Repetitive Transcranial Magnetic Stimulation Use in Acute Stroke

Stroke Clinical Trial

Official title:

Real vs Sham rTMS Combined With Conventional Therapy in Acute Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01922986
• Other study ID #: Acute_rTMS
• Status: Completed
• Phase: N/A
• First received: July 26, 2013
• Last updated: December 4, 2015
• Start date: September 2013
• Est. completion date: March 2015

Study information

• Verified date: December 2015
• Source: University of Minnesota - Clinical and Translational Science Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardUnited States: Data and Safety Monitoring Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stroke

Intervention

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).
• sham rTMS
20 minutes of sham rTMS stimulation

Behavioral:
• conventional stroke therapy
conventional stroke therapy consisting of exercises and physical training

Locations

Country	Name	City	State
United States	Courage Kenny Rehabilitation Institute	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota - Clinical and Translational Science Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Jebsen Taylor Hand Function test	This is a test of function in daily tasks using the hand.	Measured at pretest (day before treatments begin) and posttest (day following last treatment). Thus, 7 days of participation (1 pretest, 5 treatments, 1 posttest).	No
Secondary	Change in finger tracking test	test of finger movement ability	Measured at pretest (day before treatments begin) and posttest (day following last treatment). Thus, 7 days of participation (1 pretest, 5 treatments, 1 posttest).	No
Secondary	Change in Motricity Index	test of hand strength	Measured at pretest (day before treatments begin) and posttest (day following last treatment). Thus, 7 days of participation (1 pretest, 5 treatments, 1 posttest).	No