Clinical trial NCT02544503: Customized Cortical Stimulation Therapy in the Rehabilitation of Stroke Patients
Official title: Customized Cortical Stimulation Therapy in the Rehabilitation of Stroke Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Stroke
Keywords: Subacute stroke
Chronic stroke
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2015-09-09
Enrollment: 100
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to identify and establish how the area of the brain that controls motor function (motor cortex) of the non-affected hemisphere after stroke might serve as a new target for therapeutic interventions to improve motor performance after stroke.

Detailed description: It is well known that the motor area of one hemisphere of the brain (motor cortex) controls the movement of the opposite side of the body but the role of the motor cortex in the hemisphere spared by stroke (contralesional motor cortex) in motor performance during post stroke recovery is still unclear. It is also not clear whether the motor cortex of both hemispheres of the brain are involved, as movement becomes more complicated. Currently the role of the motor cortex on the same side of the body (referred to as ipsilateral motor cortex) in hand performance remains controversial. In most patients with stroke, only one side of the brain is affected by the stroke (affected hemisphere) resulting in weakness of half of the body opposite to the side of the stroke. Over the recent years, research has discovered that the side of the brain, that is spared by the stroke (non-affected hemisphere) may support recovery after stroke. However, there is also a question whether the non-affected hemisphere may interfere with the process of recovery. It is currently not known what factors influence the activity of non-affected hemisphere to either support or interfere with the recovery of stroke. A better understanding of those events is critical to development of optimal therapeutic strategies. For example, non-invasive stimulation of specific areas of the non-affected hemisphere may help to improve functional recovery following stroke. The objectives of this study are to define the factors that influence the activity in the non-affected hemisphere to either support or interfere with the recovery after stroke. The researchers will study the area of the brain that controls movements of the non-affected hemisphere as it relates to motor function post-stroke.

Transcranial magnetic stimulation (TMS) is a device that allows non-invasive stimulation of the brain. When the brain is stimulated repetitively at a very low rate and low intensity for about 15 minutes, the stimulated brain area becomes less active. This effect lasts 10 minutes and is called a "transient artificial lesion" as it mimics the effects of transiently interfering with the function of the stimulated brain area. The study includes experiments that first identify the extent of stroke and brain areas involved in a motor task using functional MRI of the brain and TMS. The researchers will then determine the functional role of the contralesional motor cortex by studying the effect of low frequency and high frequency repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) on interhemispheric inhibition (IHI) (resting and active) and motor cortex excitability (short interval intracortical excitability and corticospinal excitability) and behavior. The researchers will thereby also identify rTMS protocols that enhance motor performance in stroke patients.

In this study the researchers will conduct experiments using repetitive TMS to downregulate the activity of the motor area and measures its effect on activity of motor cortex of both hemispheres. In addition to enrolling participants who have had a stroke, the researchers will enroll healthy participants as this collected data will provide normative values for task related changes in M1s and their interactions - a prerequisite to studying abnormalities in stroke patients during motor recovery. The measurements and interventions will occur at two time points in all participants with stroke (1 and 6 months post-stroke). The data will be compared to the results of healthy age matched controls, assessed at a single time point.

Eligibility criteria: Inclusion Criteria for all Participants

* The ability to provide informed consent
* Ages 40 to 80 years old
* Male or female

Additional Inclusion Criteria for Stroke Patients:

* One cerebral ischemic infarction less than 1 month affecting the primary motor output system of the hand at a cortical (M1) level as defined by magnetic resonance imaging (MRI) of the brain
* Paresis of the hand for more than 3 days after their cerebral infarction

Additional Inclusion Criteria for Healthy Subjects:

* Normal MRI of the brain
* Normal neuropsychological testing
* Normal neurological examination

Exclusion Criteria for Stroke Patients:

* Neurological disorders other than stroke
* Aphasia that prevents following instructions or inability to communicate effectively with the study team
* Dementia
* Moderate or severe depression
* Contraindication to transcranial magnetic stimulation (TMS) and/or MRI
* Use of central nervous system (CNS) active drugs that block plasticity

Exclusion Criteria for Healthy Subjects:

* Neurological Disease
* Psychiatric Disease
* Use of CNS active drugs
* Contraindication to transcranial magnetic stimulation (TMS) and/or MRI

Primary outcomes:
measure: Motor Function Assessed by the Jebsen Test
timeFrame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
measure: Mean Motor Evoked Potential (MEP) Amplitudes Assessed by Stimulus Response Curve (SRC) of the Contralesional M1
timeFrame: 1 month post-stroke (subacute stroke) or single study visit for healthy controls, 6 months post-stroke (chronic stroke)
measure: Presence of MEP in Response to TMS of the Ipsilesional M1
timeFrame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
measure: Lesion Volume
timeFrame: 1 month post-stroke (subacute stroke)
measure: Corticospinal Tract (CST) Lesion
timeFrame: 1 month post-stroke (subacute stroke)
Secondary outcomes:
measure: Motor Function Assessed by Time to Complete the Wolf Motor Function Test (WMFT)
timeFrame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
measure: Motor Function Assessed by Grip Strength During the Wolf Motor Function Test (WMFT)
timeFrame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
measure: Use of Paretic Arm Assessed by the Motor Activity Log (MAL)
timeFrame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
measure: CST Subpathway Originating in M1 Lesion Load
timeFrame: 1 month post-stroke (subacute stroke)
measure: Primary Motor Cortex (M1) Activity, Assessed by Functional Magnetic Resonance Imaging (fMRI)
timeFrame: 1 month post-stroke (subacute stroke) or single study visit for healthy controls, 6 months post-stroke (chronic stroke)
measure: Short Interval Cortical Inhibition (SICI) Measured by Repeated Transcranial Magnetic Stimulation (rTMS)
timeFrame: 1 month post-stroke (subacute stroke) or single study visit for healthy controls, 6 months post-stroke (chronic stroke)
measure: Peak Velocity During Wrist Extension Movement
timeFrame: 1 month post-stroke (subacute stroke), 6 months post-stroke (chronic stroke)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Center for Rehabilitation Medicine
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
Study officials:
affiliation: Emory University
name: Cathrin Buetefisch, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: