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The Immediate Effects of Intermittent Theta Burst Stimulation on Intracortical Excitability of the Primary Motor Cortex in Patients With Chronic Stroke

Primary Purpose

Stroke

Status
Completed
Phase
Not Applicable
Locations
Hong Kong
Study Type
Interventional
Intervention
Intermittent theta burst stimulation (iTBS)
Sham intermittent theta burst stimulation (iTBS)
Sponsored by
The Hong Kong Polytechnic University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke focused on measuring stroke, theta burst stimulation, transcranial magnetic stimulation-evoked potentials, intracortical inhibition, cortical excitability

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. suffered from first-ever, ischemic or hemorrhagic, unilateral stroke, verified by neuroimaging examinations such as CT or MRI.
  2. detectable motor evoked potentials from the affected first dorsal interosseous muscle;
  3. provided written informed consent.

Exclusion Criteria:

  1. had any contraindication to transcranial magnetic stimulation;
  2. had a known neurological disease excluding stroke, or psychiatric disease;
  3. were using a psychostimulant, sedative, antidepressant, or antiepileptic medication.

Sites / Locations

  • Kenneth FONG

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

A single-session intermittent theta burst stimulation (iTBS)

A single-session sham intermittent theta burst stimulation (iTBS)

Arm Description

The classical 600-pulse iTBS protocol is delivered to the motor hotspot over the ipsilesional hemisphere.

The sham stimulation is the same as that of iTBS, but the coil is placed five centimeters away from the scalp.

Outcomes

Primary Outcome Measures

Transcranial magnetic stimulation-evoked potential
Single pulses evoked an initial response in electroencephalogram, followed by a series of time- and phase-locked positive and negative deflections which could spread to the connected brain areas. The evoked potential is called transcranial magnetic stimulation-evoked potential.
Transcranial magnetic stimulation-evoked potential
Single pulses evoked an initial response in electroencephalogram, followed by a series of time- and phase-locked positive and negative deflections which could spread to the connected brain areas. The evoked potential is called transcranial magnetic stimulation-evoked potential.
Motor evoked potential (MEP)
Single TMS pulses with suprathreshold intensity (120% of resting motor threshold of the stimulated cortex) applied to the primary motor cortex (M1) can produce recordable MEPs in contralateral muscles; additionally, the peak-to-peak amplitude of MEPs can be used to represent the corticospinal excitability
Motor evoked potential (MEP)
Single TMS pulses with suprathreshold intensity (120% of resting motor threshold of the stimulated cortex) applied to the primary motor cortex (M1) can produce recordable MEPs in contralateral muscles; additionally, the peak-to-peak amplitude of MEPs can be used to represent the corticospinal excitability

Secondary Outcome Measures

Cortical silent period
The cortical silent period (cSP) is a protocol measuring the intracortical inhibition, in which suprathreshold test pulses (120% of resting motor threshold of the stimulated cortex) are applied to the contralateral M1, while participants sustain 30% maximum voluntary contraction. Specifically, cSP refers to the interruption of background electromyographic (EMG) activity after the TMS pulse.
Cortical silent period
The cortical silent period (cSP) is a protocol measuring the intracortical inhibition, in which suprathreshold test pulses (120% of resting motor threshold of the stimulated cortex) are applied to the contralateral M1, while participants sustain 30% maximum voluntary contraction. Specifically, cSP refers to the interruption of background electromyographic (EMG) activity after the TMS pulse.
Short-interval intracortical inhibition
Short-interval intracortical inhibition (SICI) is a form of paired-pulse protocol, in which a subthreshold conditioning pulse is delivered 2 ms before a suprathreshold test pulse. Theoretically, the amplitude of motor-evoked potentials (MEPs) evoked by a test pulse at a given intensity is suppressed compared with that evoked by a single pulse at the same intensity. Eight trials are recorded, with inter-trial intervals ranging from 4 s to 5 s. The intensity of test pulses is fixed at 120% of the resting motor threshold, and the intensity of the conditioning pulse is set at 80% of the resting motor threshold. The result of SICI is expressed as the ratio of a paired-pulse MEP amplitude to a single-pulse MEP amplitude.
Short-interval intracortical inhibition
Short-interval intracortical inhibition (SICI) is a form of paired-pulse protocol, in which a subthreshold conditioning pulse is delivered 2 ms before a suprathreshold test pulse. Theoretically, the amplitude of motor-evoked potentials (MEPs) evoked by a test pulse at a given intensity is suppressed compared with that evoked by a single pulse at the same intensity. Eight trials are recorded, with inter-trial intervals ranging from 4 s to 5 s. The intensity of test pulses is fixed at 120% of the resting motor threshold, and the intensity of the conditioning pulse is set at 80% of the resting motor threshold. The result of SICI is expressed as the ratio of a paired-pulse MEP amplitude to a single-pulse MEP amplitude.
Intracortical facilitation
The setups for the intensity of intracortical facilitation (ICF) are almost the same as those for SICI; however, the interstimulus interval is longer, 10 ms. Eight trials are recorded, with inter-trial intervals ranging from 4 s to 5 s. The intensity of test pulses is fixed at 120% of the resting motor threshold, and the intensity of the conditioning pulse is set at 80% of the resting motor threshold. The result of ICF is expressed as the ratio of a paired-pulse MEP amplitude to a single-pulse MEP amplitude.
Intracortical facilitation
The setups for the intensity of intracortical facilitation (ICF) are almost the same as those for SICI; however, the interstimulus interval is longer, 10 ms. Eight trials are recorded, with inter-trial intervals ranging from 4 s to 5 s. The intensity of test pulses is fixed at 120% of the resting motor threshold, and the intensity of the conditioning pulse is set at 80% of the resting motor threshold. The result of ICF is expressed as the ratio of a paired-pulse MEP amplitude to a single-pulse MEP amplitude.

Full Information

First Posted
August 18, 2022
Last Updated
August 18, 2022
Sponsor
The Hong Kong Polytechnic University
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1. Study Identification

Unique Protocol Identification Number
NCT05509686
Brief Title
The Immediate Effects of Intermittent Theta Burst Stimulation on Intracortical Excitability of the Primary Motor Cortex in Patients With Chronic Stroke
Official Title
The Immediate Effects of Intermittent Theta Burst Stimulation on Intracortical Excitability of the Primary Motor Cortex in Patients With Chronic Stroke: A Concurrent TMS-EEG Sham-controlled Crossover Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
July 15, 2020 (Actual)
Primary Completion Date
July 30, 2021 (Actual)
Study Completion Date
May 15, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Hong Kong Polytechnic University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is to investigate the immediate effects of intermittent theta burst stimulation (iTBS) on intracortical excitatory and inhibitory circuits, neural connectivity, and network properties in patients with chronic stroke, using transcranial magnetic stimulation and electroencephalogram (TMS-EEG) and TMS-electromyography (EMG) and approaches.
Detailed Description
The neurophysiological effect of intermittent theta burst stimulation (iTBS) has been examined with TMS-electromyography (EMG)-based outcomes in healthy people; however, its effects in intracortical excitability and inhibition are largely unknown in patients with stroke. Concurrent transcranial magnetic stimulation and electroencephalogram (TMS-EEG) recording can be used to investigate both intracortical excitatory and inhibitory circuits of the primary motor cortex (M1) and the property of brain networks. This study is to investigate the immediate effects of iTBS on intracortical excitatory and inhibitory circuits, neural connectivity, and network properties in patients with chronic stroke, using TMS-EEG and TMS-EMG approaches. In this randomized, sham-controlled, crossover study, 21 patients with chronic stroke receive two separate stimulation conditions: a single-session iTBS or sham stimulation applied to the ipsilesional M1, in two separate visits, with a washout period of five to seven days between the two visits after crossover. A battery of TMS-EMG and TMS-EEG measurements are taken before and immediately after stimulation during the visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke
Keywords
stroke, theta burst stimulation, transcranial magnetic stimulation-evoked potentials, intracortical inhibition, cortical excitability

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A single-session intermittent theta burst stimulation (iTBS)
Arm Type
Experimental
Arm Description
The classical 600-pulse iTBS protocol is delivered to the motor hotspot over the ipsilesional hemisphere.
Arm Title
A single-session sham intermittent theta burst stimulation (iTBS)
Arm Type
Sham Comparator
Arm Description
The sham stimulation is the same as that of iTBS, but the coil is placed five centimeters away from the scalp.
Intervention Type
Device
Intervention Name(s)
Intermittent theta burst stimulation (iTBS)
Intervention Description
A single-session standard 600-pulse intermittent theta burst stimulation (iTBS) is applied to the ipsilesional primary motor cortex.
Intervention Type
Device
Intervention Name(s)
Sham intermittent theta burst stimulation (iTBS)
Intervention Description
The sham stimulation is the same as that of iTBS, but the coil is placed five centimeters away from the scalp. Electrical field simulation shows that the setups for sham stimulation would not induce any valid cortical activation.
Primary Outcome Measure Information:
Title
Transcranial magnetic stimulation-evoked potential
Description
Single pulses evoked an initial response in electroencephalogram, followed by a series of time- and phase-locked positive and negative deflections which could spread to the connected brain areas. The evoked potential is called transcranial magnetic stimulation-evoked potential.
Time Frame
Baseline (before iTBS stimulation)
Title
Transcranial magnetic stimulation-evoked potential
Description
Single pulses evoked an initial response in electroencephalogram, followed by a series of time- and phase-locked positive and negative deflections which could spread to the connected brain areas. The evoked potential is called transcranial magnetic stimulation-evoked potential.
Time Frame
10 minutes after a single-session iTBS stimulation
Title
Motor evoked potential (MEP)
Description
Single TMS pulses with suprathreshold intensity (120% of resting motor threshold of the stimulated cortex) applied to the primary motor cortex (M1) can produce recordable MEPs in contralateral muscles; additionally, the peak-to-peak amplitude of MEPs can be used to represent the corticospinal excitability
Time Frame
Baseline (before iTBS stimulation)
Title
Motor evoked potential (MEP)
Description
Single TMS pulses with suprathreshold intensity (120% of resting motor threshold of the stimulated cortex) applied to the primary motor cortex (M1) can produce recordable MEPs in contralateral muscles; additionally, the peak-to-peak amplitude of MEPs can be used to represent the corticospinal excitability
Time Frame
10 minutes after a single-session iTBS stimulation
Secondary Outcome Measure Information:
Title
Cortical silent period
Description
The cortical silent period (cSP) is a protocol measuring the intracortical inhibition, in which suprathreshold test pulses (120% of resting motor threshold of the stimulated cortex) are applied to the contralateral M1, while participants sustain 30% maximum voluntary contraction. Specifically, cSP refers to the interruption of background electromyographic (EMG) activity after the TMS pulse.
Time Frame
Baseline (before iTBS stimulation)
Title
Cortical silent period
Description
The cortical silent period (cSP) is a protocol measuring the intracortical inhibition, in which suprathreshold test pulses (120% of resting motor threshold of the stimulated cortex) are applied to the contralateral M1, while participants sustain 30% maximum voluntary contraction. Specifically, cSP refers to the interruption of background electromyographic (EMG) activity after the TMS pulse.
Time Frame
10 minutes after a single-session iTBS stimulation
Title
Short-interval intracortical inhibition
Description
Short-interval intracortical inhibition (SICI) is a form of paired-pulse protocol, in which a subthreshold conditioning pulse is delivered 2 ms before a suprathreshold test pulse. Theoretically, the amplitude of motor-evoked potentials (MEPs) evoked by a test pulse at a given intensity is suppressed compared with that evoked by a single pulse at the same intensity. Eight trials are recorded, with inter-trial intervals ranging from 4 s to 5 s. The intensity of test pulses is fixed at 120% of the resting motor threshold, and the intensity of the conditioning pulse is set at 80% of the resting motor threshold. The result of SICI is expressed as the ratio of a paired-pulse MEP amplitude to a single-pulse MEP amplitude.
Time Frame
Baseline (before iTBS stimulation)
Title
Short-interval intracortical inhibition
Description
Short-interval intracortical inhibition (SICI) is a form of paired-pulse protocol, in which a subthreshold conditioning pulse is delivered 2 ms before a suprathreshold test pulse. Theoretically, the amplitude of motor-evoked potentials (MEPs) evoked by a test pulse at a given intensity is suppressed compared with that evoked by a single pulse at the same intensity. Eight trials are recorded, with inter-trial intervals ranging from 4 s to 5 s. The intensity of test pulses is fixed at 120% of the resting motor threshold, and the intensity of the conditioning pulse is set at 80% of the resting motor threshold. The result of SICI is expressed as the ratio of a paired-pulse MEP amplitude to a single-pulse MEP amplitude.
Time Frame
10 minutes after a single-session iTBS stimulation
Title
Intracortical facilitation
Description
The setups for the intensity of intracortical facilitation (ICF) are almost the same as those for SICI; however, the interstimulus interval is longer, 10 ms. Eight trials are recorded, with inter-trial intervals ranging from 4 s to 5 s. The intensity of test pulses is fixed at 120% of the resting motor threshold, and the intensity of the conditioning pulse is set at 80% of the resting motor threshold. The result of ICF is expressed as the ratio of a paired-pulse MEP amplitude to a single-pulse MEP amplitude.
Time Frame
Baseline (before iTBS stimulation)
Title
Intracortical facilitation
Description
The setups for the intensity of intracortical facilitation (ICF) are almost the same as those for SICI; however, the interstimulus interval is longer, 10 ms. Eight trials are recorded, with inter-trial intervals ranging from 4 s to 5 s. The intensity of test pulses is fixed at 120% of the resting motor threshold, and the intensity of the conditioning pulse is set at 80% of the resting motor threshold. The result of ICF is expressed as the ratio of a paired-pulse MEP amplitude to a single-pulse MEP amplitude.
Time Frame
10 minutes after a single-session iTBS stimulation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: suffered from first-ever, ischemic or hemorrhagic, unilateral stroke, verified by neuroimaging examinations such as CT or MRI. detectable motor evoked potentials from the affected first dorsal interosseous muscle; provided written informed consent. Exclusion Criteria: had any contraindication to transcranial magnetic stimulation; had a known neurological disease excluding stroke, or psychiatric disease; were using a psychostimulant, sedative, antidepressant, or antiepileptic medication.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kenneth Fong, PhD
Organizational Affiliation
Hong Kong Polytechnic University, QT517, Hung Hom
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kenneth FONG
City
Hong Kong
ZIP/Postal Code
000000
Country
Hong Kong

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
The data will be shared for research purpose upon reasonable request.

Learn more about this trial

The Immediate Effects of Intermittent Theta Burst Stimulation on Intracortical Excitability of the Primary Motor Cortex in Patients With Chronic Stroke

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