Combined Transcranial Direct Current Stimulation and Motor Imagery-based Robotic Arm Training for Stroke Rehabilitation

February 11, 2016 updated by: National University Hospital, Singapore

Combined Transcranial Direct Current Stimulation and Motor Imagery-based Robotic Arm Training for Stroke Rehabilitation - a Feasibility Study

Stroke is the most common cause of adult disability. Current treatments for functional loss of the upper extremity post-stroke remain limited in efficacy, particularly for those with moderate to severe impairment.

Previous studies have demonstrated the efficacy of transcranial direct current stimulation (tDCS) for motor recovery post-stroke, a technique of neuromodulation. Motor imagery is effective to enhance motor recovery, with activation of neural pathways similar to that of motor execution. This treatment is accessible to more severely impaired stroke survivors. Our previous studies have demonstrated feasibility and efficacy of motor imagery-based brain computer interface (MI-BCI) for post-stroke motor impairment, in which motor imagery is detected by surface EEG and translated to execution of the target movement with the aid of an arm robot (MIT-Manus).

In this study, we investigate the feasibility of combining robot-assisted MI-BCI training, with tDCS to facilitate post-stroke motor recovery in moderate to severe impairment of upper extremity function. We hypothesise that both tDCS-BCI and sham-BCI will improve motor function in the stroke-affected arm; but that tDCS-BCI will be more effective than sham-BCI. Our secondary aim is to gain insight into the neurophysiological mechanism by comparing the cortical excitability changes following sham-BCI vs tDCS-BCI, using transcranial magnetic stimulation (TMS).

We will conduct a randomized, double-blinded study with MI-BCI combined with tDCS (tDCS-BCI) vs MI-BCI combined with sham-tDCS (sham tDCS-BCI). Subjects will undergo 10 sessions of tDCS each lasting 20 minutes, followed by 40 minutes of robot-assisted MI-BCI training at each session. Primary outcome will be functional ability measured by upper extremity component of the Fugl-Meyer Assessment. Secondary outcome measures will be the Box & Block Test, Modified Ashworth Score (measuring spasticity), grip strength and measures of brain activity including transcranial magnetic stimulation (TMS) measures of magnetic resonance imaging (MRI) measures including functional MRI and diffusion tensor imaging (DTI).

This study will be important to develop a new and effective treatment (tDCS-BCI) for post-stroke motor impairment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a randomised controlled trial of 32 subjects who have sustained their first ever subcortical stroke more than 9 months prior to study enrollment, with upper extremity impairment of 11-45 out of a maximum score of 66 on the Fugl-Meyer assessment scale.

Subjects will be randomly allocated to one of the following 2 groups by using a computer-generated random sequence:

  1. 10 sessions over 2 weeks of MI-BCI training with 20 minutes of tDCS preceding training.
  2. 10 sessions over 2 weeks of MI-BCI training with 20 minutes of sham-tDCS preceding training.

tDCS-BCI protocol Each of the 10 sessions of tDCS-BCI or sham-BCI will be conducted as follows: tDCS will be performed for 20 minutes immediately prior to each session of motor training. The anode will be placed over the M1 motor cortex of the affected hemisphere while the cathode will be placed over the unaffected M1.

After initial calibration, MI-BCI training will involve MI of reaching tasks using the clock game interface of the MIT-Manus robotic system to perform multi-directional reaching movements. Upon detection of the intention to move towards the target on BCI, the robotic arm will complete the reaching movement towards the target. Each training session will last for 40 minutes excluding set-up time and will be undertaken by a research assistant blinded to the condition of tDCS.

Outcome measures Improvement in motor functional ability will be the main outcome of this study. Outcome measures will be assessed at the following time points: prior to treatment initiation, at week 2 (immediate post-training period) and week 6 (4 weeks after completion of training). A clinician blinded to the treatment condition will assess the effects of the intervention. Our primary outcome measure will be the upper extremity score of the Fugl-Meyer Assessment (FMA). This instrument measures upper extremity motor impairment including balance, coordination and speed. Secondary outcome measures for motor function will include (1) Box and Block Test: a timed test in which subjects are required to transfer 1-inch wooden blocks from one side of the box to another. It measures upper extremity manual dexterity and gross motor coordination. (2) Modified Ashworth Scale: is a 6-point measure of spasticity. We will assess the severity of spasticity at the shoulder, elbow, wrist and fingers. (3) Grip strength: will be measured using a hand-held dynamometer.In addition, we will monitor for adverse effects with a questionnaire documenting pain and discomfort at stimulation site, mood changes (using the Beck Depression Inventory), fatigue (using the Fatigue Severity Scale), and cognitive change (using the forward and backward digit span).Assessment of cortical excitability ? single and paired pulse TMS Another aim of this study is to investigate the mechanisms of this combined treatment on cortical plasticity as indexed by cortical excitability changes - assessed by single and paired pulse TMS. We will investigate the resting motor threshold, measured according to the technique of Rossini et al., 1994, before and after treatment, according to the schedule of outcome measures above; paired-pulse stimulation, measuring changes in intracortical facilitation and inhibition.

MRI protocol Patients will be scanned at -2, 0 and 4 weeks to investigate short-term and medium-term changes in fMRI and DTI parameters following tDCS/BCI and sham/BCI treatment. A T1-weighted high-resolution scan and a set of axial fluid-attenuated inversion recovery images will be acquired. T1-weighted and fluid-attenuated inversion recovery images will be realigned and spatially normalized into images of isotropic voxel size implemented in Matlab.The data analysis will include image registration, estimation of diffusion tensor parameters including Apparent Diffusion Coefficient, Fractional Anisotropy, axial and radial diffusivities and tractography using Camino. Reversed phase encoding EPI distortion correction, and regression analysis of DTI, TMS and clinical findings will be performed using Matlab.For fMRI, images will be obtained during the resting state, active/passive hand movement and during imagined arm movement. For the imagined arm movement, subjects will be asked to watch a video on a screen to guide their performance of the imagined movement.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 2

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

  • Singapore
      • Singapore, Singapore, 119074
        • National University Hospital

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

21 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • first ever haemorrhagic or ischaemic subcortical stroke more than 9 months prior to study enrollment
  • upper extremity impairment of 11-45 on the Fugl-Meyer assessment scale

Exclusion Criteria:

  • epilepsy
  • neglect
  • cognitive impairment
  • other neurological or psychiatric diseases
  • severe arm pain
  • spasticity score >2 on the Modified Ashworth Scale in the shoulder or elbow
  • contraindications to TMS or tDCS (cranial implants, ventricular shunts, pacemakers, intrathecal pumps)
  • grip strength <10kg as measured by a dynamometer
  • participation in other interventions or trials targeting stroke motor recovery.

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
Active Comparator: real-tDCS with MI-BCI

10 sessions of the following: 20 minutes of tDCS prior to each session of motor training with the MI-BCI system.

Direct current at an intensity of 1mA with anode placed over the M1 motor cortex of the affected hemisphere and the cathode placed over the unaffected M1.

After initial calibration, MI-BCI training will involve motor imagery of reaching tasks using the clock game interface of the MIT-Manus robotic system to perform multi-directional reaching movements. Upon detection of the intention to move towards the target on BCI, the robotic arm will complete the reaching movement towards the target. Each training session will last for 40 minutes excluding set-up time.
Device: real-tDCS with MI-BCI
As in Arm Description
Sham Comparator: sham-tDCS with MI-BCI

10 sessions of sham tDCS with BCI motor training, each session of which will be conducted as follows:

The same electrode placement and stimulation parameters will be employed for sham tDCS as for real tDCS. However, the current will be applied for 30 seconds only, to give subjects the sensation of the stimulation. This method of sham stimulation has also been validated (Gandiga et al., 2006). Current intensity will be increased and decreased gradually to decrease perception.

MI-BCI training will be the same as the real-tDCS group and will similarly last for 40 minutes.
Device: real-tDCS with MI-BCI
As in Arm Description

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Upper Extremity Component of Fugl-Meyer Assessment
Time Frame: week 0, week 2, week 4
The total FMA score (range, 0-66) on the stroke-impaired upper extremity was used to measure the motor improvements in this study. Higher score indicates better upper limb motor function. FMA were measured at 3 time points: at baseline (wk 0), at completion of intervention (wk 2), and at a 2-week follow-up (wk 4).
week 0, week 2, week 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Resting Motor Threshold of Stroke Affected M1 Motor Cortex
Time Frame: pre- and post-training, 4 weeks post-training

Resting motor threshold (RMT) is defined as the percentage of maximum stimulator output required to elicit motor evoked potential (MEP) with 50 µV peak-to-peak amplitude in at least 4 out of 8 trials during single-pulse transcranial magnetic stimulation (TMS).

Short intra-cortical inhibition (SICI) and intracortical facilitation (ICF) were measured using paired pulse stimulation with an initial conditioning stimulus of 80% of RMT and a test stimulus of 120% of RMT. MEPs were recorded at inter-stimulus intervals (ISIs) of 2, 4, 6, 10 and 15 ms. ISIs of 1-3 ms typically induce SICI while ISIs of 10-15ms typically reflect ICF.

This part of data is still under analyzing.
pre- and post-training, 4 weeks post-training
Grip Strength
Time Frame: pre- and post-training, and again at 4 weeks post-training
Grip strength was measured using a hand-held dynamometer. This part of data is still under analyzing.
pre- and post-training, and again at 4 weeks post-training
Box and Block Test
Time Frame: pre and post training, and 4 weeks post training
Box and block test was to measure the gross manual dexterity. This part of data is still under analyzing.
pre and post training, and 4 weeks post training
MRI Parameters
Time Frame: -2, 0 and 4 weeks
active and passive fMRI, DTI, This part of data is still under analyzing.
-2, 0 and 4 weeks

Collaborators and Investigators

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

Sponsor

National University Hospital, Singapore

Collaborators

National University Health System, Singapore
Agency for Science, Technology and Research

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

January 1, 2011

Primary Completion (Actual)

January 1, 2014

Study Completion (Actual)

January 1, 2014

Study Registration Dates

First Submitted

July 8, 2013

First Submitted That Met QC Criteria

July 8, 2013

First Posted (Estimate)

July 11, 2013

Study Record Updates

Last Update Posted (Estimate)

March 10, 2016

Last Update Submitted That Met QC Criteria

February 11, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIG09may022

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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