Customized Cortical Stimulation Therapy in the Rehabilitation of Stroke Patients

NCT ID: NCT02544503

Last Updated: 2023-08-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-05
• Study Completion Date: 2021-02-04

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.

Conditions

Stroke

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Stroke Patients

Subjects will undergo single pulse transcranial magnetic stimulation (TMS), paired pulse transcranial stimulation (ppTMS), and low frequency repetitive transcranial magnetic stimulation (rTMS) at one month and six months post stroke.

Group Type: EXPERIMENTAL

Single-pulse Transcranial Magnetic Stimulation (TMS)

Intervention Type: DEVICE

Single-pulse Transcranial Magnetic Stimulation (TMS) is a brief magnetic pulse that is applied through a coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Single-pulse transcranial magnetic stimulation (TMS) will be administered at study visits.

Paired-pulse Transcranial Magnetic Stimulation (ppTMS)

Intervention Type: DEVICE

Paired-pulse Transcranial Magnetic Stimulation (ppTMS) is two brief sequential magnetic pulses that are applied through a coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Paired-pulse transcranial magnetic stimulation (ppTMS) will be administered at study visits.

Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS)

Intervention Type: DEVICE

Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) is a sequence of brief magnetic pulses that are applied at 0.1 Hz frequency at low intensity through an air-cooled coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Low-frequency repetitive transcranial magnetic stimulation (rTMS) will be administered at study visits.

Sham Motor Cortex Stimulation

Intervention Type: DEVICE

Sham motor cortex stimulation will be applied at study visits.

Healthy Controls

Subjects will undergo single pulse transcranial magnetic stimulation (TMS), paired pulse transcranial stimulation (ppTMS), and low frequency repetitive transcranial magnetic stimulation (rTMS) at one month and six months.

Group Type: ACTIVE_COMPARATOR

Single-pulse Transcranial Magnetic Stimulation (TMS)

Intervention Type: DEVICE

Single-pulse Transcranial Magnetic Stimulation (TMS) is a brief magnetic pulse that is applied through a coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Single-pulse transcranial magnetic stimulation (TMS) will be administered at study visits.

Paired-pulse Transcranial Magnetic Stimulation (ppTMS)

Intervention Type: DEVICE

Paired-pulse Transcranial Magnetic Stimulation (ppTMS) is two brief sequential magnetic pulses that are applied through a coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Paired-pulse transcranial magnetic stimulation (ppTMS) will be administered at study visits.

Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS)

Intervention Type: DEVICE

Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) is a sequence of brief magnetic pulses that are applied at 0.1 Hz frequency at low intensity through an air-cooled coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Low-frequency repetitive transcranial magnetic stimulation (rTMS) will be administered at study visits.

Sham Motor Cortex Stimulation

Intervention Type: DEVICE

Sham motor cortex stimulation will be applied at study visits.

Interventions

Single-pulse Transcranial Magnetic Stimulation (TMS)

Single-pulse Transcranial Magnetic Stimulation (TMS) is a brief magnetic pulse that is applied through a coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Single-pulse transcranial magnetic stimulation (TMS) will be administered at study visits.

Intervention Type: DEVICE

Paired-pulse Transcranial Magnetic Stimulation (ppTMS)

Paired-pulse Transcranial Magnetic Stimulation (ppTMS) is two brief sequential magnetic pulses that are applied through a coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Paired-pulse transcranial magnetic stimulation (ppTMS) will be administered at study visits.

Intervention Type: DEVICE

Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS)

Low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) is a sequence of brief magnetic pulses that are applied at 0.1 Hz frequency at low intensity through an air-cooled coil to the section of the head that overlays the motor cortex of the brain. Subjects will be comfortably seated in a dental chair surrounded by a frame that carries a coil holder to assist with the application of TMS to the brain. Low-frequency repetitive transcranial magnetic stimulation (rTMS) will be administered at study visits.

Intervention Type: DEVICE

Sham Motor Cortex Stimulation

Sham motor cortex stimulation will be applied at study visits.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

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

• 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

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

Exclusion Criteria

• 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

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Cathrin Buetefisch

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cathrin Buetefisch, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Center for Rehabilitation Medicine

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Countries

United States

References

Wischnewski M, Edwards L, Revill KP, Drake D, Hobbs G, Buetefisch CM. Intensity-Dependent Effects of Low-Frequency Subthreshold rTMS on Primary Motor Cortex Excitability and Interhemispheric Inhibition in Elderly Participants: A Randomized Trial. Neurorehabil Neural Repair. 2025 Jan;39(1):58-73. doi: 10.1177/15459683241292615. Epub 2024 Oct 27.

Reference Type: DERIVED

PMID: 39462433 (View on PubMed)

Buetefisch CM, Haut MW, Revill KP, Shaeffer S, Edwards L, Barany DA, Belagaje SR, Nahab F, Shenvi N, Easley K. Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization. Neurorehabil Neural Repair. 2023 Feb-Mar;37(2-3):119-130. doi: 10.1177/15459683231152816. Epub 2023 Feb 14.

Reference Type: DERIVED

PMID: 36786394 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01NS090677

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00081238

Identifier Type: -

Identifier Source: org_study_id