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

The Hong Kong Polytechnic University

Status: Completed

Conditions: Stroke

Treatments: Behavioral: Robot-assisted training; Device: Theta burst stimulation (TBS)

Study type: Interventional

Funder types: Other

Identifiers

NCT04034069

HSEARS20190718003

Details and patient eligibility

About

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).

Full 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.

Enrollment: 42 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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42 participants in 3 patient groups

cTBS + iTBS, in addition to robot-assisted training

Experimental group

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.

Treatment:

Device: Theta burst stimulation (TBS)

Behavioral: Robot-assisted training

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

Active Comparator group

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.

Treatment:

Device: Theta burst stimulation (TBS)

Behavioral: Robot-assisted training

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

Sham Comparator group

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.

Treatment:

Device: Theta burst stimulation (TBS)

Behavioral: Robot-assisted training