Effects of Priming Intermittent Theta Burst Stimulation on Upper Limb Motor Recovery After Stroke: A Randomized Controlled Trial

August 24, 2021 updated by: Kenneth N. K. Fong, The Hong Kong Polytechnic University
The aim of this study is to investigate the effects of intermittent theta burst stimulation primed with continous theta burst stimulation (cTBS), on top of a standard robot-assisted training (RAT) on improving the upper limb motor functions of stroke survivors and to explore potential sensorimotor neuroplasticity with electroencephalography (EEG).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Intermittent theta burst stimulation (iTBS) delivered to the affected primary motor cortex (M1) appears to enhance the brain response to rehabilitative intervention in patients with stroke. However, its clinical utility is highly affected by the response variability. New evidence has reported that preceding iTBS with a priming session of continuous theta burst stimulation (cTBS), may stabilize and even boost the facilitatory effect of iTBS on the stimulated M1, via metaplasticity. The aim of this study is to investigate the effects of iTBS primed with cTBS, on top of a standard robot-assisted training (RAT) on improving the upper limb motor functions of patients with chronic stroke and to explore potential sensorimotor neuroplasticity with electroencephalography (EEG). A three-arm randomized controlled trial (RCT) will be performed with an estimated total of 36 patients with subacute or chronic stroke. All participants will be randomly allocated to receive 10-session intervention of different TBS protocols (i.e., cTBS+iTBS, sham cTBS+iTBS and sham cTBS+sham iTBS), delivered for 3-5 sessions per week, lasting for 2-3 weeks. All participants will receive a 60-minute standard RAT after each stimulation session. Primary outcome will be Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE). Secondary outcomes will be Action Research Arm Test (ARAT), kinematic outcomes generated during RAT as well as and EEG.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • The Hong Kong Polytechnic University, Department of Rehabilitation Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • with a diagnosis of a unilateral ischemic or hemorrhagic stroke;
  • with stroke onset more than 6 months;
  • from 18 to 75 years old;
  • with mild to moderate impairment of upper limb functions due to stroke, measured using the Hong Kong Version of the Functional Test for the Hemiplegic Upper Extremity (FTHUE-HK) from level 2 to level 7;
  • be able to understand verbal instruction and follow one-step commands;
  • be able to give informed consent to participate;

Exclusion Criteria:

  • any contraindications to rTMS/TBS, such as unstable medical condition, history of epileptic seizures, metal implants in vivo (eg, pacemaker, artificial cochlear, and implant brain stimulator), and a history of receiving craniotomy;
  • previous diagnosis of any neurological disease excluding stroke;
  • presence of any sign of cognitive problems (Abbreviated mental test Hong Kong version < 6/10);
  • patients with extreme spasticity in any hemiplegic upper limb joint (Modified Ashworth score > 2) or severe pain that hinder the upper limb motor training;
  • with other notable impairment of the upper limb affected by stroke, eg, recent fracture, severe osteoarthritis, congenital upper limb deformity
  • any sign of anxiety or depression, as assessed by the Hospital Anxiety and Depression Scale.
  • concurrent participation in an upper limb rehabilitation program or a medicine trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: cTBS + iTBS, in addition to robot-assisted training
Participants will receive 10-session intervention of priming iTBS protocol (cTBS followed by iTBS, with an interval of 10 minutes). The stimulation will be delivered 3-5 sessions per week, lasting for 2-3 weeks. Participants will receive a 60-minute standard robot-assisted training after each stimulation session.
Device: Theta burst stimulation (TBS)
Theta burst stimulation (TBS) is a potent form of repetitive transcranial magnetic stimulation (rTMS). Standard 600-pulse intermittent theta burst stimulation (iTBS) can enhance the corticomotor excitability, whereas standard 600-pulse continuous theta burst stimulation (cTBS) can suppress the corticomotor excitability. Sham stimulation uses an extreme low stimulation intensity which will not influence with corticomotor excitability. In the present study, real stimulation will be delivered in an intensity of 70% individual resting motor threshold while sham stimulation will be delivered in an intensity of 20% individual resting motor threshold.
Other Names:
  • Repetitive transcranial magnetic stimulation (rTMS)
Behavioral: Robot-assisted training
Fourier M2 upper limb rehabilitation robot (Fourier Intelligence Co. Ltd., Shanghai, China), will be used for upper limb proximal joints training. Fourier M2 upper limb rehab robot is an end-effector robot-assisted device. The device targets (1) flexion and extension of shoulder joint, (2) flexion and extension of elbow, (3) internal and external rotation of shoulder joint, and (4) abduction and adduction of shoulder joint, supported by tailored interactive TV games in the device. HandyRehab hand robot (Zunosaki Company Ltd., Hong Kong SAR) will be used for upper limb distal joints training. It is an exoskeleton over the hand which provides power-driven extension and grasping force to the fingers and thumb in order to assist the patient to open and close the paretic hand by means of surface electromyography-triggered from the signals through the forearm extensors and flexors.
Active Comparator: Sham cTBS + iTBS, in addition to robot-assisted training
Participants will receive 10-session intervention of non-primed, standard iTBS (sham cTBS followed by iTBS, with an interval of 10 minutes). The stimulation will be delivered 3-5 sessions per week, lasting for 2-3 weeks. Participants will receive a 60-minute standard robot-assisted training after each stimulation session.
Device: Theta burst stimulation (TBS)
Theta burst stimulation (TBS) is a potent form of repetitive transcranial magnetic stimulation (rTMS). Standard 600-pulse intermittent theta burst stimulation (iTBS) can enhance the corticomotor excitability, whereas standard 600-pulse continuous theta burst stimulation (cTBS) can suppress the corticomotor excitability. Sham stimulation uses an extreme low stimulation intensity which will not influence with corticomotor excitability. In the present study, real stimulation will be delivered in an intensity of 70% individual resting motor threshold while sham stimulation will be delivered in an intensity of 20% individual resting motor threshold.
Other Names:
  • Repetitive transcranial magnetic stimulation (rTMS)
Behavioral: Robot-assisted training
Fourier M2 upper limb rehabilitation robot (Fourier Intelligence Co. Ltd., Shanghai, China), will be used for upper limb proximal joints training. Fourier M2 upper limb rehab robot is an end-effector robot-assisted device. The device targets (1) flexion and extension of shoulder joint, (2) flexion and extension of elbow, (3) internal and external rotation of shoulder joint, and (4) abduction and adduction of shoulder joint, supported by tailored interactive TV games in the device. HandyRehab hand robot (Zunosaki Company Ltd., Hong Kong SAR) will be used for upper limb distal joints training. It is an exoskeleton over the hand which provides power-driven extension and grasping force to the fingers and thumb in order to assist the patient to open and close the paretic hand by means of surface electromyography-triggered from the signals through the forearm extensors and flexors.
Sham Comparator: Sham cTBS + sham iTBS, in addition to robot-assisted training
Participants will receive 10-session intervention of sham stimulation (sham cTBS followed by sham iTBS, with an interval of 10 minutes). The stimulation will be delivered 3-5 sessions per week, lasting for 2-3 weeks. Participants will receive a 60-minute standard robot-assisted training after each stimulation session.
Device: Theta burst stimulation (TBS)
Theta burst stimulation (TBS) is a potent form of repetitive transcranial magnetic stimulation (rTMS). Standard 600-pulse intermittent theta burst stimulation (iTBS) can enhance the corticomotor excitability, whereas standard 600-pulse continuous theta burst stimulation (cTBS) can suppress the corticomotor excitability. Sham stimulation uses an extreme low stimulation intensity which will not influence with corticomotor excitability. In the present study, real stimulation will be delivered in an intensity of 70% individual resting motor threshold while sham stimulation will be delivered in an intensity of 20% individual resting motor threshold.
Other Names:
  • Repetitive transcranial magnetic stimulation (rTMS)
Behavioral: Robot-assisted training
Fourier M2 upper limb rehabilitation robot (Fourier Intelligence Co. Ltd., Shanghai, China), will be used for upper limb proximal joints training. Fourier M2 upper limb rehab robot is an end-effector robot-assisted device. The device targets (1) flexion and extension of shoulder joint, (2) flexion and extension of elbow, (3) internal and external rotation of shoulder joint, and (4) abduction and adduction of shoulder joint, supported by tailored interactive TV games in the device. HandyRehab hand robot (Zunosaki Company Ltd., Hong Kong SAR) will be used for upper limb distal joints training. It is an exoskeleton over the hand which provides power-driven extension and grasping force to the fingers and thumb in order to assist the patient to open and close the paretic hand by means of surface electromyography-triggered from the signals through the forearm extensors and flexors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Action Research Arm Test (ARAT)
Time Frame: Baseline
ARAT is a standard upper limb functional performance assessment for stroke survivors. ARAT assesses a patient's ability to handle objects differing in size, weight and shape. ARAT consists of 19 items grouped into four subscales: grasp, grip, pinch, and gross movement.
Baseline
Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE)
Time Frame: Baseline
FMA-UE is a standard upper limb motor impairment assessment for stroke survivors. FMA-UE assesses voluntary movement, reflex activity, grasp and coordination.
Baseline
Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE)
Time Frame: 1 week
FMA-UE is a standard upper limb motor impairment assessment for stroke survivors. FMA-UE assesses voluntary movement, reflex activity, grasp and coordination.
1 week
Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE)
Time Frame: 2 weeks
FMA-UE is a standard upper limb motor impairment assessment for stroke survivors. FMA-UE assesses voluntary movement, reflex activity, grasp and coordination.
2 weeks
Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE)
Time Frame: 2 weeks after the completion of training
FMA-UE is a standard upper limb motor impairment assessment for stroke survivors. FMA-UE assesses voluntary movement, reflex activity, grasp and coordination.
2 weeks after the completion of training
Action Research Arm Test (ARAT)
Time Frame: 1 week
ARAT is a standard upper limb functional performance assessment for stroke survivors. ARAT assesses a patient's ability to handle objects differing in size, weight and shape. ARAT consists of 19 items grouped into four subscales: grasp, grip, pinch, and gross movement.
1 week
Action Research Arm Test (ARAT)
Time Frame: 2 week
ARAT is a standard upper limb functional performance assessment for stroke survivors. ARAT assesses a patient's ability to handle objects differing in size, weight and shape. ARAT consists of 19 items grouped into four subscales: grasp, grip, pinch, and gross movement.
2 week
Action Research Arm Test (ARAT)
Time Frame: 2 weeks after the completion of training
ARAT is a standard upper limb functional performance assessment for stroke survivors. ARAT assesses a patient's ability to handle objects differing in size, weight and shape. ARAT consists of 19 items grouped into four subscales: grasp, grip, pinch, and gross movement.
2 weeks after the completion of training

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensorimotor event-related desynchronization
Time Frame: Baseline
Electroencephalographical assessment for cortical activation induced by movement and mirror visual feedback-based observation of movement
Baseline
Sensorimotor event-related desynchronization
Time Frame: 2 weeks
Electroencephalographical assessment for cortical activation induced by movement and mirror visual feedback-based observation of movement
2 weeks
Mean velocity
Time Frame: Baseline
Mean velocity is a quantified assessment for movement efficiency during robot-assisted training with Fourier M2 device.
Baseline
Mean velocity
Time Frame: 2 weeks
Mean velocity is a quantified assessment for movement efficiency during robot-assisted training with Fourier M2 device.
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Hong Kong Polytechnic University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 9, 2019

Primary Completion (Actual)

June 1, 2021

Study Completion (Actual)

August 1, 2021

Study Registration Dates

First Submitted

July 23, 2019

First Submitted That Met QC Criteria

July 24, 2019

First Posted (Actual)

July 26, 2019

Study Record Updates

Last Update Posted (Actual)

August 30, 2021

Last Update Submitted That Met QC Criteria

August 24, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HSEARS20190718003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The data will be shared for research purpose upon reasonable request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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