A Randomized, Controlled Clinical Trial of Upper Limb Training With Bilateral Cutaneous Electrical Stimulation to Improve Upper Limb Functions in Patients With Chronic Stroke
Phase: NA
Conditions: Stroke
Sponsor: The Hong Kong Polytechnic University

Research Ttile:  
A randomized controlled clinical trial of upper limb 
training with bilateral cutaneous electrical 
stimulation to improve upper limb functions in 
patients with chronic stroke 
 
NCT number:  
NCT03112473 
 
Date of Document:  
2021.3.1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

The Hong Kong Polytechnic University 
Department of Rehabilitation Sciences 
 
Research Project Informed Consent Form 
 
Project entitled: A randomized controlled clinical trial of upper limb training with 
bilateral cutaneous electrical stimulation to improve upper limb functions in patients with 
chronic stroke 
 
Investigator: Dr. Shamay S. M. Ng (RS), Dr. Raymond C.K. Chung 
 
Purpose: 
To investigate whether bilateral cutaneous electrical stimulation over both paretic and 
non-paretic upper limb (bilateral ES) will be more superior to cutaneous electrical 
stimulation over paretic upper limb (unilateral ES) when combined with task-orientated upper 
limb training (TOT) respectively. 
 
Methods: 
All eligible subjects will be randomly assigned into 4 groups: (1) bilateral cutaneous 
electrical stimulation over both paretic and non-paretic upper limb (bilateral ES) and (2) 
unilateral cutaneous electrical stimulation over paretic upper limb (unilateral ES), (3) 
bilateral placebo electrical stimulation over both paretic and non-paretic upper limb 
(placebo ES) combined with task-orientated upper limb training (TOT) respectively for 8 weeks, 
3 times a week (total 20 treatment sessions). (4) No active treatment. Subjects will 

be assessed on improvement of the Wolf Motor Function test, Fugl Meyer Assessment Upper 
Extremity Portion, and Motor Activity Log Questionnaire. 
 
Potential Risks and Benefits: 
The major benefit from participating in this study is that subjects may have the 
opportunity to know their own level of motor functions of their upper limbs. The results may 
also be beneficial for planning an intensive rehabilitation program for improving upper limb 
motor functions in patients with stroke. The electrical stimulation and testing procedures have 
been well proved to be safe and used with negligible side effects, both 
clinically and experimentally. A few subjects may feel some exhaustion during assessment and 
therefore rest will be allowed between assessment procedures. 
 
Informed Consent: 
I,  
, understand the details of this study. I voluntarily consent to 
participate in this study. I understand that I can withdraw from this study at any time without giving 
reasons, and my withdrawal will not lead to any punishment or prejudice against me. I am aware 
of any potential risk in joining this study. I also understand that my personal information will not 
be disclosed to people who are not related to this study and my name will not appear on any 
publications resulted from this study. 
 
I can contact the chief investigator, Dr. Shamay Ng at telephone 2766-4889 for any questions 
about this study. If I have complaints related to the investigators, I can contact Ms. Gloria Man 
secretary of Departmental Research Committee, at 2766-4394. I know I will be given a signed 
copy of this consent form. 
 
Signature (participant):  
Date:   
 
 
Signature (Witness):  
Date:   
 

Methods 
Design 
 
 
This study was a single-blinded randomized, placebo-controlled trial. The study was 
registered on ClinicalTrials.gov (NCT03112473) and conducted in our neurorehabilitation 
laboratory. Informed consents were obtained before the study began. The study protocol was 
approved by the ethics committee of the Hong Kong Polytechnic University and conducted in 
accordance to the Declaration of Helsinki. 
 
 
As there was no previous study investigating the effect of Bi-TENS+TOT in improving 
the upper limb motor control in people with stroke, the effect size (Cohen’s d=0.314) used for 
the calculation of sample size in this study was obtained from our pilot trial. The sample size was 
calculated by using G*power version 3.1.0 (Franz Faul, Universitat Kiet Germany) with α of 
0.05, power of 0.80, correlation among measure of 0.5 and non-sphericity correlation of 1. 
Ninety-six subjects were necessary to detect a significant between-group difference in the 
improvement of the upper limb motor control measured by FMA-UE. In accordance to our 
previous clinical trial, dropout rate of was assumed to be 20%, so a buffer of 24 subjects would 
be included. A sample size of 120 (30 per group) was used to detect the significant between- 
group difference finally. 
The randomization was conducted by a research assistant who did not involve in the 
intervention and assessment after the baseline measurement. The eligible subjects were stratified 
into one of the four groups randomly: Bi-TENS+TOT group, Uni-TENS+TOT group, Placebo- 
TENS+TOT group and Control group. The stratification was conducted by the online software 
“Minimize”. The factors of age (50-60, 60-70,>70), sex (male, female), type of stroke (ischemia, 
hemorrhage) and side of lesion (left, right) were balanced in the four groups. To achieve 
concealment, the allocation information was kept by the research assistant. Following the 
provision of informed consent, subjects were informed of their allocation to one of four groups, 
but specific group allocation remained concealed to maintain the blinding of treatment. 

 
 
Subjects 
 
 
One hundred and twenty subjects (mean age=61.70±5.91 years) were recruited 
from the local self-help groups. The inclusion criteria of the subjects included: (1) were between 
50 and 80 years of age; (2) had been diagnosed with stroke within 1 to 10 years; (3) had 
volitional control of the non-paretic arm and at least minimal antigravity movement in the paretic 
shoulder; (4) had at least 5 degrees in wrist extension in the antigravity position; (5) had an 
Abbreviated Mental Test score >7. The participants were excluded if they: (1) had any additional 
medical, cardiovascular or orthopedic condition; (2) had contraindications to TENS, such as 
implant cardiac pacemaker, skin allergy; (3) had receptive dysphasia; (4) had a significant upper 
limb peripheral neuropathy; (5) were involved in drug studies or other clinical trials; (6) had 
severe shoulder, elbow, wrist or finger contractures. 
 
 
Intervention 
 
TENS protocol 
 
 
With reference to previous studies, the dosage of 20 sessions of 60-minute TENS could 
provide sufficient stimulus to elicit recovery of motor function in people with chronic stroke. In 
the Bi-TENS group, the subjects received TENS on both paretic and non-paretic sides of the 
upper limbs. In the Uni-TENS group, TENS was only applied on the paretic side of the upper 
limb while a placebo stimulation (P-STIM) was applied on the non-paretic side. In the Placebo- 
TENS+TOT group, the P-STIM was applied on both sides of the upper limbs. In the Control 
group, the subjects did not receive any active treatment. The disposable surface electrodes were 
applied to stimulate the median nerve (from the carpal tunnel to flexor digitorum superficialis) 
and superficial radial nerve (from the extensor pollicis longus to extensor digitorum communis). 

The stimulator was 120z Dual-Channel TENS Unit (ITO 
PHYSITHERAPY&REHABILITION CO., LTD, Tokyo, Japan). The parameter (100 Hz, 0.2 ms 
square pulses, intensity barely below the motor threshold) of TENS followed our previous study 
(10). The P-STIM was provided by identical-looking TENS devices that electrical circuit has 
been disconnected. 
 
TOT protocol 
 
The TOT protocol was developed based on the guideline of stroke rehabilitation (40). 
Under the supervision of a well-trained research assistant with health-related discipline training, 
the subjects with stroke were required to complete six 10-minute training items in each session 
of treatment, including stretching exercises, mobilizing exercise, strengthening exercises, seated 
reaching tasks, dexterity training and bimanual practice. Five minutes’ interval for resting was 
provided between each training item. 
 
 
Outcome Measure 
 
To eliminate the bias, an experienced rehabilitation therapist who was blinded to the 
group allocation assessed all outcome measures in a random sequence for 5 times, including 
baseline, mid-intervention (4th week of study), post-intervention (8th week of study), 1-month 
follow-up and 3-month follow-up. 
 
 
Primary Outcome 
 
Fugl-Meyer Assessment of upper extremity (FMA-UE) 
 
 
 
FMA-UE was used for evaluating the upper limb motor control in people with stroke. 
FMA-UE showed an excellent inter-rater (r=0.997) and test-retest (r=0.965) reliability in people 
with chronic stroke. FMA-UE has 4 subsections: (1) shoulder-arm; (2) wrist; (3) hand; (4) 
coordination and speed. There was a total score of 66 with 33 items with ordinal scoring from 0 
to 2. 

 
 
Secondary Outcome 
 
The Peak Torque and co-contraction ratio of Maximum Voluntary Contraction (MVC) 
 
 
 
Peak torque and co-contraction ratio was used to assess the muscle strength and abnormal 
muscle activation. The raw force data and electromyography (EMG) signal was record by the 
custom-built measurement frame mounted with load cell and surface EMG, respectively. At the 
beginning, the subjects were seated with shoulder flexion 0°, elbow flexion 0° and wrist 0° 
neutral position placed in the torque measurement. The paretic hand was fixed by stripe and the 
forearm was fixed by G-clamp. The 2 bar-shaped electrodes were placed on flexor carpi ulnaris 
and extensor carpi ulnaris. During data collection, the subjects were required to perform 5 
seconds isometric MVC of wrist extension/flexion, respectively. Each movement was performed 
3 times. The data of the 3 trials were averaged. 
The torque of the movement was the product of the force and moment arm, which is the 
length from the transverse crease of the wrist to the head of the 3rd metacarpal. The peak torque 
would be recorded by extracting the peak value of torque being produced during MVC. Excellent 
intra-rater reliability ranged from 0.97 to 0.98 were reported in our pilot study. 
 
 
The raw EMG was rectified and filtered by a band pass filter (20-450Hz) and a notch 
filter (49Hz-51Hz) by Butterworth method. Then the EMG signal would be integrated. The time 
window beginning at 0.25 seconds before and end at 0.25 seconds after the peak torque occurred 
was captured to calculate the integrated EMG (iEMG) of the agonist and antagonist. The co- 
contraction ratio would be calculated by the following formula: 
Co-contraction Ratio= 
𝑖𝑖𝑖𝑖 𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖
 
𝑖𝑖𝑖𝑖 𝑖𝑖𝑖𝑖𝑖𝑖𝑖+𝑖𝑖𝑖𝑖 𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖 × 100% 
 
Good to Excellent intra-rater reliability ranged from 0.837 to 0.975 were reported in our 
pilot study. 

ROM of wrist and elbow 
 
 
 
The ROM of wrist and elbow were measured by the electrogoniometer (Model SG 110; 
Biometrics, Gwent, UK). The electrogoniometer showed a high intra-rater (r=0.90-0.92) 
reliability (44) in people with stroke. The subjects performed maximal ROM of wrist 
flexion/extension and elbow flexion/extension with their paretic side twice. The mean values of 2 
trials were recorded. 
 
 
Action Research Arm Test (ARAT) 
 
 
 
ARAT was an objective scale to assess the upper limb motor function. Previous study 
showed that ARAT showed an excellent intra-rater (r=0.996-0.997) and inter-rater (r=0.989) 
reliability in people with chronic stroke. This ordinal scale consists of 19 items with a total score 
of 57. The quality of the performance on each item was rated from 0 to 3. 
 
 
Jacket Test (JT) 
 
 
 
JT was an objective scale to evaluate the upper limb motor function by completion 
time of dressing task, which included shoulder abduction, flexion and elbow extension and hand 
gripping. JT showed a good to excellent intra-rater (r=0.845-0.891), inter-rater (r=1.000-1.000) 
and test-retest (r=0.781-0.795) reliability in people with chronic stroke. The subjects were 
required to put on a jacket or cardigan sweater straight on his or her shoulders, and then took it 
off completely for 3 trials. The completion time of the 3 trials was averaged. 
 
 
Motor Activity Log (MAL) 

The MAL questionnaire was a subjective scale to assess upper limb motor function. 
Subjects were required to rate the amount of use (AOU) and the quality of movement (QOM) of 
their paretic upper limb from 0 to 5 in 30 items of ADL. MAL showed a good reliability in both 
components of AOU (ICC=0.79) and QOM (ICC=0.82) in people with stroke. A higher score of 
AOU and QOM indicated that higher usage frequency and better performance of their paretic 
upper limbs, respectively. 
 
 
Community Integration Measure (CIM) 
 
 
 
The Chinese version of CIM was used to assess the community integration level. CIM 
showed a good test-retest reliability (ICC=0.84) in measuring the people with chronic stroke. 
CIM consists of 10 items, each item rated from 1 to 5, giving a score ranged from 10 to 50. A 
higher score indicated a higher level of community integration. 
 
 
 
 
Statistical Analysis 
 
 
 
 
 
All the quantitative analyses were performed by the SPSS (Version 23.0, IBM, Armonk, 
NY). Descriptive analysis was used to summarize subjects’ demographic information. One-way 
analysis of variance, Chi-Squared test (χ2 test) and Kruskal-Wallis test were used to compare the 
baseline characteristics of the four groups as appropriate. Intention-to-treat analysis (last 
observation carry forward) was used. The linear mixed models (LMM) were used to compare the 
changes over time in variables of interest between those in the Bi-TENS+TOT group and those 
in the Uni-TENS+TOT group, Placebo-TENS+TOT group and Control group. The maximum 
likelihood estimation was used to selected the best fit model. The first-order autoregressive 
structure with heterogeneous variances (AR (1): heterogeneous) was used to estimate the 

parameters of statistical model. The intervention effect from pre-intervention to post-intervention 
was analyzed by LMM. The carryover effect from post-intervention to 3-month follow-up 
assessment was analyzed using the same LMM method. The significant level was set at 0.05. 
The post-hoc analysis would be conducted by Bonferroni correction when there was an overall 
significant difference.