|
| Session 3 |
-0.20
(0.60)
|
0.22
(0.62)
|
| Session 4 |
0.35
(0.46)
|
0.23
(0.39)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | The immediate effect of continuous theta burst stimulation over dorsolateral prefrontal cortex prior to practice was assessed by determining the magnitude of the effect of Active stimulation from pre-intervention to immediately post-intervention in Session 1 of the intervention. Cohen's d was used to derive effect size. The Sham stimulation change was used as the control. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | -0.86 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the change from pre- to immediately post-stimulation (within the same session) for the Active arm minus the change from pre- to immediately post-stimulation for the Sham arm. The denominator reflected pooled variance. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | The immediate effect of continuous theta burst stimulation over dorsolateral prefrontal cortex prior to practice was assessed by determining the magnitude of the effect of Active stimulation from pre-intervention to immediately post-intervention in Session 2 of the intervention. Cohen's d was used to derive effect size. The Sham stimulation change was used as the control. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the change from pre- to immediately post-stimulation (within the same session) for the Active arm minus the change from pre- to immediately post-stimulation for the Sham arm. The denominator reflected pooled variance. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | The immediate effect of continuous theta burst stimulation over dorsolateral prefrontal cortex prior to practice was assessed by determining the magnitude of the effect of Active stimulation from pre-intervention to immediately post-intervention in Session 3 of the intervention. Cohen's d was used to derive effect size. The Sham stimulation change was used as the control. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | -0.69 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the change from pre- to immediately post-stimulation (within the same session) for the Active arm minus the change from pre- to immediately post-stimulation for the Sham arm. The denominator reflected pooled variance. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | The immediate effect of continuous theta burst stimulation over dorsolateral prefrontal cortex prior to practice was assessed by determining the magnitude of the effect of Active stimulation from pre-intervention to immediately post-intervention in Session 4 of the intervention. Cohen's d was used to derive effect size. The Sham stimulation change was used as the control. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | 0.28 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the change from pre- to immediately post-stimulation (within the same session) for the Active arm minus the change from pre- to immediately post-stimulation for the Sham arm. The denominator reflected pooled variance. | |
| Title | Motor Evoked Potential Amplitude (in Microvolts) at Pre-baseline and Post-Intervention |
|---|---|
| Description | Motor evoked potential amplitude evoked by transcranial magnetic brain stimulation was recorded using electromyography over the first dorsal interosseous muscle of the stroke-affected hand. The means of ten trials at 120% (linear part of recruitment curve) and ten trials at 150% (recruitment curve plateau) of resting motor threshold were calculated and expressed in microvolts. |
| Time Frame | Baseline and post-intervention |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who completed at least one arm of the study |
| Arm/Group Title | Active+Motor Practice | Sham+Motor Practice |
|---|---|---|
| Arm/Group Description | Participants who received motor practice preceded by ACTIVE continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex in either the first three weeks or last three weeks of the study. | Participants who received motor practice preceded by SHAM continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex in either the first three weeks or last three weeks of the study. |
| Measure Participants | 5 | 5 |
| MEP Amplitude Pre (120% of RMT) |
1558
(1020)
|
971
(709)
|
| MEP Amplitude Post (120% of RMT) |
1216
(1161)
|
511
(279)
|
| MEP Amplitude Pre (150% of RMT) |
2750
(2172)
|
1977
(218)
|
| MEP Amplitude Post (150% of RMT) |
2008
(2062)
|
2495
(609)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | Comparison of first dorsal interosseous motor evoked potential (MEP) amplitude elicited from the ipsilesional motor cortex pre-baseline to post-intervention for the Active arm when transcranial magnetic stimulator intensity was set to 120% of resting motor threshold. Estimate of effect size was derived using Cohen's d. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | -0.31 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the amplitude of the motor evoked potential at the post-intervention assessment minus the amplitude of the motor evoked potential at the pre-baseline assessment. The denominator reflected pooled variance. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | Comparison of first dorsal interosseous motor evoked potential (MEP) amplitude elicited from the ipsilesional motor cortex pre-baseline to post-intervention for the Sham arm when transcranial magnetic stimulator intensity was set to 120% of resting motor threshold. Estimate of effect size was derived using Cohen's d. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | -0.85 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the amplitude of the motor evoked potential at the post-intervention assessment minus the amplitude of the motor evoked potential at the pre-baseline assessment. The denominator reflected pooled variance. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | Comparison of the first dorsal interosseous motor evoked potential (MEP) amplitude elicited from the ipsilesional motor cortex pre-baseline to post-intervention for the Active arm when transcranial magnetic stimulator intensity was set to 150% of resting motor threshold. Estimate of effect size was derived using Cohen's d. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | -0.35 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the amplitude of the motor evoked potential at the post-intervention assessment minus the amplitude of the motor evoked potential at the pre-baseline assessment. The denominator reflected pooled variance. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | Comparison of the first dorsal interosseous motor evoked potential (MEP) amplitude elicited from the ipsilesional motor cortex pre-baseline to post-intervention for the Sham arm when transcranial magnetic stimulator intensity was set to 150% of resting motor threshold. Estimate of effect size was derived using Cohen's d. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | 1.13 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the amplitude of the motor evoked potential at the post-intervention assessment minus the amplitude of the motor evoked potential at the pre-baseline assessment. The denominator reflected pooled variance. | |
| Title | Change From Baseline in Cortical Excitability Post-Intervention |
|---|---|
| Description | Motor evoked potential amplitude evoked by transcranial magnetic brain stimulation was recorded using electromyography over the first dorsal interosseous muscle of the stroke-affected hand. The means of ten trials at 120% (linear part of recruitment curve) and ten trials at 150% (recruitment curve plateau) of resting motor threshold were calculated and expressed in microvolts. Change in motor evoked potential amplitude elicited by transcranial magnetic stimulation intensities of 120% (linear part of recruitment curve) and ten trials at 150% (recruitment curve plateau) of resting motor threshold. Values are expressed percent change relative to pre-baseline values. Positive numbers represent an increase motor evoked potential from pre-baseline to post-intervention. |
| Time Frame | Baseline and post-intervention |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who completed at least one arm of the study |
| Arm/Group Title | Active+Motor Practice | Sham+Motor Practice |
|---|---|---|
| Arm/Group Description | Participants who received motor practice preceded by ACTIVE continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex in either the first three weeks or last three weeks of the study. | Participants who received motor practice preceded by SHAM continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex in either the first three weeks or last three weeks of the study. |
| Measure Participants | 5 | 5 |
| % change in MEP (120% RMT) |
-26
(35)
|
-19
(58)
|
| % change in MEP (150% RMT) |
-17
(37)
|
25
(17)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | Comparison of the first dorsal interosseous motor evoked potential (MEP) amplitude elicited from the ipsilesional motor cortex pre-baseline to post-intervention across the Active and Sham arms when transcranial magnetic stimulator intensity was set to 120% of resting motor threshold. Comparison quantified as effect size using Cohen's d. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | -0.15 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the change from pre- to post-intervention for the Active arm minus the change from pre- to post-intervention for the Sham arm. The denominator reflected pooled variance. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Active+Motor Practice, Sham+Motor Practice |
|---|---|---|
| Comments | Comparison of the first dorsal interosseous motor evoked potential (MEP) amplitude elicited from the ipsilesional motor cortex pre-baseline to post-intervention across the Active and Sham arms when transcranial magnetic stimulator intensity was set to 150% of resting motor threshold. Comparison quantified as effect size using Cohen's d. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Effect Size - Cohen's d |
| Estimated Value | -1.46 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Cohen's d was calculated as the change from pre- to post-intervention for the Active arm minus the change from pre- to post-intervention for the Sham arm. The denominator reflected pooled variance. | |
Adverse Events
| Time Frame | Duration of study (9 weeks) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The total numbers reported reflect all participants who completed at least one session of the intervention. | |||
| Arm/Group Title | Active+Motor Practice | Sham+Motor Practice | ||
| Arm/Group Description | Participants who received motor practice preceded by ACTIVE continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex in either the first three weeks or last three weeks of the study. | Participants who received motor practice preceded by SHAM continuous theta burst stimulation (cTBS) over dorsolateral prefrontal cortex in either the first three weeks or last three weeks of the study. | ||
All Cause Mortality |
||||
| Active+Motor Practice | Sham+Motor Practice | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/5 (0%) | 0/5 (0%) | ||
Serious Adverse Events |
||||
| Active+Motor Practice | Sham+Motor Practice | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/5 (0%) | 0/5 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Active+Motor Practice | Sham+Motor Practice | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/5 (0%) | 0/5 (0%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Sean K Meehan, PhD |
|---|---|
| Organization | University of Waterloo, Waterloo, Ontario, Canada |
| Phone | 5198884567 ext 39278 |
| skmeehan@uwaterloo.ca |
Responsible Party:
Sean Meehan,
Assistant Professor,
University of Waterloo
ClinicalTrials.gov Identifier:
NCT03086551
Other Study ID Numbers:
- 1R03NS096484-01
First Posted:
Mar 22, 2017
Last Update Posted:
Apr 27, 2020
Last Verified:
Apr 1, 2020