Lower limb rehabilitation using modified constraint-induced movement therapy and motor relearning program on balance and gait in sub-acute hemiplegic stroke: a comparative study

Aims and objectives

Trial design

A single-centre, two arm, parallel group, comparative open labelled superiority trial will be conducted.

Protocol

The model consent form, data collection form and schedule of enrolment, interventions and assessments can be found as Extended data.²⁴ This protocol adheres to the SPIRIT guidelines.²⁵

After gaining clearance from the Institutional Ethics Committee (IEC) of Datta Meghe Institute of Higher Education and Research (Deemed to be University), participants will be enrolled from the Physiotherapy Outpatient Department of Acharya Vinoba Bhave Rural Hospital Sawangi, Meghe, Wardha, Maharashtra. A total of 34 participants will be made aware of the study’s objectives and procedures and will be asked to sign written patient consent forms. All hemiplegic stroke patients who meet the inclusion and exclusion parameter will be included in the study. They will be further separated into Group A and Group B by means of simple random selection. Each group will consist of 17 people in total. The randomization procedure will be conducted using a computer-generated random number system. For sample distribution, we will use the sequentially numbered opaque sealed envelope technique. There will be no blinding procedure in this study. The principal investigator will generate allocation, enrol participants and assign participants to interventions. A departmental committee made up of the Post Graduate (PG), Guide, the Head of Department (HOD), the Principal of the Ravi Nair Physiotherapy College (RNPC) and a member of the Research Guidance Cell will oversee the project. Through routine treatment sessions, we will make sure that the patients follow the suggested treatment plan closely. If necessary, individuals will receive counselling or telephone reminders about their therapy appointments. Prior to and following the analysis, the outcome measures will be assessed. The study’s outcome indicators are as follows: The BBS, DGI, Trunk Impairment Scale (TIS), Functional Reach Test (FRT), 10 Meter Walk Test (10MWT) and Fall Efficacy Scale (FES) along with conventional treatment for balance and gait. mCIMT will be given in Group A in addition to conventional therapy, whereas Group B will receive the MRP in addition to conventional therapy. Figure 1 and Figure 2 depict the study design.

Figure 1. Summary of study process.

Figure 2. Schedule of enrolment, interventions and assessments.

Inclusion criteria

Patients will be included if they fulfil the following inclusion criteria: i) Sub-acute stroke in both men and women between the ages of 45 and 65 years; ii) Mini-Mental State Examination score ≥24; iii) Modified Rankin Scale ≤3; iv) patients with Brunnstrom stage for hand and leg ≥4; v) Modified Ashworth Scale ≤2; and vi) be able to comprehend and adhere to instructions.

Exclusion criteria

The exclusion criteria will be as follows: i) Individuals who are experiencing balance problems as a result of neurological conditions other than stroke (for instance cerebellar impairment, inner ear dysfunction, or Parkinson’s disease); ii) individuals suffering from unstable angina, symptomatic heart failure, or uncontrolled hypertension; iii) acute stroke (flaccid stage); iv) physician determined unstable cardiovascular conditions; v) the patient has been diagnosed as having organ failure, including the heart, kidneys, and lungs; and iv) patients with any traumatic musculoskeletal injury to lower limbs.

Interventions

Criteria for discontinuing allocated interventions for a given trial participant

If any patients in any of the allocated groups develop any complication (e.g., deep venous thrombosis), their participation will be discontinued in the study. The patients will then receive appropriate care and offered outpatient rehabilitation as needed. Study participants will be retained in the trial (unless they withdraw their consent) to enable follow-up data collection and to prevent missing data.

Adherence and concomitant care

During the first consultation, the importance of following the study guidelines and adhering to the allocated group will be highlighted. Exercise adherence will be recorded as a percentage of completed exercises during the first follow up (after the six-week intervention) for both groups. Exercise adherence will be taken into consideration when performing the pre-protocol analysis.

All enrolled patients will be encouraged to contact the principal investigator directly if experiencing problems related to their allocated group intervention. The principal investigator will then fill out a standardized form at these calls. Patients can use medicines and nutritional products as needed, prescribed by their physician. To avoid study-contamination, patients will be asked to adhere to the allocated rehabilitation intervention and not to seek alternative health-care services during the course of the study. Patients will be advised to contact their general practitioner or the principal investigator as needed.

The physiotherapy intervention will be given to Groups A and B for six weeks. The intervention will be provided for 60 minutes, five days each week. Both Group A and Group B will receive conventional treatment. Group A will receive mCIMT along with the conventional therapy, while Group B will receive the motor relearning program along with the conventional therapy. Treatment will be provided to both groups for six weeks.

Modified constraint-induced movement therapy (mCIMT)

Exercises will be given to participants that have a functional focus and will be under supervision. The affected lower extremity will be the focus of these exercises. Based on the desired movements, the therapist (principal investigator) recommended these exercises.

The 30-minute mCIMT approach will consist of the following movements: Transfer package (10 minutes per session), side stepping, ball kicking, stair climbing, and knee control on a step.

Motor Relearning program (MRP)

Participants receive task-specific guidance based on the MRP. This method will be applied for 30 minutes. The actions will be practiced in both sitting and standing and should target an individual’s particular deficits: supine to side-lying to sitting, looking up at ceiling (ensure that centre of body mass does not move back when head is tilted back), without moving one’s feet, turning to gaze over each other’s shoulders and scanning the surroundings for specific items, reaching motions in multiple directions while moving the head and trunk, scooting in bed, altering the base of support (standing with your feet together, in tandem, with one foot on a step, or on one leg), squatting to pick up an object and cross over stepping.

Conventional therapy

Conventional therapy includes: i) Passive and active assisted range of motion exercises for upper and lower extremities; ii) stretching exercises for flexor synergy component shown in Table 1; iii) strengthening exercises with the help of THERABAND shown in Table 2; iv) balance training including practicing reaching beyond arm’s length while sitting and standing; and v) walking training that includes challenge to dynamic balance (e.g., obstacle courses).

Outcome measures

Time frames at baseline and six weeks later.

Primary outcomes

Secondary outcomes

Sample size calculation

We estimated the sample size using a power analysis with 80% power and 5% Type 1 error for the main variables. The BBS score, in comparison to the difference in mean score pre and post treatment for mCIMT group from baseline to end visits. For the study, we used the previously determined effect size difference in percentage from the RCT.²² Formula using mean difference:

Mean ± SD (Pre) result on BBS for mCIMT = 48.8 ± 4.7

Mean ± SD (Post) result on BBS for mCIMT = 52.5 ± 3.5

Difference = 3.7

Pooled std. dev. = (4.7 + 3.5)/2 = 4.1

Considering 10% dropout = 2

Total samples required = 15 + 2 = 17 per group.

Total sample size required = 15

Notations:

$\mathrm{\alpha }=\text{Type I error at 5\%}$

${\mathrm{Z}}_{\mathrm{\beta }}=0.84\left(1-\mathrm{\beta }\right)=\text{Power at}80\%$

$\sigma =\mathit{std}.\mathit{dev}=0.5\text{pooled}\mathrm{std}.\mathrm{dev}$

Data collection methods

Before group allocation, screening of the participants as per the inclusion and exclusion criteria will be carried out. This will be followed by baseline assessment of the outcome measures as mentioned. All participants will undergo the randomization process and are allocated into either group A or Group B. The intervention will be administered for an hour daily, five days per week for six weeks. The post intervention data for the outcomes will be recorded after the last intervention session day. The data will be compiled and analysed for studying the results. The study interventions will be administered by the principal investigator under the supervision of the guide throughout the duration of the study. The patients will be instructed and reminded of the sessions in advance through messages sent to their mobile phones so that adherence to the study is ensured. Furthermore, if the patient misses their sessions due to any reason, the standby days from the week will be utilized such that the patient receives a total of 30 sessions of intervention in the six week duration.

As per in the sample size calculation we have given a 10% dropout rate so that it does not interfere with the results of our study.

The data collection forms can be found as Extended data.²⁴

Data management

The evaluation data will be derived from a pre-set spreadsheet with varied baseline attributes. The research data will be stored in a safe database. Hard copies of evaluation forms, signed informed consent forms, and other non-electronic documents will be safely preserved in the study setting. Every month until the trial is over, a complete backup of the data entries will be performed. The lead investigators will supervise the data gathering and reporting processes. The accuracy of the research papers must be properly reviewed. At the end of the study, the Excel spreadsheet will be published and delivered to the statistician for the necessary analysis. A checklist can be used to avoid data loss due to ineffective staff processes. Due to the thorough follow-up assessment of this trial, participant retention and completion of follow-up assessments are anticipated to be quite high. The patients in this trial will be invited to follow-up exams after six weeks.

Statistical analysis

Samples taken in accordance with the protocol and recorded on a basis that includes all relevant characteristics. Dataset of outcome variables including demographic, physical, laboratory and vitals information will be collected and tabulated in Excel, and will be analysed using R-Software version 4.3. Demographic variables such as age and gender and physical examination (height, weight, BMI), laboratory parameters (haemoglobin, Erythrocyte Sedimentation Rate (ESR), Liver Function Test (LFT), Kidney Function Test (KFT)), and vitals (respiratory rate, pulse rate, systolic blood pressure, diastolic blood pressure and SpO₂ levels) will be collected. Outcome variables such as BBS, DGI, TIS, 10MWT, FRT and FES will be presented over descriptive statistics with categorical tabulation for frequency and percentage, while quantitative measurements with minimum, maximum, mean and standard deviation.

The primary outcome variables will include the BBS for measuring balance and the DGI for measuring gait outcome variables, the secondary outcome variables include the TIS, FRT, 10MWT and FES. Variables as primary and secondary parameters for their measuring assessment at different time visits will be assessed to find the significance in mean at 5% level of significance at P-value < 0.05. Statistical analysis will be performed for hypothesis testing for paired pre and post analysis using a paired t-test for normal data or non-parametric test such as Wilcoxon signed-rank test for non-normal data. Similarly, an unpaired t-test will be used for two independent groups for the change in parameters readings of primary and secondary variables at two different visits.

Data over the outcome variables will be analysed for normality (normal distribution) using Kolmogorov–Smirnov test. If data results over non normal distribution then alternate non parametric test will be used.

Confounding variables will be analysed with generalised linear model to find the random and fixed effects over the outcome variables. Association analysis for finding significance of cofounding parameters will be examined by using Chi-squared test or Fisher’s exact test or by using multi-variant analysis.

Full analysis set for the values of outcome variables will be analysed for the results missing data will be covered with imputation method by calculating the mean and median over the existing data.

Monitoring

Data monitoring

We will have a data monitoring committee lead by the PI for maintaining and integrating of the data.

Harms

The whole procedure is going to held under the supervision of clinicians and departmental committee During the trial, harms and adverse event will be immediately reported to the committee. The final dataset will be uploaded to the institutional research website and will be accessible to concerned authorities.

Auditing

Every month, auditing of the trial is going to be conducted. Any deviation from the protocol will be documented and will be addressed.

Ethical considerations

Datta Meghe Institute of Higher Education and Research, Sawangi Wardha granted ethical approval (date, 21/03/2023) (reference number, DMIHER (DU)/IEC/2023/813). This protocol has been registered on CTRI (trial registration number, CTRI/2023/05/052674; registration date, 16/05/2023).

Protocol amendments

The study has been approved by the Scrutiny Committee at the college level on 01/03/2023 and by the IEC at the university level on 21/03/2023 following which, CTRI registration was also done. As per the suggestions through these committees the study has already been modified and approved. So further changes could not be carried out.

Consent

Members of the trial committee will provide the consent form to the participants in the trial and will inform and explain all the potential benefits and risks to the participants.

Confidentiality

The study program will be elaborated to the participant and one of their relatives, and the principal investigator will take personal information as a part of procedure. The consent form will include the confidentiality statement and signatures of the principal investigator, patient and two witnesses. Whenever it’s necessary to divulge details for the study, consent will be obtained from the patient with complete assurance of their confidentiality.

Access to data

The Principal Investigator will have access to the final trial datasheet.

Ancillary and post-trial care

The whole procedure is going to held under the supervision of clinicians and the departmental committee i.e., Guide, Head of department, Principal and member of Research Guidance Cell.

After the trial session, the participations are going to be under supervision for about four weeks so that if there will be any harm, the Principal Investigator will take care of the participants.

Dissemination policy

We will present the work in International Conference Proceedings and publish in an indexed journal.

Study status

The study is yet to begin.