Condition category
Circulatory System
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Ms Ulrike Hammerbeck


Contact details

Institute of Neurology
Queen Square London
Queen Square
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number

3279; G0401353

Study information

Scientific title

Enhancing the effect of physical therapy for motor impairment after stroke with Theta Burst Stimulation


TBS Study

Study hypothesis

In this study we plan to investigate whether brain stimulation can be used as an add-on treatment to consolidate the benefit from patterned upper limb physiotherapy and induce further hand motor improvement in chronic stroke patients.

To stimulate the brain we plan to use Theta Burst Stimulation (TBS), a novel paradigm of repetitive transcranial magnetic stimulation (TMS), aiming to increase cortical excitability of the affected (ipsilesional) hemisphere.

According to evidence so far, we believe that increased ipsilesional excitability can be achieved by:
1. Direct facilitation of the affected hemisphere (ipsilesional facilitation)
2. Inhibition of the unaffected hemisphere (contralesional inhibition)

Primary aim:
To investigate whether daily treatment with TBS followed by patterned physical therapy for a period of two weeks can lead to significant and sustained improvement of hand motor behavior in chronic stroke patients.

Secondary aims:
1. To study the physiological correlates of the potential behavioral gains
2. To identify physiological predictors of likelihood of response to the proposed intervention, so that appropriate patients may be targeted in future trials

Physiological correlates will be studied using TMS and functional magentic resonance imaging (fMRI) as detailed below.

Ethics approval

NHNN and ION Joint Research Ethics Committee approved on the 25/02/2005 (ref: 04/Q0512/108)

Study design

Randomised interventional treatment trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Topic: Stroke Research Network; Subtopic: Rehabilitation; Disease: Therapy type


Physical therapy (physiotherapy):
The protocol for physical therapy has been developed in collaboration with the therapy services department at the National Hospital for Neurology and Neurosurgery. It expands upon previous protocols by ensuring the equivalence of task intensity, repetition rate and verbal feedback across subjects. Treatment will be task oriented and individualised based on the findings of a questionnaire about current functional difficulties and an objective examination.

Theta Burst Stimulation:
TMS is a well tolerated method of stimulating the human cortex through the intact scalp. We will employ a new pattern of repetitive TMS called Theta Burst Stimulation (TBS). Each burst consists of 3 low intensity (80% aMT, see further on) stimuli, repeating at high frequency (50Hz). Bursts are repeating at 5Hz, i.e. the "theta" rhythm of the EEG. A total of 15 pulses are delivered per second. TBS effect on corticospinal excitability can be either inhibitory of facilitatory, depending on the pattern.

Follow up length: 3 months
Study entry: single randomisation only

Intervention type



Not Applicable

Drug names

Primary outcome measure

Action Research Arm Test, measured at initial assessment, 2 day post-intervention follow-up, 1 month follow-up and 3 month follow-up.

Secondary outcome measures

1. Electrophysiological measures of corticospinal excitability, intracortical interactions and interhemispheric balance, measured at initial assessment, 2 day post-intervention follow-up, 1 month follow-up and 3 month follow-up
2. Functional Magnetic Resonance Imaging: Measurement of motor and sensory related brain activation only performed at initial and two day post intervention follow-up

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. History of a single ischaemic stroke, initially affecting the hand
2. Minimum interval since stroke onset one year (no upper limit)
3. Residual impairments of hand function (strength and/or dexterity)
4. Some degree of hand movement defined as present wrist extension (>=20%) and ability to grasp
5. Capable of giving informed consent
6. Aged 18 - 80 years, either sex

Participant type


Age group




Target number of participants

Planned Sample Size: 45

Participant exclusion criteria

1. Intracerebral hemorrhage
2. Large ischaemic lesions involving almost the whole MCA territory
3. Significant tone problems in the hand (greater than 2 in the Ashworth Scale)
4. Severe cognitive impairment defined as mini-mental state examination (MMSE) less than 20
5. Residual aphasia or visual field defect (greater than or equal to 2 in the relative item of the National Institutes of Health Stroke Scale [NIHSS])
6. Past or current history of other neurological or psychiatric disease including epilepsy, previous or recurrent stroke and peripheral neuropathy
7. Major systemic illness
8. Use of anticonvulsant, psychotropic or sedative or medication
9. Excessive use of alcohol or other substances
10. Accepted contraindications for TMS (presence of metal in the head (excluding the mouth), intracardiac lines, cardiac pacemakers)

Recruitment start date


Recruitment end date



Countries of recruitment

Italy, United Kingdom

Trial participating centre

Institute of Neurology
United Kingdom

Sponsor information


University College London Hospitals NHS Foundation Trust (UK)

Sponsor details

Joint UCLH/UCL Biomedical Research Unit
1st Floor Maple House
149 Tottenham Court Road
United Kingdom

Sponsor type




Funder type

Research council

Funder name

Medical Research Council (MRC) (UK) (ref: G0401353)

Alternative name(s)


Funding Body Type

government organisation

Funding Body Subtype

National government


United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2012 results in

Publication citations

  1. Results

    Talelli P, Wallace A, Dileone M, Hoad D, Cheeran B, Oliver R, VandenBos M, Hammerbeck U, Barratt K, Gillini C, Musumeci G, Boudrias MH, Cloud GC, Ball J, Marsden JF, Ward NS, Di Lazzaro V, Greenwood RG, Rothwell JC, Theta burst stimulation in the rehabilitation of the upper limb: a semirandomized, placebo-controlled trial in chronic stroke patients., Neurorehabil Neural Repair, 2012, 26, 8, 976-987, doi: 10.1177/1545968312437940.

Additional files

Editorial Notes