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

Primary Purpose

Stroke

Status
Completed
Phase
Not Applicable
Locations
Hong Kong
Study Type
Interventional
Intervention
Theta burst stimulation (TBS)
Robot-assisted training
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, upper limb, metaplasticity, priming

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The Hong Kong Polytechnic University, Department of Rehabilitation Sciences

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Sham Comparator

Arm Label

cTBS + iTBS, in addition to robot-assisted training

Sham cTBS + iTBS, in addition to robot-assisted training

Sham cTBS + sham iTBS, in addition to robot-assisted training

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE)
FMA-UE is a standard upper limb motor impairment assessment for stroke survivors. FMA-UE assesses voluntary movement, reflex activity, grasp and coordination.
Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE)
FMA-UE is a standard upper limb motor impairment assessment for stroke survivors. FMA-UE assesses voluntary movement, reflex activity, grasp and coordination.
Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE)
FMA-UE is a standard upper limb motor impairment assessment for stroke survivors. FMA-UE assesses voluntary movement, reflex activity, grasp and coordination.
Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE)
FMA-UE is a standard upper limb motor impairment assessment for stroke survivors. FMA-UE assesses voluntary movement, reflex activity, grasp and coordination.
Action Research Arm Test (ARAT)
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.
Action Research Arm Test (ARAT)
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.
Action Research Arm Test (ARAT)
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.
Action Research Arm Test (ARAT)
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.

Secondary Outcome Measures

Sensorimotor event-related desynchronization
Electroencephalographical assessment for cortical activation induced by movement and mirror visual feedback-based observation of movement
Sensorimotor event-related desynchronization
Electroencephalographical assessment for cortical activation induced by movement and mirror visual feedback-based observation of movement
Mean velocity
Mean velocity is a quantified assessment for movement efficiency during robot-assisted training with Fourier M2 device.
Mean velocity
Mean velocity is a quantified assessment for movement efficiency during robot-assisted training with Fourier M2 device.

Full Information

First Posted
July 23, 2019
Last Updated
August 24, 2021
Sponsor
The Hong Kong Polytechnic University
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1. Study Identification

Unique Protocol Identification Number
NCT04034069
Brief Title
Effects of Priming Intermittent Theta Burst Stimulation on Upper Limb Motor Recovery After Stroke: A Randomized Controlled Trial
Official Title
Effects of Priming Intermittent Theta Burst Stimulation on Upper Limb Motor Recovery After Stroke: A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
September 9, 2019 (Actual)
Primary Completion Date
June 1, 2021 (Actual)
Study Completion Date
August 1, 2021 (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
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).
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.

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, upper limb, metaplasticity, priming

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
cTBS + iTBS, in addition to robot-assisted training
Arm Type
Experimental
Arm Description
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.
Arm Title
Sham cTBS + iTBS, in addition to robot-assisted training
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Sham cTBS + sham iTBS, in addition to robot-assisted training
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Theta burst stimulation (TBS)
Other Intervention Name(s)
Repetitive transcranial magnetic stimulation (rTMS)
Intervention Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Robot-assisted training
Intervention Description
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.
Primary Outcome Measure Information:
Title
Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE)
Description
FMA-UE is a standard upper limb motor impairment assessment for stroke survivors. FMA-UE assesses voluntary movement, reflex activity, grasp and coordination.
Time Frame
Baseline
Title
Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE)
Description
FMA-UE is a standard upper limb motor impairment assessment for stroke survivors. FMA-UE assesses voluntary movement, reflex activity, grasp and coordination.
Time Frame
1 week
Title
Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE)
Description
FMA-UE is a standard upper limb motor impairment assessment for stroke survivors. FMA-UE assesses voluntary movement, reflex activity, grasp and coordination.
Time Frame
2 weeks
Title
Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE)
Description
FMA-UE is a standard upper limb motor impairment assessment for stroke survivors. FMA-UE assesses voluntary movement, reflex activity, grasp and coordination.
Time Frame
2 weeks after the completion of training
Title
Action Research Arm Test (ARAT)
Description
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.
Time Frame
Baseline
Title
Action Research Arm Test (ARAT)
Description
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.
Time Frame
1 week
Title
Action Research Arm Test (ARAT)
Description
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.
Time Frame
2 week
Title
Action Research Arm Test (ARAT)
Description
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.
Time Frame
2 weeks after the completion of training
Secondary Outcome Measure Information:
Title
Sensorimotor event-related desynchronization
Description
Electroencephalographical assessment for cortical activation induced by movement and mirror visual feedback-based observation of movement
Time Frame
Baseline
Title
Sensorimotor event-related desynchronization
Description
Electroencephalographical assessment for cortical activation induced by movement and mirror visual feedback-based observation of movement
Time Frame
2 weeks
Title
Mean velocity
Description
Mean velocity is a quantified assessment for movement efficiency during robot-assisted training with Fourier M2 device.
Time Frame
Baseline
Title
Mean velocity
Description
Mean velocity is a quantified assessment for movement efficiency during robot-assisted training with Fourier M2 device.
Time Frame
2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
The Hong Kong Polytechnic University, Department of Rehabilitation Sciences
City
Hong Kong
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.
Citations:
PubMed Identifier
35317611
Citation
Zhang JJ, Bai Z, Fong KNK. Priming Intermittent Theta Burst Stimulation for Hemiparetic Upper Limb After Stroke: A Randomized Controlled Trial. Stroke. 2022 Jul;53(7):2171-2181. doi: 10.1161/STROKEAHA.121.037870. Epub 2022 Mar 23.
Results Reference
derived
PubMed Identifier
32152174
Citation
Zhang JJ, Fong KNK. Effects of priming intermittent theta burst stimulation on upper limb motor recovery after stroke: study protocol for a proof-of-concept randomised controlled trial. BMJ Open. 2020 Mar 8;10(3):e035348. doi: 10.1136/bmjopen-2019-035348.
Results Reference
derived

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

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