Additional identifiers
EudraCT number
ClinicalTrials.gov 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
Acronym
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
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Stroke Research Network; Subtopic: Rehabilitation; Disease: Therapy type
Intervention
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
Other
Phase
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
01/11/2005
Overall trial end date
31/12/2010
Reason abandoned (if study stopped)
Eligibility
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
Patient
Age group
Adult
Gender
Both
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
01/11/2005
Recruitment end date
31/12/2010
Locations
Countries of recruitment
Italy, United Kingdom
Trial participating centre
Institute of Neurology
London
WC1N 3BG
United Kingdom
Sponsor information
Organisation
University College London Hospitals NHS Foundation Trust (UK)
Sponsor details
Joint UCLH/UCL Biomedical Research Unit
1st Floor Maple House
149 Tottenham Court Road
London
W1P 9LL
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Research council
Funder name
Medical Research Council (MRC) (UK) (ref: G0401353)
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
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 http://www.ncbi.nlm.nih.gov/pubmed/22412171
Publication citations
-
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.