Repetitive Transcranial Magnetic Stimulation Use in Acute Stroke

• Sponsor: University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT01922986
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arms: 2
• Duration (Months): 17.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

When a certain area of the brain is injured, like in stroke, several events occur. One side of the body may become weak. This weakness is called hemiparesis and it may create difficulty in performing tasks like writing, eating, and walking. The weakness results from two sources:

1. death of some brain cells in the affected side (hemisphere) of the brain

2. exaggerated inhibitory signals from the unaffected hemisphere acting on surviving neurons in the affected hemisphere.

Investigators cannot change neurons that have died but they may be able to change the exaggerated inhibition that impairs the surviving neurons in the affected hemisphere.The purpose of this study is to try to decrease the exaggerated inhibition coming from the unaffected hemisphere, which suppresses the affected hemisphere, with transcranial magnetic stimulation (TMS). Investigators hypothesize that, from admission to discharge, active rTMS combined with conventional therapy will produce greater functional gains in the paretic hand compared to sham rTMS combined with conventional therapy, as measured by standard tests.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Device: active rTMS; Device: sham rTMS; Behavioral: conventional stroke therapy	N/A

Detailed Description

Stroke is the leading cause of long-term disability in the United States and people with stroke deserve our maximum effort to restore in them as much function as possible; yet, mainstream stroke rehabilitation remains mired in traditional treatment approaches that may be suboptimal. However, for the past 5 years we have been endeavoring to advance stroke rehabilitation by including noninvasive brain stimulation. This study will explore whether the safety and functional results from noninvasive brain stimulation in patients with chronic stroke when given by researchers in a laboratory setting can be replicated in acute stroke when given by trained clinicians in the real-world clinical setting.

As background, a phenomenon in stroke is that compensatory overuse of the non-stroke hemisphere can inhibit surviving neurons in the stroke hemisphere. In this way, people with stroke are "doubly disabled" - first, by the stroke itself and, second, by exaggerated interhemispheric inhibition (IHI) arising in the non-stroke hemisphere and acting on surviving neurons in the non-stroke hemisphere. Investigators cannot bring the killed neurons back to life but they can up-regulate the surviving neurons suppressed by IHI. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive way to do this.

rTMS has not yet entered mainstream clinical use for stroke, likely because it has not been explored in the acute rehabilitation setting with application by clinicians. With prior National Institutes of Health funding, Dr. Carey has considerable experience in using rTMS in the laboratory setting for chronic stroke. He will now take rTMS out of his lab and into the real-world setting of Courage Kenny Rehabilitation Institute (CKRI), the primary referral center for acute stroke rehabilitation in our region, where clinicians will be trained in rTMS. Five daily rTMS treatments (active or sham) will be given to the non-stroke primary motor area (M1). After each treatment, patients will receive their conventional rehabilitation training. This approach is innovative because of the rTMS parameters used and because the application will be given by trained clinicians with oversight by the Principal Investigator, as opposed to laboratory researchers. Expected outcomes are improved hand function with no major adverse effects. Data will serve as a springboard to larger clinical trials.

Specific Aim #1: Determine the safety of 5 treatments of 6-Hz primed low-frequency rTMS combined with conventional therapy in adults with acute stroke.

Adverse effects will be measured through observation for seizures, investigator screening, physician exam, and tests of cognitive function and motor function in the nonparetic hand.

Investigators hypothesize there will be a) no seizures, b) no cognitive decline and c) no motor decline.

Specific Aim #2: Compare the effectiveness of active vs. sham rTMS on functional outcomes in adults with acute stroke.

Adults with acute stroke will be randomized to receive either active rTMS or sham rTMS. Both groups will also receive conventional therapy, consisting of the normal rehabilitation used at this rehabilitation center. Investigators hypothesize that, from admission to discharge, active rTMS will produce greater functional gains in the paretic hand compared to sham rTMS, as measured by standard tests.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Real vs Sham rTMS Combined With Conventional Therapy in Acute Stroke
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active rTMS with conventional therapy 20 minutes of active rTMS followed by conventional stroke therapy	Device: active rTMS; 10 minutes of real high-frequency (6-Hz) rTMS priming (total priming pulses = 600) plus 10 minutes of low-rate (1Hz) rTMS (total low-rate pulses = 600).; Behavioral: conventional stroke therapy; conventional stroke therapy consisting of exercises and physical training
Sham Comparator: sham rTMS with conventional therapy 20 minutes of sham rTMS stimulation followed by conventional stroke therapy	Device: sham rTMS; 20 minutes of sham rTMS stimulation; Behavioral: conventional stroke therapy; conventional stroke therapy consisting of exercises and physical training

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Jebsen Taylor Hand Function Test Scores [Measured at pretest (day before treatments begin) and posttest (day following last treatment). Thus, 7 days of participation (1 pretest, 5 treatments, 1 posttest).]

   This test quantifies the time it takes for the subject to do the following standardized functional tasks with the hand: stack three checkers, turn over cards, turn over empty cans, turn over fluid-filled cans, pick up and place small items like a paper clip, etc into a can, and use a spoon to scoop up a bean and drop the bean into a can. The unit of measure is time and changes that are negative signify reduced time at posttest compared to pretest, which would be an improvement. Total score = sum of times for each subtests

Secondary Outcome Measures

1. Change in Finger Tracking Test [Measured at pretest (day before treatments begin) and posttest (day following last treatment). Thus, 7 days of participation (1 pretest, 5 treatments, 1 posttest).]

   This test involves placing a device on the hand that shows the changing angle of the finger joint on a computer screen as the joint is moved. The computer screen also shows a target line, such as a sine wave. At the start of the test, the computer screen cursor moves horizontally across the target and the subject moves the finger joint into extension or flexion to adjust the vertical position of the cursor to that it traces the target line as accurately as possible. The performance is quantified by calculating the root-mean-square error between the target line and the response line. This is converted into an Accuracy Index, which has a maximum value of 100% (perfect score). Negative values can occur and reach a value of -100%, signifying very poor performance. Typical scores for healthy range from 50-80%. Typical values in stroke range from -100 to +40%. Changes that are positive signify increased tracking accuracy at posttest compared to pretest, which would be an improvement.

2. Change in Motricity Index [Measured at pretest (day before treatments begin) and posttest (day following last treatment). Thus, 7 days of participation (1 pretest, 5 treatments, 1 posttest).]

   Measures strength in finger pinch, elbow flexion and arm abduction. 0 No pinch movement. 11 Slight movement of finger or thumb. 19 Able to grip the cube, but not hold it against gravity. 22 Able to grip and hold the cube against gravity, but not against a weak pull by examiner. The weighted score based on the ordinal 6 point scale 26 Able to grip and hold the cube against a weak pull, but weaker than the other side. 33 Normal pinch grip. For shoulder and elbow scoring is: 0 No movement. 9 Palpable contraction in muscle, but no movement. 14 Visible movement, but not full range and not against gravity. 19 Full range of movement against gravity but not against resistance. 25 Full movement against resistance, but weaker than the other side. 33 Normal power. Maximum total score is 99, minimum is 0. Changes that are positive signify improved strength at postte

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• stroke onset: within past 30 days but rTMS intervention will commence no sooner than 5 days from stroke onset

• stroke location: cortical or subcortical

• stroke type: ischemic

• age: >18 years

• paretic index finger must show either no or impaired flexion/extension motion at the metacarpophalangeal (MP) joint.

• Mini-Mental State Examination greater than or equal to 22

• ability to stand/transfer with no more than moderate assistance

Exclusion Criteria:

• seizure within past two years

• metal in head (dental permitted)

• pregnancy

• psychiatric disorders

• receiving tricyclic antidepressants or neuroleptics

• inability to follow three-step command

• hemineglect

• dependent on ventilator, nasogastric tube, or implanted medical device

• co-morbidities impairing upper extremity function

• anticipated stay at Courage Kenny Rehabilitation Institute shorter than 7 treatment days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Courage Kenny Rehabilitation Institute	Minneapolis	Minnesota	United States	55407

Sponsors and Collaborators

• University of Minnesota

Investigators

• Principal Investigator: James R Carey, PhD, PT, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT01922986
• Other Study ID Numbers: Acute_rTMS
• First Posted: Aug 14, 2013
• Last Update Posted: May 25, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of Minnesota: stroke; rehabilitation; hemiplegia; repetitive transcranial magnetic stimulation
• Additional relevant MeSH terms: Stroke

Study Results

Participant Flow

Arm/Group Title	Active rTMS With Conventional Therapy	Sham rTMS With Conventional Therapy
Arm/Group Description	20 minutes of active rTMS followed by conventional stroke therapy active rTMS: 10 minutes of real high-frequency (6-Hz) rTMS priming (total priming pulses = 600) plus 10 minutes of low-rate (1Hz) rTMS (total low-rate pulses = 600). conventional stroke therapy: conventional stroke therapy consisting of exercises and physical training	20 minutes of sham rTMS stimulation followed by conventional stroke therapy sham rTMS: 20 minutes of sham rTMS stimulation conventional stroke therapy: conventional stroke therapy consisting of exercises and physical training
Period Title: Overall Study
STARTED	2	2
COMPLETED	2	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Active rTMS With Conventional Therapy	Sham rTMS With Conventional Therapy	Total
Arm/Group Description	20 minutes of active rTMS followed by conventional stroke therapy active rTMS: 10 minutes of real high-frequency (6-Hz) rTMS priming (total priming pulses = 600) plus 10 minutes of low-rate (1Hz) rTMS (total low-rate pulses = 600). conventional stroke therapy: conventional stroke therapy consisting of exercises and physical training	20 minutes of sham rTMS stimulation followed by conventional stroke therapy sham rTMS: 20 minutes of sham rTMS stimulation conventional stroke therapy: conventional stroke therapy consisting of exercises and physical training	Total of all reporting groups
Overall Participants	2	2	4
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 50%	1 50%	2 50%
>=65 years	1 50%	1 50%	2 50%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.5 (19.1)	52.5 (23.3)	63.0 (21.2)
Sex: Female, Male (Count of Participants)
Female	1 50%	0 0%	1 25%
Male	1 50%	2 100%	3 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	2 100%	2 100%	4 100%
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	2 100%	2 100%	4 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	2 100%	4 100%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Jebsen Taylor Hand Function Test Scores
Description	This test quantifies the time it takes for the subject to do the following standardized functional tasks with the hand: stack three checkers, turn over cards, turn over empty cans, turn over fluid-filled cans, pick up and place small items like a paper clip, etc into a can, and use a spoon to scoop up a bean and drop the bean into a can. The unit of measure is time and changes that are negative signify reduced time at posttest compared to pretest, which would be an improvement. Total score = sum of times for each subtests
Time Frame	Measured at pretest (day before treatments begin) and posttest (day following last treatment). Thus, 7 days of participation (1 pretest, 5 treatments, 1 posttest).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active rTMS With Conventional Therapy	Sham rTMS With Conventional Therapy
Arm/Group Description	20 minutes of active rTMS followed by conventional stroke therapy active rTMS: 10 minutes of real high-frequency (6-Hz) rTMS priming (total priming pulses = 600) plus 10 minutes of low-rate (1Hz) rTMS (total low-rate pulses = 600). conventional stroke therapy: conventional stroke therapy consisting of exercises and physical training	20 minutes of sham rTMS stimulation followed by conventional stroke therapy sham rTMS: 20 minutes of sham rTMS stimulation conventional stroke therapy: conventional stroke therapy consisting of exercises and physical training
Measure Participants	2	2
Mean (Standard Deviation) [percentage of change from baseline]	-23.0 (32.5)	0 (0)

2. Secondary Outcome

Title	Change in Finger Tracking Test
Description	This test involves placing a device on the hand that shows the changing angle of the finger joint on a computer screen as the joint is moved. The computer screen also shows a target line, such as a sine wave. At the start of the test, the computer screen cursor moves horizontally across the target and the subject moves the finger joint into extension or flexion to adjust the vertical position of the cursor to that it traces the target line as accurately as possible. The performance is quantified by calculating the root-mean-square error between the target line and the response line. This is converted into an Accuracy Index, which has a maximum value of 100% (perfect score). Negative values can occur and reach a value of -100%, signifying very poor performance. Typical scores for healthy range from 50-80%. Typical values in stroke range from -100 to +40%. Changes that are positive signify increased tracking accuracy at posttest compared to pretest, which would be an improvement.
Time Frame	Measured at pretest (day before treatments begin) and posttest (day following last treatment). Thus, 7 days of participation (1 pretest, 5 treatments, 1 posttest).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active rTMS With Conventional Therapy	Sham rTMS With Conventional Therapy
Arm/Group Description	20 minutes of active rTMS followed by conventional stroke therapy active rTMS: 10 minutes of real high-frequency (6-Hz) rTMS priming (total priming pulses = 600) plus 10 minutes of low-rate (1Hz) rTMS (total low-rate pulses = 600). conventional stroke therapy: conventional stroke therapy consisting of exercises and physical training	20 minutes of sham rTMS stimulation followed by conventional stroke therapy sham rTMS: 20 minutes of sham rTMS stimulation conventional stroke therapy: conventional stroke therapy consisting of exercises and physical training
Measure Participants	2	2
Mean (Standard Deviation) [units on a scale]	24.5 (25.2)	-13.8 (41.8)

3. Secondary Outcome

Title	Change in Motricity Index
Description	Measures strength in finger pinch, elbow flexion and arm abduction. 0 No pinch movement. 11 Slight movement of finger or thumb. 19 Able to grip the cube, but not hold it against gravity. 22 Able to grip and hold the cube against gravity, but not against a weak pull by examiner. The weighted score based on the ordinal 6 point scale 26 Able to grip and hold the cube against a weak pull, but weaker than the other side. 33 Normal pinch grip. For shoulder and elbow scoring is: 0 No movement. 9 Palpable contraction in muscle, but no movement. 14 Visible movement, but not full range and not against gravity. 19 Full range of movement against gravity but not against resistance. 25 Full movement against resistance, but weaker than the other side. 33 Normal power. Maximum total score is 99, minimum is 0. Changes that are positive signify improved strength at postte
Time Frame	Measured at pretest (day before treatments begin) and posttest (day following last treatment). Thus, 7 days of participation (1 pretest, 5 treatments, 1 posttest).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active rTMS With Conventional Therapy	Sham rTMS With Conventional Therapy
Arm/Group Description	20 minutes of active rTMS followed by conventional stroke therapy active rTMS: 10 minutes of real high-frequency (6-Hz) rTMS priming (total priming pulses = 600) plus 10 minutes of low-rate (1Hz) rTMS (total low-rate pulses = 600). conventional stroke therapy: conventional stroke therapy consisting of exercises and physical training	20 minutes of sham rTMS stimulation followed by conventional stroke therapy sham rTMS: 20 minutes of sham rTMS stimulation conventional stroke therapy: conventional stroke therapy consisting of exercises and physical training
Measure Participants	2	2
Mean (Standard Deviation) [units on a scale]	4 (5.7)	11 (0)

Adverse Events

Time Frame	1 year
Arm/Group Title	Active rTMS With Conventional Therapy		Sham rTMS With Conventional Therapy
Arm/Group Description	20 minutes of active rTMS followed by conventional stroke therapy active rTMS: 10 minutes of real high-frequency (6-Hz) rTMS priming (total priming pulses = 600) plus 10 minutes of low-rate (1Hz) rTMS (total low-rate pulses = 600). conventional stroke therapy: conventional stroke therapy consisting of exercises and physical training		20 minutes of sham rTMS stimulation followed by conventional stroke therapy sham rTMS: 20 minutes of sham rTMS stimulation conventional stroke therapy: conventional stroke therapy consisting of exercises and physical training
All Cause Mortality
	Active rTMS With Conventional Therapy		Sham rTMS With Conventional Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Active rTMS With Conventional Therapy		Sham rTMS With Conventional Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Active rTMS With Conventional Therapy		Sham rTMS With Conventional Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)

Limitations/Caveats

Enrollment of subjects was insufficient.

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.