Optimizing Motor Functions in Incomplete Spinal Cord Injury with Simultaneous Application of Transcranial Direct Current Stimulation and Virtual Reality Assisted Treadmill Training: A Study Protocol for a Randomized Controlled Trail

Optimizing Motor Functions in Incomplete Spinal Cord Injury with Simultaneous Application of Transcranial Direct Current Stimulation and Virtual Reality Assisted Treadmill Training: A Study Protocol for a Randomized Controlled Trail | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Optimizing Motor Functions in Incomplete Spinal Cord Injury with Simultaneous Application of Transcranial Direct Current Stimulation and Virtual Reality Assisted Treadmill Training: A Study Protocol for a Randomized Controlled Trail Garima Wadhwa, Pooja Anand, Priyanka Rishi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6750457/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Incomplete complete spinal cord injury (iSCI) leads to significant motor impairments, affecting mobility and quality of life. Emerging rehabilitation strategies, including neuromodulation and virtual reality treadmill training, have shown potential in enhancing motor recovery among individuals with neurological conditions. However, the synergistic effects of their simultaneous application remain underexplored. This study protocol outlines a randomized controlled trial (RCT) to investigate the synergistic effects of transcranial direct current stimulation (tDCS) and virtual reality-assisted treadmill training (VRATT) on motor functions in individuals with iSCI. Methodology This study is a single-blind, two-group randomized controlled trial. 52 individuals with incomplete spinal cord injury will be recruited based on inclusion criteria. They will be randomly allocated to transcranial direct current stimulation (active or sham group). Both the groups will simultaneously receive virtual reality-assisted treadmill training. The intervention will be provided for 15 sessions over a span of four weeks. Outcome measure Lower extremity motor score will be used for assessment of muscle strength of lower extremities; balance assessment will be done through Berg balance scale and functional reach test. Kinetic and kinematic parameters of the gait cycle will be analyzed with the Walker View treadmill. Walking ability and walking speed will be determined using the Walking Index for Spinal Cord Injury (version II) and the 10-meter walk test, respectively. Discussion The trial will provide new knowledge about the effectiveness of combined transcranial direct current stimulation with VR-assisted treadmill training on motor functions, functional independence, and quality of life of individuals with SCI. Trail Registration Clinical Trials Registry – India, CTRI/2024/11/076226, Registered on 04/11/2024 spinal cord injury neuromodulation gait rehabilitation Treadmill training innovative strategies Figures Figure 1 Background Spinal cord injury (SCI) is a devastating form of disability causing temporary or permanent loss of motor, sensory, or autonomic functions below the level of injury [ 1 , 2 ]. Individuals with spinal cord injuries tend to develop severe complications in the physical, psychological, and social domains. The physical impairments may range from spinal or musculoskeletal deformities due to disturbances in muscle balance, spasticity, or the development of contractures. The psychosocial issues involving fatigue, tiredness, mood disorders, or depression are also commonly encountered in this population [ 1 – 7 ]. Moreover, the disruption of communication between the brain and the lower extremities impedes the initiation and execution of purposeful movements that are required for balance, ambulation, and functional activities [ 8 – 10 ]. The coordination and integration of visual, vestibular, and proprioceptive feedback, as well as reflexive limb control, results in a balanced body [ 11 ]. Impairments in muscle strength, muscle tone, and sensory systems lead to a loss of balance [ 12 , 13 ]. Poor balance is a major cause of falls among individuals with spinal cord injuries [ 14 ]. Falls can result in injuries such as fractures, bruises, and ulcers, which may further complicate the rehabilitation process. Beyond physical injury, the fear of falling can lead to reduced activity participation, social withdrawal, and decreased confidence in performing daily tasks. Additionally, individuals with SCI tend to develop slow, inefficient, unbalanced, or uncoordinated gait patterns. They usually walk slowly, with a long cycle time and little strides [ 15 ]. Lemay et al. (2015) showed that the most critical and challenging situations for patients with incomplete SCI are the initiation and termination of gait. More specifically, gait initiation and termination occur at slower speeds, and in comparison, termination of gait is more challenging than initiation of gait [ 16 ]. Regaining walking abilities has been considered the topmost priority and a major challenge of rehabilitation for individuals with spinal cord injury. Various approaches, including virtual reality [ 17 ], partial body weight support treadmill training [ 18 ], overground training, and robotic training, have shown promising results in improving the balance and gait of individuals with spinal cord injury [ 19 ]. However, no one approach has been found to be superior to the other. The growing body of research is emphasizing the role of neuromodulation, including transcranial direct current stimulation alone or in adjunct with other therapies. Recent evidence has explored the beneficial effects of transcranial stimulation on locomotor functions and upper extremity functions among individuals with neurological disorders [ 20 – 24 ]. The application of transcranial direct current stimulation among individuals with spinal cord injury has been tested for improving motor functions and locomotion and for reducing neuropathic pain [ 25 – 28 ]. However, the available evidence has shown mixed results for individuals with SCI. The recent study by Klaumren (2024) noted significant improvement of tDCS on the walking speed of individuals with SCI when it was applied in conjunction with overground walking [ 25 ]. In contrast, the study by Evans [ 27 ] and Nijhawan [ 28 ] did not find any addictive effect of tDCS on walking speed and quality of life, respectively, of individuals with spinal cord injury. Another innovative approach that has been hypothesized to enhance neuroplasticity is the combination of virtual reality along with treadmill training (VR-TT). The virtual reality system enhances the engagement of individuals by providing an interactive environment, while the treadmill offers a high-intensity, controlled, and repetitive movement pattern. The use of VR-TT in gait and balance training has demonstrated improvements in motor control and functional mobility in individuals with neurological impairments, including stroke, cerebral palsy, and multiple sclerosis [ 29 – 31 ]. Given the individual benefits of tDCS and VRTT in promoting motor function recovery, their simultaneous application holds the potential to achieve synergistic effects and functional outcomes in incomplete spinal cord injury (iSCI) rehabilitation. Considering the utmost importance of regaining balance and ambulatory function in iSCI, this study aims to evaluate the efficacy of the simultaneous application of tDCS and VRTT in optimizing motor function recovery in individuals with iSCI. This may provide a new, evidence-supported approach to improving balance and gait outcomes and overall functional independence of individuals with iSCI. Methods The aim of the proposed study is to evaluate the synergistic effect of transcranial direct current stimulation and virtual reality-assisted treadmill training on the motor functions and quality of life of individuals with incomplete spinal cord injury. Study Design A prospective, single-blind, parallel two-group randomized controlled design with equal allocation (1:1) will be undertaken. Setting of the study A convenient sample of 52 participants with incomplete spinal cord injury will be recruited from the in-patient and out-patient physical medicine and rehabilitation (PMR) department of the Indian Spinal Injuries Center, New Delhi, India Participants All participants will be provided with the information sheets, and written consent will be obtained by the principal investigator before recruitment. The participants will be selected based on the eligibility criteria mentioned in Table 1 . Medical clearance will be taken for all participants before enrollment into the intervention. This research protocol is consistent with the current Consolidated Standards of Reporting Trials (CONSORT) guidelines (Fig. 1) and is developed in accordance with the Standard Protocol Items: Recommendations for Interventional Trails (SPIRIT Schedule) [ 32 ] (Table 2 ) and the SPIRIT checklist are attached in additional file 1. A visual description of the study regarding enrollment, assessment, and intervention is depicted in Table 2 . Baseline assessment (T0) will be done before allocation, and post-intervention assessment (T1) will be taken after 15 intervention sessions, which will serve to compare the short-term effect of the respective intervention. The DRC and IEC Committees of (… name is not mentioned here for the purpose of blind review; it will be added later) maintain track of all potential recruiters and monitor data collection during the intervention. The members of the DRC, along with the consultants and physiotherapists in the hospital, provide day-to-day support to all aspects of the local organization of the trial. The guides and co-guides are in charge of the trial and supervise the trial frequently. Table 1 – Eligibility Criteria Eligibility Criteria Inclusion Criteria Traumatic or non-traumatic incomplete spinal cord injury. Categorized as American Spinal Injury-Association Impairment Scale Grade C and D. Level of injury from T1 to L2 . Age between 18–65 years. At least 3 months after SCI. Functional ambulatory category - ≥ 3. Individuals with SCI able to advance leg independently with the treadmill speed at 0.2 km per hour. Exclusion Criteria Any other pre-existing neurological problem, musculoskeletal condition, cardiovascular or psychiatric problem which may interfere with the treatment. Spasticity of grade 3 or more in lower extremities on Modified Ashworth Scale which may interfere with the treatment. Visual or auditory impairment such that it impacts on the ability to participate. Body Weight more than 150 kg. Skin lesions or rash at potential sites which may interfere with the treatment or placing of electrodes of transcranial direct current stimulation or Grade 2 or higher-pressure ulcers (according to the National Pressure Ulcer Advisory Panel classification) that interfered with harness support or walking or standing. History of seizure, migraine, headache or epilepsy, brain surgery. History of recent episode of orthostatic hypotension or autonomic dysreflexia. Cardiac pace-maker. Pregnancy. Intracranial or skull implants. Previous experience of transcranial direct current stimulation or VR assisted treadmill training post SCI. Table 2 Schedule of enrollment, interventions and assessments according to the Standard Protocol Items: Recommendations for Interventional Trials Guideline Variables Enrollment Allocation Baseline (T0) Intervention Post- Intervention assessment (T1) Enrollment - Eligibility Screen x - Informed Consent x - Medical Clearance x - Allocation x Interventions x - Active tDCS + VR-TT group x - Sham tDCS + VR-TT group Assessments - Functional Ambulatory Category x - Walking index for spinal cord injury x x x - Lower Extremity Motor Score x x x - Technobody Walker view Gait assessment • Step length (RT and LT side) • ROM of Hip joint (RT and LT side) • ROM of knee joint (RT and LT side) • Average Range of trunk flexion- extension • Average range of trunk Lateral flexion • Vertical Displacement of COG x x x - Berg Balance Scale x x x - Functional Reach Test x x x - 10- meter Walk test x x x - SCIM x x x - WHO-QOL BREF x x x Active tDCS + VR-TT group, Active transcranial direct current stimulation and virtual reality treadmill training group; Sham tDCS + VR-TT group, Shan transcranial direct current stimulation and virtual reality assisted treadmill training group; RT, Right side; LT, Left side; ROM, range of motion of joint; COG, center of gravity, SCIM, Spinal cord Independence Measure, WHO-QOL BREF, World Health Organization- Quality of life -BREF scale. Ethical Consideration The study received approval from the ethical committee of the organization (the name is not mentioned here for the purpose of blind review; it will be added later) under the protocol number (ISIC/RP/2024/032) and is registered with the Clinical Trials Registry (number will be added later, kept anonyms for blind review). The participants will be informed orally and in writing about the purpose of this trial, benefits of participation, potential risk, and rights to withdraw from the trial at any point during the study before the screening. The data of the participants will be collected, documented, and managed confidentially. The authors related to the trial will have access to the final trial dataset. Termination Criteria The intervention will be terminated immediately if any signs or symptoms of autonomic dysreflexia are observed in participants or if any kind of uneasiness is reported by the participants. Sample Size A priori sample size estimation was done using the statistical formula mentioned below by considering the Waking Index for Spinal Cord Injury (WISCI II) scale as the primary outcome measure. The data used for calculation was based on the study carried out by Simis et al. [ 33 ]. The alpha value was kept at 0.05 at 80% power and with a 10% dropout rate. The total calculated sample size comes out to be 52 (26 in each group). Formula used for sample size calculation: $$\:\text{n}=\frac{({{\sigma\:}}_{1}^{2}+{{\sigma\:}}_{2}^{2}){{(\text{Z}}_{1-\propto\:/2}\:+{\text{Z}}_{1-{\beta\:}})}^{2}}{{\text{d}}^{2}}$$ Randomization Eligible candidates will be assigned randomly to either the active anodal intervention group (active transcranial direct current stimulation along with virtual reality-assisted treadmill training) or the sham interventional group (sham transcranial direct current stimulation and virtual reality-assisted treadmill training) with a 1:1 allocation. Randomization will be performed using a computer-generated randomization sequence defined by random allocation software 2.0. Randomization and group allocation will be carried out by a blinded investigator. Allocation Concealment The allocation schedule will be sequentially marked as Group A—active transcranial direct current stimulation with virtual reality-assisted treadmill training and as Group B—sham transcranial direct current stimulation with virtual reality-assisted treadmill training and will be sealed in opaque envelopes to ensure concealment. Furthermore, an individual not associated with this study will sequentially open the concealed envelopes to reveal the participants' group allocation. The principal investigator will be informed of the group allocation given the nature of the intervention. Blinding The trial is a single blinded study where the participant will be blinded to group allocation. Also, the statistician who will analyze the data would be unaware of the identification of treatment groups. Description of the Devices – Transcranial direct current stimulator—Caputron Brain Premier tDCS Device E1 will be used. It is an anodal and cathodal monophasic current device. Wet-type sponge surface electrodes (1.5 inches in diameter) soaked in saline will be employed. Rubber straps will be used to securely place the electrodes on the skin surface. Virtual Reality Assisted Treadmill Trainer—For virtual reality-assisted treadmill training and for gait assessment, “Walker View TM, Techno Body” will be used. The treadmill is equipped with a sensorized belt with 8 load cells that detect the patient load, a motion capture 3D camera, a speed control system, and a 49” wide LCD screen (liquid crystal display screen). It provides complete gait analysis through a 3D camera and load cells. The walking speed can be set in the range of 0–20 km/hr, with incremental speed of 0.2 km/hr. The system has integrated software—the Technobody management system. Intervention and Duration Transcranial direct current stimulation—The anodal electrode will be placed over the primary motor cortex M1 region according to the international 10–20 electroencephalogram standardized system. The cathodal electrode will be placed over the supraorbital region contralateral to the anodal electrode. A constant 2 mA direct current will be delivered in the anodal group with a gradual current ramp-up and ramp-down of 30 seconds. The intensity and duration were selected based on the previous studies demonstrating these parameters to be safe [ 25 , 28 , 33 ]. The electrode placement for the sham group will be similar. However, the participant will only receive current for the initial 30 seconds, and then the power will be turned off for the remaining period. VR-Assisted treadmill training—Participants need to walk on the walker view treadmill with the initial speed of 0.2 km/hr while viewing a virtual screen placed in front of the treadmill. The participant needs to walk for 20 minutes in each session. The intervention will be the same for Group A and Group B. The virtual screen progression is divided into three phases. Individuals in either group will receive 15 sessions over a span of three weeks. Individuals will also receive individualized conventional physiotherapy sessions. The details of the intervention are described in Table 3 . Table 3 Details of the intervention in each group Intervention Details of Intervention Transcranial direct current stimulation (1 to 15 sessions) - Active tDCS + VR- TT Group Location - Anode- Primary motor area- M1 Cathode- supra-orbital area Intensity − 2MA, (Initial 30 seconds- ramp up, last 30 seconds- ramp down) Duration- 20 Minutes (10 minutes each hemisphere) - Sham tDCS + VR-TT Group Location - Anode- Primary motor area- M1 Cathode- supra-orbital area Intensity – Initial 30 seconds Ramp up to 2 MA, then switched off Duration- 20 Minutes (10 minutes each hemisphere) Virtual Reality Assisted Treadmill Training – Same for both groups Description Participants need to walk over the treadmill with initial speed of 0.2 kn/ hr. The virtual screen Infront of the treadmill will be progressed in three phases mentioned below Progression of the virtual screen Phase 1 (1-– 5 sessions)- Visual feedback mode with sensor activation and Foot steps tiles Phase 2 (6–10 sessions)Virtual reality slow moving VR scenes (that depicts the view of park/ city levels) Phase 3 (11–15 sessions) -Virtual reality video mode with distractions Progression of the treadmill - Starting speed 0.2km/hr increased on individual basis. - If patient is able to maintain correct body alignment at 0.8km/hr speed, 1% inclination will be done. - Participant can take side bars support but encouraged to reduce support. - No overweighing harness done i..e no partial weight upliftment done. However for initial sessions harness was used for fall protection if needed. - AFO’s/ Braces allowed while walking if required Conventional Rehabilitation Physiotherapy Individualized structured physiotherapy sessions consisting of range of motion of joint exercises, strengthening exercises, stretching of spastic muscles, sitting balance training, core training etc Adherence The adherence of the participants to the training protocol will be monitored through documentation of participants’ attendance in sessions. In accordance with the "intention-to-treat" principle, if the participants are unable to complete all of the sessions within the allotted three weeks, they may extend the training period by one week. The nature, scope, and trend of missing data throughout the investigation are also clearly disclosed by the authors. Outcome Measure Assessment and procedure to measure 1) Strength Assessment The lower extremity motor score (LEMS), a subscale of the American Spinal Injury Association (ASIA) classification, will be utilized to measure the strength of the lower extremity key muscles in accordance with the standard neurological assessment developed by ASIA. The strength of the muscle is graded on a 6-point scale ranging from total paralysis (0) to normal active movement with a full range of motion against gravity and full resistance (5). The total LEMS score is calculated by adding the bilateral lower extremity key muscle power with a total possible score of 50. The five key muscles include hip flexors, knee extensors, ankle dorsiflexors, long toe extensors, and ankle plantar flexors of each leg [34]. 2) Balance Assessment Berg Balance Scale: The Berg Balance Scale (BBS) is a clinical measure of balance consisting of 14 tasks of progressing difficulty. Each task is graded on a five-point ordinal scale with 0 indicating the lowest degree of function and 4 indicating the highest level of function. The total number of points that can be earned ranges from 0 to 56. The ability to complete the tasks without help and to meet time or distance requirements determines the score. The BBS has shown to have excellent inter-rater (ICC 0.98) and intra-rater reliability (ICC 0.97) [35, 36]. Functional Reach test: At the height of the subject's acromion process, a leveled yardstick will be affixed to the wall to measure the reaching distance. Participants will be asked to make a fist and extend their arm forward (position 1), and the placement of the end of the third metacarpal along the yardstick will be recorded. Subjects will then need to reach as far forward as they can without losing their balance or taking a step (position 2), and the placement of the end of the third metacarpal will again be recorded. Functional reach distance will be measured as the mean difference between positions 1 and 2 over three trials [37]. 3) Gait Assessment Kinematic and kinetic parameters of gait: The TechnoBody Walker view treadmill system will be employed for assessment of kinetic and kinematic parameters of the participant’s gait cycle. To begin with analysis, the therapist selects gait analysis from the test icon and then selects the neurologic module from the options. The test speed will be kept constant at 0.2km/h and the duration at 2 minutes for every participant and at each test (pre- and post-). The walker view proprietary software calculates spatiotemporal gait parameters and kinematic variables automatically, including average cycle time (cycles/seconds), left and right step length (measured in centimeters), left and right hip range of motion of joint (measured in degrees), left and right knee ROM (measured in degrees), trunk flexion-extension ROM (measured in degrees), trunk lateral flexion ROM (measured in degrees), vertical displacement of Center of Gravity (measured in centimeters), and load symmetry (measured in %), and the treadmill program generates a report for each trial, which will then be used in data analysis. Walking Ability: Walking Index for Spinal Cord Injury II (WISCI -II) will be used for assessment of the walking ability of the participants. It employs an ordinal scale with 21 levels. This scale assesses walking ability based on the need for physical assistance, braces, and walking aids. The individual needs to walk a distance of 10 meters. The maximum level at which walking is safe will be assessed, with 0 indicating no walking and 20 indicating unlimited walking. Furthermore, in the SCI population, it has been demonstrated to have outstanding inter- and intra-rater reliability (1.00) and repeatability (ICC, 0.995) [38]. Walking Speed: 10-Meter A walk test will be administered for walking speed. Participants will be asked to walk with/without an assistive device independently for 10 meters. The observation in the intermediate 6 meters will be recorded. The duration in seconds will be recorded under preferred speed and fast speed scenarios. Three trials will be performed, and the average of the three trials will be used for analysis. The 10-meter walk test has high inter- and intra-rater reliability [39]. 4) Functional Assessment The Spinal Cord Independence Measure—a self-report measure—will be used for functional performance assessment. It consists of 19 items under three domains, i.e., self-care, respiration and sphincter management, and mobility. Scores will be higher for those who are able to complete the activities mentioned with less assistance, aids, or medical compromise. The total scoring of the scale ranges from 0 to 100. The SCIM III has been found to be an excellent measure for functional independence for individuals with spinal cord injury with an interclass correlation of 0.94 and a Cronbach alpha value of 0.70 [40]. 5) Quality of Life The World Health Organization Quality of Life-BREF (WHOQOL BREF) is a 26-item scale covering the four domains, including physical health, psychological health, and social and environmental domains. Participants need to rate the intensity of selected attributes of QOL as per the previous 2 weeks on a 5-point Likert response scale for every item. The mean score will be obtained as per the criteria to compute the mean of the transformed score from each domain. In people with SCI, all WHOQOL-BREF domains have been found to exhibit strong internal consistency (Cronbach α range, 0.74–0.78), with the exception of the social interactions category (α=0.54) [41]. Statistical Analysis The student t-test for numerical variables will be used to check if the randomization process created between groups has participants with homogeneous clinical characteristics before the intervention, thereby avoiding potential selection bias. Characteristics of participants will be descriptively summarized for age, gender, time since injury, level of injury, ambulatory level, etc., using mean, standard deviation, or frequency. The Shapiro-Wilk test will be used to know the normality of data. The normally distributed data will be analyzed using an independent t-test for in-between group comparison, and a paired t-test will be used to compare the post-intervention results from the baseline values within each group. In case of skewed data, the Wilcoxon signed-rank test will be utilized for within-group comparison and the Mann-Whitney U test for between-group comparison. All statistical tests will be performed using IBM SPSS version 21.0 (IBM Corp. Armink, NY, USA). The level of statistically significant value is assumed at p-value < 0.05. Results The performance of the participants will be assessed on LEMS, the 10-m walk test, WISCI-II, SCIM-III, WHOOQOL-BREF, BBS, and kinematic and kinetic variables of gait at pre-intervention and after 15 sessions of intervention. Discussion Regaining balance and walking are among the top priorities of individuals with incomplete spinal cord injury. Retraining balance and gait in iSCI is challenging for healthcare professionals. tDCS, a non-invasive brain stimulation technique, has been shown to modulate cortical excitability and enhance motor learning, while VR-TT provides a task-oriented approach to gait training by integrating real-time feedback and interactive motor engagement. Combining two innovative approaches, we could accelerate the process of recovery among individuals with SCI. The results of this trial will provide information about the effectiveness of combined transcranial direct current stimulation and virtual reality treadmill training in improving lower extremity motor strength, balance, gait parameters, functional independence, and quality of life of individuals with spinal cord injury. This trial is designed to meet adequate methodological requirements consisting of randomization, allocation concealment, and participant blinding. The limitation of this trial is that it is a single-blinded (participants blinded) trial. The recruitment of the participant is through a convenient sampling method, and the participants will be recruited from a single center. Abbreviations SCI Spinal cord injury QoL Quality of life ROM Range of motion of joint BBS Berg Balance Scale SCIM III Spinal Cord Independence Measure III ASIA American Spinal Injury Association LEMS lower extremity motor score tDCS Transcranial direct current stimulator VRTT Virtual reality assisted treadmill training WISCI -II Walking index for spinal cord injury II Declarations Trial Status The trial is registered with the clinical trial registry. This is the first version of the protocol finalized in August 2024. The first participant in the trial was recruited in December 2024, and the expected duration of the participant’s recruitment to complete the study is approximately March 2026. Acknowledgment: The authors want to acknowledge Indian Spinal Injuries Centre (ISIC) for support in the conduction of the trial. The authors want to acknowledge Dr. Chitra Kataria, Principal, ISIC Institute of Rehabilitation Sciences; Dr. Gaurav Sachdeva, former head of the Physical Medicine & Rehabilitation Department of the Indian Spinal Injuries Center; and Dr. Hitesh Kumar, Physiotherapist, PMR Department, ISIC, for providing their valuable inputs and suggestions during the protocol development and conduction of the trial. Dissemination policy – trial results The results of the study will be shared through scientific research publications, trial registers, data-sharing arrangements, social media, and conferences. Authors Contribution All authors were involved in the conception and design of this study. The first author has prepared the protocol manuscript, and all authors contributed to the review and approval of the final manuscript. Funding – No funding or sponsor is involved with this trial. This is an investigator-initiated RCT. Availability of data and materials - Any data required to support the protocol can be provided on request by keeping participant’s identification details confidential Ethical approval and consent to participate The trial is approved by the Institutional Ethical Committee of (name of organization not mentioned here for the purpose of the blinded manuscript) with reference number. Written informed consent will be obtained from all participants. Consent for publication Not applicable – No identifying image or other personal or clinical details of the participant are presented here. Conflict of Interest No potential conflict of interest relevant to this article was reported. References Hagen EM. Acute complications of spinal cord injuries. World J Orthop. 2015;6(1):17-23. Published 2015 Jan 18. doi:10.5312/wjo.v6.i1.17. Sezer N, Akkuş S, Uğurlu FG. 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Effects of transcranial direct current stimulation alone and in combination with rehabilitation therapies on gait and balance among individuals with Parkinson’s disease: a systematic review and meta-analysis. Journal of NeuroEngineering and Rehabilitation [Internet] 2024;21(1). Available from: https://doi.org/10.1186/s12984-024-01311-2 Fleming MK, Theologis T, Buckingham R, Johansen-Berg H. Transcranial direct current stimulation for promoting motor function in cerebral palsy: a review. J Neuroeng Rehabil. 2018 Dec 20;15(1):121. doi: 10.1186/s12984-018-0476-6. PMID: 30572926; PMCID: PMC6302403. Brown GL, Brown MT. Transcranial electrical stimulation in neurological disease. Neural Regen Res. 2022 Oct;17(10):2221-2222. doi: 10.4103/1673-5374.335796. PMID: 35259838; PMCID: PMC9083147. Klamruen P, Suttiwong J, Aneksan B, Muangngoen M, Denduang C, Klomjai W. Effects of Anodal Transcranial Direct Current Stimulation with Overground Gait Training on Lower Limb Performance in Individuals with Incomplete Spinal Cord Injury. Arch Phys Med Ngernyam N, Jensen MP, Arayawichanon P, et al. The effects of transcranial direct current stimulation in patients with neuropathic pain from spinal cord injury. Clin Neurophysiol. 2015;126(2):382-390. doi:10.1016/j.clinph.2014.05.034 Evans NH, Field-Fote EC. A Pilot Study of Intensive Locomotor-Related Skill Training and Transcranial Direct Current Stimulation in Chronic Spinal Cord Injury. J Neurol Phys Ther. 2022;46(4):281-292. doi:10.1097/NPT.0000000000000403 Nijhawan M, Kataria C. Effect of Transcranial Direct Current Stimulation on Lower Extremity Muscle Strength, Quality of Life, and Functional Recovery in Individuals With Incomplete Spinal Cord Injury: A Randomized Controlled Study. Cureus. 2024 Jan 10;16(1):e51989. doi: 10.7759/cureus.51989 Cho C, Hwang W, Hwang S, Chung Y. Treadmill Training with Virtual Reality Improves Gait, Balance, and Muscle Strength in Children with Cerebral Palsy. Tohoku J Exp Med. 2016;238(3):213-218. doi:10.1620/tjem.238.213 Kržišnik M, Rauter BH, Bizovičar N. Effects of virtual reality-based treadmill training on 104 the balance and gait ability in patients after stroke: a randomized controlled trial. Hrvat Rev za Rehabil istraživanja [Internet]. 2021 Dec 23 [cited 2022 May 8];57(2):92–102. Available from: https://www.zebris. Peruzzi A, Zarbo IR, Cereatti A, Della Croce U, Mirelman A. An innovative training program based on virtual reality and treadmill: effects on gait of persons with multiple sclerosis. Disabil Rehabil [Internet]. 2017 Jul 17;39(15):1557–63. Available from: https://www.tandfonline.com/doi/full/10.1080/09638288.2016.1224935 Chan A-W, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin J, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleža-Jerić K, Laupacis A, Moher D. SPIRIT 2013 Explanation and Elaboration: Guidance for protocols of clinical trials. BMJ. 2013;346:e7586 Simis M, Fregni F, Battistella LR. Transcranial direct current stimulation combined with robotic training in incomplete spinal cord injury: a randomized, sham-controlled clinical trial. Spinal Cord Ser Cases. 2021 Sep 27;7(1):87. doi: 10.1038/s41394-021-00448-9. PMID: 34580282; PMCID: PMC8476486. Gunduz B, Erhan B. Updates in ASIA examination: Lower extremity motor examination. Türkiye Fiziksel Tıp Ve Rehabilitasyon Dergisi [Internet]. 2015 Jul 7;61(1):19–24. Available from: https://doi.org/10.5152/tftrd.2015.65632 Lemay, J. F., & Nadeau, S. (2010). Standing balance assessment in ASIA D paraplegic and tetraplegic participants: concurrent validity of the Berg Balance Scale. Spinal cord, 48(3), 245–250. https://doi.org/10.1038/sc.2009.119 Wirz, M., Müller, R., & Bastiaenen, C. (2010). Falls in persons with spinal cord injury: validity and reliability of the Berg Balance Scale. Neurorehabilitation and neural repair, 24(1), 70–77. https://doi.org/10.1177/1545968309341059 Srisim K, Saengsuwan J, Amatachaya S. Functional assessments for predicting a risk of multiple falls in independent ambulatory patients with spinal cord injury. J Spinal Cord Med. 2015 Jul;38(4):439-45. doi: 10.1179/2045772313Y.0000000186. Epub 2014 Jan 21. PMID: 24621036; PMCID: PMC4612199. Ditunno, J. F., Jr, Ditunno, P. L., Scivoletto, G., Patrick, M., Dijkers, M., Barbeau, H., Burns, A. S., Marino, R. J., & Schmidt-Read, M. (2013). The Walking Index for Spinal Cord Injury (WISCI/WISCI II): nature, metric properties, use and misuse. Spinal cord, 51(5), 346–355. https://doi.org/10.1038/sc.2013.9 Scivoletto G, Tamburella F, Laurenza L, Foti C, Ditunno JF, Molinari M. Validity and reliability of the 10-m walk test and the 6-min walk test in spinal cord injury patients. Spinal Cord. 2011 Jun;49(6):736-40. doi: 10.1038/sc.2010.180. Epub 2011 Jan 11. PMID: 21221120. Itzkovich, M., Gelernter, I., Biering-Sorensen, F., Weeks, C., Laramee, M. T., Craven, B. C., … Catz, A. (2007). The Spinal Cord Independence Measure (SCIM) version III: Reliability and validity in a multi-center international study. Disability and Rehabilitation, 29(24), 1926–1933. https://doi.org/10.1080/09638280601046302 Jang, Y., Hsieh, C. L., Wang, Y. H., & Wu, Y. H. (2004). A validity study of the WHOQOL-BREF assessment in persons with traumatic spinal cord injury. Archives of physical medicine and rehabilitation, 85(11), 1890–1895. https://doi.org/10.1016/j.apmr.2004.02.032 Supplementary Files SPIRITchecklistGarima.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Minor revision 12 Feb, 2026 Reviewers agreed at journal 17 Jul, 2025 Reviewers invited by journal 17 Jul, 2025 Editor assigned by journal 27 May, 2025 First submitted to journal 26 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6750457","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":486653172,"identity":"ae57fd11-d90f-4b57-a6b0-71f22428349d","order_by":0,"name":"Garima Wadhwa","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYJCCA0DMuIGBGURLyJCihS0BpIWHaJuAWngMQAzCWuTdzz48dKPmsOx2iZzPr27UWPAwsB8+ugGfFsMz6QaHc44dNt45I3ebdc4xoMN40tJu4NXSkMZwOIftduKG27nbjHPYgFokeMzwa+l/BtTyD6Ql55lxzj8itMhLAG3JbQNrYX6c20aEFgMJoC25ff+NN9x/Zsac2yfBw0bIL/L9acyfc76lyW44c/gxkFEnx89++Bh+Ww4g2GwSYBKfcrAtDQg28wdCqkfBKBgFo2BkAgDIglAPmhL26AAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-6885-9108","institution":"SGT University \u0026 ISIC Institute of Rehabilitation Sciences","correspondingAuthor":true,"prefix":"","firstName":"Garima","middleName":"","lastName":"Wadhwa","suffix":""},{"id":486653173,"identity":"8d2b61be-c024-4667-9a2a-9b27a88a5798","order_by":1,"name":"Pooja Anand","email":"","orcid":"","institution":"SGT University","correspondingAuthor":false,"prefix":"","firstName":"Pooja","middleName":"","lastName":"Anand","suffix":""},{"id":486653174,"identity":"c0ea7297-4fa2-4320-b745-d79b8e0d1121","order_by":2,"name":"Priyanka Rishi","email":"","orcid":"","institution":"SGT University","correspondingAuthor":false,"prefix":"","firstName":"Priyanka","middleName":"","lastName":"Rishi","suffix":""}],"badges":[],"createdAt":"2025-05-26 11:44:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6750457/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6750457/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87230349,"identity":"c5cd9be6-4249-4405-ab41-d7e851bef00f","added_by":"auto","created_at":"2025-07-21 18:38:01","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":627970,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Figure1CONSORTFlowchartpage0001.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6750457/v1/ed0b1f23d3bd738faa9f0824.jpg"},{"id":87231110,"identity":"fc21bfc7-cad5-4a4d-a48c-81d7aea094b0","added_by":"auto","created_at":"2025-07-21 18:54:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1377884,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6750457/v1/db52f9f9-5853-4f1c-9ea8-d238c0cee5e0.pdf"},{"id":87230227,"identity":"46c17fc8-b70f-4c85-98b4-7283a69f31fc","added_by":"auto","created_at":"2025-07-21 18:30:01","extension":"pdf","order_by":11,"title":"","display":"","copyAsset":false,"role":"supplement","size":210141,"visible":true,"origin":"","legend":"","description":"","filename":"SPIRITchecklistGarima.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6750457/v1/10210300f7bfca77f0de678b.pdf"}],"financialInterests":"","formattedTitle":"Optimizing Motor Functions in Incomplete Spinal Cord Injury with Simultaneous Application of Transcranial Direct Current Stimulation and Virtual Reality Assisted Treadmill Training: A Study Protocol for a Randomized Controlled Trail","fulltext":[{"header":"Background","content":"\u003cp\u003eSpinal cord injury (SCI) is a devastating form of disability causing temporary or permanent loss of motor, sensory, or autonomic functions below the level of injury [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Individuals with spinal cord injuries tend to develop severe complications in the physical, psychological, and social domains. The physical impairments may range from spinal or musculoskeletal deformities due to disturbances in muscle balance, spasticity, or the development of contractures. The psychosocial issues involving fatigue, tiredness, mood disorders, or depression are also commonly encountered in this population [\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMoreover, the disruption of communication between the brain and the lower extremities impedes the initiation and execution of purposeful movements that are required for balance, ambulation, and functional activities [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The coordination and integration of visual, vestibular, and proprioceptive feedback, as well as reflexive limb control, results in a balanced body [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Impairments in muscle strength, muscle tone, and sensory systems lead to a loss of balance [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Poor balance is a major cause of falls among individuals with spinal cord injuries [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Falls can result in injuries such as fractures, bruises, and ulcers, which may further complicate the rehabilitation process. Beyond physical injury, the fear of falling can lead to reduced activity participation, social withdrawal, and decreased confidence in performing daily tasks.\u003c/p\u003e\u003cp\u003eAdditionally, individuals with SCI tend to develop slow, inefficient, unbalanced, or uncoordinated gait patterns. They usually walk slowly, with a long cycle time and little strides [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Lemay et al. (2015) showed that the most critical and challenging situations for patients with incomplete SCI are the initiation and termination of gait. More specifically, gait initiation and termination occur at slower speeds, and in comparison, termination of gait is more challenging than initiation of gait [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Regaining walking abilities has been considered the topmost priority and a major challenge of rehabilitation for individuals with spinal cord injury. Various approaches, including virtual reality [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], partial body weight support treadmill training [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], overground training, and robotic training, have shown promising results in improving the balance and gait of individuals with spinal cord injury [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, no one approach has been found to be superior to the other.\u003c/p\u003e\u003cp\u003eThe growing body of research is emphasizing the role of neuromodulation, including transcranial direct current stimulation alone or in adjunct with other therapies. Recent evidence has explored the beneficial effects of transcranial stimulation on locomotor functions and upper extremity functions among individuals with neurological disorders [\u003cspan additionalcitationids=\"CR21 CR22 CR23\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The application of transcranial direct current stimulation among individuals with spinal cord injury has been tested for improving motor functions and locomotion and for reducing neuropathic pain [\u003cspan additionalcitationids=\"CR26 CR27\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, the available evidence has shown mixed results for individuals with SCI. The recent study by Klaumren (2024) noted significant improvement of tDCS on the walking speed of individuals with SCI when it was applied in conjunction with overground walking [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In contrast, the study by Evans [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] and Nijhawan [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] did not find any addictive effect of tDCS on walking speed and quality of life, respectively, of individuals with spinal cord injury.\u003c/p\u003e\u003cp\u003eAnother innovative approach that has been hypothesized to enhance neuroplasticity is the combination of virtual reality along with treadmill training (VR-TT). The virtual reality system enhances the engagement of individuals by providing an interactive environment, while the treadmill offers a high-intensity, controlled, and repetitive movement pattern. The use of VR-TT in gait and balance training has demonstrated improvements in motor control and functional mobility in individuals with neurological impairments, including stroke, cerebral palsy, and multiple sclerosis [\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eGiven the individual benefits of tDCS and VRTT in promoting motor function recovery, their simultaneous application holds the potential to achieve synergistic effects and functional outcomes in incomplete spinal cord injury (iSCI) rehabilitation. Considering the utmost importance of regaining balance and ambulatory function in iSCI, this study aims to evaluate the efficacy of the simultaneous application of tDCS and VRTT in optimizing motor function recovery in individuals with iSCI. This may provide a new, evidence-supported approach to improving balance and gait outcomes and overall functional independence of individuals with iSCI.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe aim of the proposed study is to evaluate the synergistic effect of transcranial direct current stimulation and virtual reality-assisted treadmill training on the motor functions and quality of life of individuals with incomplete spinal cord injury.\u003c/p\u003e\u003cp\u003eStudy Design\u003c/p\u003e\u003cp\u003eA prospective, single-blind, parallel two-group randomized controlled design with equal allocation (1:1) will be undertaken.\u003c/p\u003e\u003cp\u003eSetting of the study\u003c/p\u003e\u003cp\u003e A convenient sample of 52 participants with incomplete spinal cord injury will be recruited from the in-patient and out-patient physical medicine and rehabilitation (PMR) department of the Indian Spinal Injuries Center, New Delhi, India\u003c/p\u003e\u003cp\u003eParticipants\u003c/p\u003e\u003cp\u003e All participants will be provided with the information sheets, and written consent will be obtained by the principal investigator before recruitment. The participants will be selected based on the eligibility criteria mentioned in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Medical clearance will be taken for all participants before enrollment into the intervention. This research protocol is consistent with the current Consolidated Standards of Reporting Trials (CONSORT) guidelines (Fig.\u0026nbsp;1) and is developed in accordance with the Standard Protocol Items: Recommendations for Interventional Trails (SPIRIT Schedule) [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) and the SPIRIT checklist are attached in additional file 1. A visual description of the study regarding enrollment, assessment, and intervention is depicted in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Baseline assessment (T0) will be done before allocation, and post-intervention assessment (T1) will be taken after 15 intervention sessions, which will serve to compare the short-term effect of the respective intervention. The DRC and IEC Committees of (\u0026hellip; name is not mentioned here for the purpose of blind review; it will be added later) maintain track of all potential recruiters and monitor data collection during the intervention. The members of the DRC, along with the consultants and physiotherapists in the hospital, provide day-to-day support to all aspects of the local organization of the trial. The guides and co-guides are in charge of the trial and supervise the trial frequently.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u0026ndash; Eligibility Criteria\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eEligibility Criteria\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInclusion Criteria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTraumatic or non-traumatic incomplete spinal cord injury.\u003c/p\u003e\u003cp\u003eCategorized as American Spinal Injury-Association Impairment Scale Grade C and D.\u003c/p\u003e\u003cp\u003eLevel of injury from T1 to L2\u0026nbsp;.\u003c/p\u003e\u003cp\u003eAge between 18\u0026ndash;65 years.\u003c/p\u003e\u003cp\u003eAt least 3 months after SCI.\u003c/p\u003e\u003cp\u003eFunctional ambulatory category - \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e 3.\u003c/p\u003e\u003cp\u003eIndividuals with SCI able to advance leg independently with the treadmill speed at 0.2 km per hour.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExclusion Criteria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAny other pre-existing neurological problem, musculoskeletal condition, cardiovascular or psychiatric problem which may interfere with the treatment.\u003c/p\u003e\u003cp\u003eSpasticity of grade 3 or more in lower extremities on Modified Ashworth Scale which may interfere with the treatment.\u003c/p\u003e\u003cp\u003eVisual or auditory impairment such that it impacts on the ability to participate.\u003c/p\u003e\u003cp\u003eBody Weight more than 150 kg.\u003c/p\u003e\u003cp\u003eSkin lesions or rash at potential sites which may interfere with the treatment or placing of electrodes of transcranial direct current stimulation or Grade 2 or higher-pressure ulcers (according to the National Pressure Ulcer Advisory Panel classification) that interfered with harness support or walking or standing.\u003c/p\u003e\u003cp\u003eHistory of seizure, migraine, headache or epilepsy, brain surgery.\u003c/p\u003e\u003cp\u003eHistory of recent episode of orthostatic hypotension or autonomic dysreflexia.\u003c/p\u003e\u003cp\u003eCardiac pace-maker.\u003c/p\u003e\u003cp\u003ePregnancy.\u003c/p\u003e\u003cp\u003eIntracranial or skull implants.\u003c/p\u003e\u003cp\u003ePrevious experience of transcranial direct current stimulation or VR assisted treadmill training post SCI.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSchedule of enrollment, interventions and assessments according to the Standard Protocol Items: Recommendations for Interventional Trials Guideline\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEnrollment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAllocation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003cp\u003e(T0)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIntervention\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePost- Intervention assessment (T1)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEnrollment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Eligibility Screen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Informed Consent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Medical Clearance\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Allocation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInterventions\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Active tDCS\u0026thinsp;+\u0026thinsp;VR-TT group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Sham tDCS\u0026thinsp;+\u0026thinsp;VR-TT group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAssessments\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Functional Ambulatory Category\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Walking index for spinal cord injury\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Lower Extremity Motor Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Technobody Walker view Gait assessment\u003c/p\u003e\u003cp\u003e\u0026bull; Step length (RT and LT side)\u003c/p\u003e\u003cp\u003e\u0026bull; ROM of Hip joint (RT and LT side)\u003c/p\u003e\u003cp\u003e\u0026bull; ROM of knee joint (RT and LT side)\u003c/p\u003e\u003cp\u003e\u0026bull; Average Range of trunk flexion- extension\u003c/p\u003e\u003cp\u003e\u0026bull; Average range of trunk Lateral flexion\u003c/p\u003e\u003cp\u003e\u0026bull; Vertical Displacement of COG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Berg Balance Scale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Functional Reach Test\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- 10- meter Walk test\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- SCIM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- WHO-QOL BREF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eActive tDCS\u0026thinsp;+\u0026thinsp;VR-TT group, Active transcranial direct current stimulation and virtual reality treadmill training group; Sham tDCS\u0026thinsp;+\u0026thinsp;VR-TT group, Shan transcranial direct current stimulation and virtual reality assisted treadmill training group; RT, Right side; LT, Left side; ROM, range of motion of joint; COG, center of gravity, SCIM, Spinal cord Independence Measure, WHO-QOL BREF, World Health Organization- Quality of life -BREF scale.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eEthical Consideration\u003c/p\u003e\u003cp\u003e The study received approval from the ethical committee of the organization (the name is not mentioned here for the purpose of blind review; it will be added later) under the protocol number (ISIC/RP/2024/032) and is registered with the Clinical Trials Registry (number will be added later, kept anonyms for blind review). The participants will be informed orally and in writing about the purpose of this trial, benefits of participation, potential risk, and rights to withdraw from the trial at any point during the study before the screening. The data of the participants will be collected, documented, and managed confidentially. The authors related to the trial will have access to the final trial dataset.\u003c/p\u003e\u003cp\u003eTermination Criteria\u003c/p\u003e\u003cp\u003eThe intervention will be terminated immediately if any signs or symptoms of autonomic dysreflexia are observed in participants or if any kind of uneasiness is reported by the participants.\u003c/p\u003e\u003cp\u003eSample Size\u003c/p\u003e\u003cp\u003eA priori sample size estimation was done using the statistical formula mentioned below by considering the Waking Index for Spinal Cord Injury (WISCI II) scale as the primary outcome measure. The data used for calculation was based on the study carried out by Simis et al. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. The alpha value was kept at 0.05 at 80% power and with a 10% dropout rate. The total calculated sample size comes out to be 52 (26 in each group).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eFormula used for sample size calculation:\u003c/h2\u003e\u003cp\u003e\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:\\text{n}=\\frac{({{\\sigma\\:}}_{1}^{2}+{{\\sigma\\:}}_{2}^{2}){{(\\text{Z}}_{1-\\propto\\:/2}\\:+{\\text{Z}}_{1-{\\beta\\:}})}^{2}}{{\\text{d}}^{2}}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eRandomization\u003c/p\u003e\u003cp\u003eEligible candidates will be assigned randomly to either the active anodal intervention group (active transcranial direct current stimulation along with virtual reality-assisted treadmill training) or the sham interventional group (sham transcranial direct current stimulation and virtual reality-assisted treadmill training) with a 1:1 allocation. Randomization will be performed using a computer-generated randomization sequence defined by random allocation software 2.0. Randomization and group allocation will be carried out by a blinded investigator.\u003c/p\u003e\u003cp\u003eAllocation Concealment\u003c/p\u003e\u003cp\u003eThe allocation schedule will be sequentially marked as Group A\u0026mdash;active transcranial direct current stimulation with virtual reality-assisted treadmill training and as Group B\u0026mdash;sham transcranial direct current stimulation with virtual reality-assisted treadmill training and will be sealed in opaque envelopes to ensure concealment. Furthermore, an individual not associated with this study will sequentially open the concealed envelopes to reveal the participants' group allocation. The principal investigator will be informed of the group allocation given the nature of the intervention.\u003c/p\u003e\u003cp\u003eBlinding\u003c/p\u003e\u003cp\u003eThe trial is a single blinded study where the participant will be blinded to group allocation. Also, the statistician who will analyze the data would be unaware of the identification of treatment groups.\u003c/p\u003e\u003cp\u003eDescription of the Devices \u0026ndash;\u003c/p\u003e\u003cp\u003eTranscranial direct current stimulator\u0026mdash;Caputron Brain Premier tDCS Device E1 will be used. It is an anodal and cathodal monophasic current device. Wet-type sponge surface electrodes (1.5 inches in diameter) soaked in saline will be employed. Rubber straps will be used to securely place the electrodes on the skin surface.\u003c/p\u003e\u003cp\u003eVirtual Reality Assisted Treadmill Trainer\u0026mdash;For virtual reality-assisted treadmill training and for gait assessment, \u0026ldquo;Walker View TM, Techno Body\u0026rdquo; will be used. The treadmill is equipped with a sensorized belt with 8 load cells that detect the patient load, a motion capture 3D camera, a speed control system, and a 49\u0026rdquo; wide LCD screen (liquid crystal display screen). It provides complete gait analysis through a 3D camera and load cells. The walking speed can be set in the range of 0\u0026ndash;20 km/hr, with incremental speed of 0.2 km/hr. The system has integrated software\u0026mdash;the Technobody management system.\u003c/p\u003e\u003cp\u003eIntervention and Duration\u003c/p\u003e\u003cp\u003eTranscranial direct current stimulation\u0026mdash;The anodal electrode will be placed over the primary motor cortex M1 region according to the international 10\u0026ndash;20 electroencephalogram standardized system. The cathodal electrode will be placed over the supraorbital region contralateral to the anodal electrode. A constant 2 mA direct current will be delivered in the anodal group with a gradual current ramp-up and ramp-down of 30 seconds. The intensity and duration were selected based on the previous studies demonstrating these parameters to be safe [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. The electrode placement for the sham group will be similar. However, the participant will only receive current for the initial 30 seconds, and then the power will be turned off for the remaining period.\u003c/p\u003e\u003cp\u003eVR-Assisted treadmill training\u0026mdash;Participants need to walk on the walker view treadmill with the initial speed of 0.2 km/hr while viewing a virtual screen placed in front of the treadmill. The participant needs to walk for 20 minutes in each session. The intervention will be the same for Group A and Group B. The virtual screen progression is divided into three phases. Individuals in either group will receive 15 sessions over a span of three weeks. Individuals will also receive individualized conventional physiotherapy sessions. The details of the intervention are described in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDetails of the intervention in each group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntervention\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDetails of Intervention\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eTranscranial direct current stimulation (1 to 15 sessions)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Active tDCS\u0026thinsp;+\u0026thinsp;VR- TT Group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLocation - Anode- Primary motor area- M1\u003c/p\u003e\u003cp\u003eCathode- supra-orbital area\u003c/p\u003e\u003cp\u003eIntensity \u0026minus;\u0026thinsp;2MA,\u003c/p\u003e\u003cp\u003e(Initial 30 seconds- ramp up, last 30 seconds- ramp down)\u003c/p\u003e\u003cp\u003eDuration- 20 Minutes (10 minutes each hemisphere)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Sham tDCS\u0026thinsp;+\u0026thinsp;VR-TT Group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLocation - Anode- Primary motor area- M1\u003c/p\u003e\u003cp\u003eCathode- supra-orbital area\u003c/p\u003e\u003cp\u003eIntensity \u0026ndash; Initial 30 seconds Ramp up to 2 MA, then switched off\u003c/p\u003e\u003cp\u003eDuration- 20 Minutes (10 minutes each hemisphere)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVirtual Reality Assisted Treadmill Training \u0026ndash; Same for both groups\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDescription\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eParticipants need to walk over the treadmill with initial speed of 0.2 kn/ hr. The virtual screen Infront of the treadmill will be progressed in three phases mentioned below\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u003cb\u003eProgression of the virtual screen\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003ePhase 1\u003c/b\u003e (1-\u0026ndash; 5 sessions)- Visual feedback mode with sensor activation and Foot steps tiles\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003ePhase 2\u003c/b\u003e (6\u0026ndash;10 sessions)Virtual reality slow moving VR scenes (that depicts the view of park/ city levels)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003ePhase 3\u003c/b\u003e (11\u0026ndash;15 sessions) -Virtual reality video mode with distractions\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eProgression of the treadmill\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e- Starting speed 0.2km/hr increased on individual basis.\u003c/p\u003e\u003cp\u003e- If patient is able to maintain correct body alignment at 0.8km/hr speed, 1% inclination will be done.\u003c/p\u003e\u003cp\u003e- Participant can take side bars support but encouraged to reduce support.\u003c/p\u003e\u003cp\u003e- No overweighing harness done i..e no partial weight upliftment done. However for initial sessions harness was used for fall protection if needed.\u003c/p\u003e\u003cp\u003e- AFO\u0026rsquo;s/ Braces allowed while walking if required\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eConventional Rehabilitation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePhysiotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIndividualized structured physiotherapy sessions consisting of range of motion of joint exercises, strengthening exercises, stretching of spastic muscles, sitting balance training, core training etc\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAdherence\u003c/p\u003e\u003cp\u003eThe adherence of the participants to the training protocol will be monitored through documentation of participants\u0026rsquo; attendance in sessions. In accordance with the \"intention-to-treat\" principle, if the participants are unable to complete all of the sessions within the allotted three weeks, they may extend the training period by one week. The nature, scope, and trend of missing data throughout the investigation are also clearly disclosed by the authors.\u003c/p\u003e\u003cp\u003eOutcome Measure Assessment and procedure to measure\u003c/p\u003e\u003cp\u003e1)\u0026nbsp; \u0026nbsp;Strength Assessment\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The lower extremity motor score (LEMS), a subscale of the American Spinal Injury Association (ASIA) classification, will be utilized to measure the strength of the lower extremity key muscles in accordance with the standard neurological assessment developed by ASIA. The strength of the muscle is graded on a 6-point scale ranging from total paralysis (0) to normal active movement with a full range of motion against gravity and full resistance (5). The total LEMS score is calculated by adding the bilateral lower extremity key muscle power with a total possible score of 50. \u0026nbsp; The five key muscles include hip flexors, knee extensors, ankle dorsiflexors, long toe extensors, and ankle plantar flexors of each leg [34].\u003c/p\u003e\n\u003cp\u003e2)\u0026nbsp; \u0026nbsp;Balance Assessment\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBerg Balance Scale: The Berg Balance Scale (BBS) is a clinical measure of balance consisting of 14 tasks of progressing difficulty. Each task is graded on a five-point ordinal scale with 0 indicating the lowest degree of function and 4 indicating the highest level of function. The total number of points that can be earned ranges from 0 to 56. The ability to complete the tasks without help and to meet time or distance requirements determines the score. The BBS has shown to have excellent inter-rater (ICC 0.98) and intra-rater reliability (ICC 0.97) [35, 36].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFunctional Reach test: At the height of the subject\u0026apos;s acromion process, a leveled yardstick will be affixed to the wall to measure the reaching distance. Participants will be asked to make a fist and extend their arm forward (position 1), and the placement of the end of the third metacarpal along the yardstick will be recorded. Subjects will then need to reach as far forward as they can without losing their balance or taking a step (position 2), and the placement of the end of the third metacarpal will again be recorded. Functional reach distance will be measured as the mean difference between positions 1 and 2 over three trials [37].\u003c/p\u003e\n\u003cp\u003e3)\u0026nbsp; \u0026nbsp;Gait Assessment\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eKinematic and kinetic parameters of gait: The TechnoBody Walker view treadmill system will be employed for assessment of kinetic and kinematic parameters of the participant\u0026rsquo;s gait cycle. To begin with analysis, the therapist selects gait analysis from the test icon and then selects the neurologic module from the options. The test speed will be kept constant at 0.2km/h and the duration at 2 minutes for every participant and at each test (pre- and post-). The walker view proprietary software calculates spatiotemporal gait parameters and kinematic variables automatically, including average cycle time (cycles/seconds), left and right step length (measured in centimeters), left and right hip range of motion of joint (measured in degrees), left and right knee ROM (measured in degrees), trunk flexion-extension ROM (measured in degrees), trunk lateral flexion ROM (measured in degrees), vertical displacement of Center of Gravity (measured in centimeters), and load symmetry (measured in %), and the treadmill program generates a report for each trial, which will then be used in data analysis.\u003c/p\u003e\n\u003cp\u003eWalking Ability: Walking Index for Spinal Cord Injury II (WISCI -II) will be used for assessment of the walking ability of the participants. It employs an ordinal scale with 21 levels. This scale assesses walking ability based on the need for physical assistance, braces, and walking aids. The individual needs to walk a distance of 10 meters. The maximum level at which walking is safe will be assessed, with 0 indicating no walking and 20 indicating unlimited walking. Furthermore, in the SCI population, it has been demonstrated to have outstanding inter- and intra-rater reliability (1.00) and repeatability (ICC, 0.995) [38].\u003c/p\u003e\n\u003cp\u003eWalking Speed: 10-Meter A walk test will be administered for walking speed. Participants will be asked to walk with/without an assistive device independently for 10 meters. The observation in the intermediate 6 meters will be recorded. The duration in seconds will be recorded under preferred speed and fast speed scenarios. Three trials will be performed, and the average of the three trials will be used for analysis. The 10-meter walk test has high inter- and intra-rater reliability [39].\u003c/p\u003e\n\u003cp\u003e4)\u0026nbsp; \u0026nbsp;Functional Assessment\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe Spinal Cord Independence Measure\u0026mdash;a self-report measure\u0026mdash;will be used for functional performance assessment. It consists of 19 items under three domains, i.e., self-care, respiration and sphincter management, and mobility. Scores will be higher for those who are able to complete the activities mentioned with less assistance, aids, or medical compromise. The total scoring of the scale ranges from 0 to 100. The SCIM III has been found to be an excellent measure for functional independence for individuals with spinal cord injury with an interclass correlation of 0.94 and a Cronbach alpha value of 0.70 [40].\u003c/p\u003e\n\u003cp\u003e5)\u0026nbsp; \u0026nbsp;Quality of Life\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe World Health Organization Quality of Life-BREF (WHOQOL BREF) is a 26-item scale covering the four domains, including physical health, psychological health, and social and environmental domains. Participants need to rate the intensity of selected attributes of QOL as per the previous 2 weeks on a 5-point Likert response scale for every item. The mean score will be obtained as per the criteria to compute the mean of the transformed score from each domain. In people with SCI, all WHOQOL-BREF domains have been found to exhibit strong internal consistency (Cronbach \u0026alpha; range, 0.74\u0026ndash;0.78), with the exception of the social interactions category (\u0026alpha;=0.54) [41].\u003c/p\u003e\n\u003cp\u003eStatistical Analysis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe student t-test for numerical variables will be used to check if the randomization process created between groups has participants with homogeneous clinical characteristics before the intervention, thereby avoiding potential selection bias.\u003c/p\u003e\n\u003cp\u003eCharacteristics of participants will be descriptively summarized for age, gender, time since injury, level of injury, ambulatory level, etc., using mean, standard deviation, or frequency. The Shapiro-Wilk test will be used to know the normality of data. The normally distributed data will be analyzed using an independent t-test for in-between group comparison, and a paired t-test will be used to compare the post-intervention results from the baseline values within each group. In case of skewed data, the Wilcoxon signed-rank test will be utilized for within-group comparison and the Mann-Whitney U test for between-group comparison. All statistical tests will be performed using IBM SPSS version 21.0 (IBM Corp. Armink, NY, USA). The level of statistically significant value is assumed at p-value \u0026lt; 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe performance of the participants will be assessed on LEMS, the 10-m walk test, WISCI-II, SCIM-III, WHOOQOL-BREF, BBS, and kinematic and kinetic variables of gait at pre-intervention and after 15 sessions of intervention.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRegaining balance and walking are among the top priorities of individuals with incomplete spinal cord injury. Retraining balance and gait in iSCI is challenging for healthcare professionals. tDCS, a non-invasive brain stimulation technique, has been shown to modulate cortical excitability and enhance motor learning, while VR-TT provides a task-oriented approach to gait training by integrating real-time feedback and interactive motor engagement. Combining two innovative approaches, we could accelerate the process of recovery among individuals with SCI. The results of this trial will provide information about the effectiveness of combined transcranial direct current stimulation and virtual reality treadmill training in improving lower extremity motor strength, balance, gait parameters, functional independence, and quality of life of individuals with spinal cord injury. This trial is designed to meet adequate methodological requirements consisting of randomization, allocation concealment, and participant blinding. The limitation of this trial is that it is a single-blinded (participants blinded) trial. The recruitment of the participant is through a convenient sampling method, and the participants will be recruited from a single center.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eSCI Spinal cord injury \u003c/p\u003e\n\u003cp\u003eQoL Quality of life \u003c/p\u003e\n\u003cp\u003eROM Range of motion of joint \u003c/p\u003e\n\u003cp\u003eBBS Berg Balance Scale \u003c/p\u003e\n\u003cp\u003eSCIM III Spinal Cord Independence Measure III\u003c/p\u003e\n\u003cp\u003eASIA American Spinal Injury Association\u003c/p\u003e\n\u003cp\u003eLEMS lower extremity motor score\u003c/p\u003e\n\u003cp\u003etDCS Transcranial direct current stimulator\u003c/p\u003e\n\u003cp\u003eVRTT Virtual reality assisted treadmill training \u003c/p\u003e\n\u003cp\u003eWISCI -II Walking index for spinal cord injury II\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eTrial Status\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe trial is registered with the clinical trial registry. This is the first version of the protocol finalized in August 2024. The first participant in the trial was recruited in December 2024, and the expected duration of the participant\u0026rsquo;s recruitment to complete the study is approximately March 2026.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u0026nbsp;\u003c/strong\u003eThe authors want to acknowledge Indian Spinal Injuries Centre (ISIC) for support in the conduction of the trial. The authors want to acknowledge Dr. Chitra Kataria, Principal, ISIC Institute of Rehabilitation Sciences; Dr. Gaurav Sachdeva, former head of the Physical Medicine \u0026amp; Rehabilitation Department of the Indian Spinal Injuries Center; and Dr. Hitesh Kumar, Physiotherapist, PMR Department, ISIC, for providing their valuable inputs and suggestions during the protocol development and conduction of the trial.\u003c/p\u003e\n\n\u003cp\u003eDissemination policy \u0026ndash; trial results\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe results of the study will be shared through scientific research publications, trial registers, data-sharing arrangements, social media, and conferences.\u003c/p\u003e\n\u003cp\u003eAuthors Contribution\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors were involved in the conception and design of this study. The first author has prepared the protocol manuscript, and all authors contributed to the review and approval of the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFunding \u0026ndash; No funding or sponsor is involved with this trial. This is an investigator-initiated RCT.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials -\u003c/p\u003e\n\u003cp\u003eAny data required to support the protocol can be provided on request by keeping participant\u0026rsquo;s identification details confidential\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEthical approval and consent to participate\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe trial is approved by the Institutional Ethical Committee of (name of organization not mentioned here for the purpose of the blinded manuscript) with reference number. Written informed consent will be obtained from all participants.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable \u0026ndash; No identifying image or other personal or clinical details of the participant are presented here.\u003c/p\u003e\n\u003cp\u003eConflict of Interest\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo potential conflict of interest relevant to this article was reported. \u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHagen EM. Acute complications of spinal cord injuries. World J Orthop. 2015;6(1):17-23. Published 2015 Jan 18. doi:10.5312/wjo.v6.i1.17.\u003c/li\u003e\n\u003cli\u003eSezer N, Akkuş S, Uğurlu FG. Chronic complications of spinal cord injury. World J Orthop. 2015;6(1):24-33. Published 2015 Jan 18. doi:10.5312/wjo.v6.i1.24.\u003c/li\u003e\n\u003cli\u003eRahimi-Movaghar V, Sayyah MK, Akbari H, et al. Epidemiology of traumatic spinal cord injury in developing countries: A systematic review. Neuroepidemiology. 2013;41(2):65\u0026ndash;85. doi:10.1159/000350710.\u003c/li\u003e\n\u003cli\u003eNas K, Yazmalar L, Şah V, Aydın A, \u0026Ouml;neş K. Rehabilitation of spinal cord injuries. World J Orthop. 2015;6(1):8\u0026ndash;16. doi:10.5312/wjo.v6.i1.8\u003c/li\u003e\n\u003cli\u003e\u0026Ouml;zdemir F, Biruni A, Tıp \u0026Uuml;, et al. Rehabilitation for patients with paraplegia. J Turkish Spinal Surg. 2016;185(3):185\u0026ndash;194. \u003c/li\u003e\n\u003cli\u003eWijesuriya N, Tran Y, Middleton J, Craig A. Impact of fatigue on the health-related quality of life in persons with spinal cord injury. Arch Phys Med Rehabil. 2012;93(2):319\u0026ndash;324. doi:10.1016/j.apmr.2011.09.008\u003c/li\u003e\n\u003cli\u003eCraig A, Tran Y, Middleton J. Psychological morbidity and spinal cord injury: A systematic review. Spinal Cord. 2009;47(2):108\u0026ndash;114. doi:10.1038/sc.2008.115\u003c/li\u003e\n\u003cli\u003eMarkus Wirz, Hubertus J.A. van Hedel, Chapter 24 - Balance, gait, and falls in spinal cord injury. Handbook of Clinical Neurology, Elsevier, Volume 159, 2018, Pages 367-384, ISSN 0072-9752, ISBN 9780444639165, https://doi.org/10.1016/B978-0-444-63916-5.00024-0.\u003c/li\u003e\n\u003cli\u003eVan Der Salm, A., Nene, A. V., Maxwell, D. J., Veltink, P. H., Hermens, H. J., \u0026amp; IJzerman, M. J. (2005). Gait Impairments in a Group of Patients With Incomplete Spinal Cord Injury and Their Relevance Regarding Therapeutic Approaches Using Functional Electrical Stimulation. Artificial Organs, 29(1), 8\u0026ndash;14. https://doi.org/10.1111/j.1525-1594.2004.29004.x\u003c/li\u003e\n\u003cli\u003eDebenham, M. I. B., Franz, C. K., \u0026amp; Berger, M. J. (2024). Neuromuscular consequences of spinal cord injury: New mechanistic insights and clinical considerations. Muscle \u0026amp; Nerve. https://doi.org/10.1002/mus.28070\u003c/li\u003e\n\u003cli\u003eMacKinnon CD. Sensorimotor anatomy of gait, balance, and falls. Handb Clin Neurol. 2018;159:3-26. doi: 10.1016/B978-0-444-63916-5.00001-X. \u003c/li\u003e\n\u003cli\u003eNoamani A, Lemay JF, Musselman KE, Rouhani H. Characterization of standing balance after incomplete spinal cord injury: Alteration in integration of sensory information in ambulatory individuals. Gait Posture. 2021;83:152-159. doi:10.1016/j.gaitpost.2020.10.027\u003c/li\u003e\n\u003cli\u003eLee GE, Bae H, Yoon TS, Kim JS, Yi TI, Park JS. Factors that Influence Quiet Standing Balance of Patients with Incomplete Cervical Spinal Cord Injuries. Ann Rehabil Med. 2012 Aug;36(4):530-7. doi: 10.5535/arm.2012.36.4.530. \u003c/li\u003e\n\u003cli\u003eWannapakhe J, Arrayawichanon P, Saengsuwan J, Amatachaya S. Medical complications and falls in patients with spinal cord injury during the immediate phase after completing a rehabilitation program. J Spinal Cord Med. 2015 Jan;38(1):84-90. doi: 10.1179/2045772313Y.0000000173. \u003c/li\u003e\n\u003cli\u003eBarbeau H, Ladouceq M. Walking After Spinal Cord Injury\u0026thinsp;: and Functional Recovery. Archiv. 1999;80:225\u0026ndash;35. 59.\u003c/li\u003e\n\u003cli\u003eLemay JF, Duclos C, Nadeau S, Gagnon DH. Postural control during gait initiation and termination of adults with incomplete spinal cord injury. Hum Mov Sci. 2015;41(February):20\u0026ndash;31.\u003c/li\u003e\n\u003cli\u003eAbou L, Malala VD, Yarnot R, Alluri A, Rice LA. Effects of Virtual Reality Therapy on Gait and Balance Among Individuals With Spinal Cord Injury: A Systematic Review and Meta-analysis. Neurorehabil Neural Repair [Internet]. 2020 May 1 [cited 2022 May 6];34(5):375\u0026ndash;88. Available from: https://journals.sagepub.com/doi/full/10.1177/1545968320913515\u003c/li\u003e\n\u003cli\u003eMehrholz, J., Harvey, L., Thomas, S. et al. Is body-weight-supported treadmill training or robotic-assisted gait training superior to overground gait training and other forms of physiotherapy in people with spinal cord injury? A systematic review. Spinal Cord 55, 722\u0026ndash;729 (2017).\u003c/li\u003e\n\u003cli\u003eWalia, S., Kumar, P., \u0026amp; Kataria, C. (2023). Interventions to Improve Standing Balance in Individuals With Incomplete Spinal Cord Injury: A Systematic Review and Meta-Analysis. Topics in spinal cord injury rehabilitation, 29(2), 56\u0026ndash;83. https://doi.org/10.46292/sci21-00065\u003c/li\u003e\n\u003cli\u003eNavarro-L\u0026oacute;pez V, Molina-Rueda F, Jim\u0026eacute;nez-Jim\u0026eacute;nez S, Alguacil-Diego IM, Carratal\u0026aacute;-Tejada M. Effects of Transcranial Direct Current Stimulation Combined with Physiotherapy on Gait Pattern, Balance, and Functionality in Stroke Patients. A Systematic Review. Diagnostics (Basel). 2021 Apr 5;11(4):656. doi: 10.3390/diagnostics11040656. PMID: 33916442; PMCID: PMC8066876\u003c/li\u003e\n\u003cli\u003eYu L, Chen H, Chen C, Lin Y, Huang Z, Wang J, et al. Efficacy of Anodal Transcranial Direct Current Stimulation for Upper Extremity Function after Ischemic Stroke: A Systematic Review of Parallel Randomized Clinical Trials. Journal of Stroke and Cerebrovascular Diseases [Internet] 2024;34(1):108112. Available from: https://doi.org/10.1016/j.jstrokecerebrovasdis.2024.108112\u003c/li\u003e\n\u003cli\u003eNguyen TXD, Mai PT, Chang YJ, Hsieh TH. Effects of transcranial direct current stimulation alone and in combination with rehabilitation therapies on gait and balance among individuals with Parkinson\u0026rsquo;s disease: a systematic review and meta-analysis. Journal of NeuroEngineering and Rehabilitation [Internet] 2024;21(1). Available from: https://doi.org/10.1186/s12984-024-01311-2\u003c/li\u003e\n\u003cli\u003eFleming MK, Theologis T, Buckingham R, Johansen-Berg H. Transcranial direct current stimulation for promoting motor function in cerebral palsy: a review. J Neuroeng Rehabil. 2018 Dec 20;15(1):121. doi: 10.1186/s12984-018-0476-6. PMID: 30572926; PMCID: PMC6302403.\u003c/li\u003e\n\u003cli\u003eBrown GL, Brown MT. Transcranial electrical stimulation in neurological disease. Neural Regen Res. 2022 Oct;17(10):2221-2222. doi: 10.4103/1673-5374.335796. PMID: 35259838; PMCID: PMC9083147.\u003c/li\u003e\n\u003cli\u003eKlamruen P, Suttiwong J, Aneksan B, Muangngoen M, Denduang C, Klomjai W. Effects of Anodal Transcranial Direct Current Stimulation with Overground Gait Training on Lower Limb Performance in Individuals with Incomplete Spinal Cord Injury. Arch Phys Med\u003c/li\u003e\n\u003cli\u003eNgernyam N, Jensen MP, Arayawichanon P, et al. The effects of transcranial direct current stimulation in patients with neuropathic pain from spinal cord injury. Clin Neurophysiol. 2015;126(2):382-390. doi:10.1016/j.clinph.2014.05.034\u003c/li\u003e\n\u003cli\u003eEvans NH, Field-Fote EC. A Pilot Study of Intensive Locomotor-Related Skill Training and Transcranial Direct Current Stimulation in Chronic Spinal Cord Injury. J Neurol Phys Ther. 2022;46(4):281-292. doi:10.1097/NPT.0000000000000403\u003c/li\u003e\n\u003cli\u003eNijhawan M, Kataria C. Effect of Transcranial Direct Current Stimulation on Lower Extremity Muscle Strength, Quality of Life, and Functional Recovery in Individuals With Incomplete Spinal Cord Injury: A Randomized Controlled Study. Cureus. 2024 Jan 10;16(1):e51989. doi: 10.7759/cureus.51989\u003c/li\u003e\n\u003cli\u003eCho C, Hwang W, Hwang S, Chung Y. Treadmill Training with Virtual Reality Improves Gait, Balance, and Muscle Strength in Children with Cerebral Palsy. Tohoku J Exp Med. 2016;238(3):213-218. doi:10.1620/tjem.238.213\u003c/li\u003e\n\u003cli\u003eKrži\u0026scaron;nik M, Rauter BH, Bizovičar N. Effects of virtual reality-based treadmill training on 104 the balance and gait ability in patients after stroke: a randomized controlled trial. Hrvat Rev za Rehabil istraživanja [Internet]. 2021 Dec 23 [cited 2022 May 8];57(2):92\u0026ndash;102. Available from: https://www.zebris.\u003c/li\u003e\n\u003cli\u003ePeruzzi A, Zarbo IR, Cereatti A, Della Croce U, Mirelman A. An innovative training program based on virtual reality and treadmill: effects on gait of persons with multiple sclerosis. Disabil Rehabil [Internet]. 2017 Jul 17;39(15):1557\u0026ndash;63. Available from: https://www.tandfonline.com/doi/full/10.1080/09638288.2016.1224935\u003c/li\u003e\n\u003cli\u003eChan A-W, Tetzlaff JM, G\u0026oslash;tzsche PC, Altman DG, Mann H, Berlin J, Dickersin K, Hr\u0026oacute;bjartsson A, Schulz KF, Parulekar WR, Krleža-Jerić K, Laupacis A, Moher D. SPIRIT 2013 Explanation and Elaboration: Guidance for protocols of clinical trials. BMJ. 2013;346:e7586\u003c/li\u003e\n\u003cli\u003eSimis M, Fregni F, Battistella LR. Transcranial direct current stimulation combined with robotic training in incomplete spinal cord injury: a randomized, sham-controlled clinical trial. Spinal Cord Ser Cases. 2021 Sep 27;7(1):87. doi: 10.1038/s41394-021-00448-9. PMID: 34580282; PMCID: PMC8476486.\u003c/li\u003e\n\u003cli\u003eGunduz B, Erhan B. Updates in ASIA examination: Lower extremity motor examination. T\u0026uuml;rkiye Fiziksel Tıp Ve Rehabilitasyon Dergisi [Internet]. 2015 Jul 7;61(1):19\u0026ndash;24. Available from: https://doi.org/10.5152/tftrd.2015.65632\u003c/li\u003e\n\u003cli\u003eLemay, J. F., \u0026amp; Nadeau, S. (2010). Standing balance assessment in ASIA D paraplegic and tetraplegic participants: concurrent validity of the Berg Balance Scale. Spinal cord, 48(3), 245\u0026ndash;250. https://doi.org/10.1038/sc.2009.119\u003c/li\u003e\n\u003cli\u003eWirz, M., M\u0026uuml;ller, R., \u0026amp; Bastiaenen, C. (2010). Falls in persons with spinal cord injury: validity and reliability of the Berg Balance Scale. Neurorehabilitation and neural repair, 24(1), 70\u0026ndash;77. https://doi.org/10.1177/1545968309341059\u003c/li\u003e\n\u003cli\u003eSrisim K, Saengsuwan J, Amatachaya S. Functional assessments for predicting a risk of multiple falls in independent ambulatory patients with spinal cord injury. J Spinal Cord Med. 2015 Jul;38(4):439-45. doi: 10.1179/2045772313Y.0000000186. Epub 2014 Jan 21. PMID: 24621036; PMCID: PMC4612199.\u003c/li\u003e\n\u003cli\u003eDitunno, J. F., Jr, Ditunno, P. L., Scivoletto, G., Patrick, M., Dijkers, M., Barbeau, H., Burns, A. S., Marino, R. J., \u0026amp; Schmidt-Read, M. (2013). The Walking Index for Spinal Cord Injury (WISCI/WISCI II): nature, metric properties, use and misuse. Spinal cord, 51(5), 346\u0026ndash;355. https://doi.org/10.1038/sc.2013.9\u003c/li\u003e\n\u003cli\u003eScivoletto G, Tamburella F, Laurenza L, Foti C, Ditunno JF, Molinari M. Validity and reliability of the 10-m walk test and the 6-min walk test in spinal cord injury patients. Spinal Cord. 2011 Jun;49(6):736-40. doi: 10.1038/sc.2010.180. Epub 2011 Jan 11. PMID: 21221120.\u003c/li\u003e\n\u003cli\u003eItzkovich, M., Gelernter, I., Biering-Sorensen, F., Weeks, C., Laramee, M. T., Craven, B. C., \u0026hellip; Catz, A. (2007). The Spinal Cord Independence Measure (SCIM) version III: Reliability and validity in a multi-center international study. Disability and Rehabilitation, 29(24), 1926\u0026ndash;1933. https://doi.org/10.1080/09638280601046302\u003c/li\u003e\n\u003cli\u003eJang, Y., Hsieh, C. L., Wang, Y. H., \u0026amp; Wu, Y. H. (2004). A validity study of the WHOQOL-BREF assessment in persons with traumatic spinal cord injury. Archives of physical medicine and rehabilitation, 85(11), 1890\u0026ndash;1895. https://doi.org/10.1016/j.apmr.2004.02.032\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"spinal cord injury, neuromodulation, gait rehabilitation, Treadmill training, innovative strategies","lastPublishedDoi":"10.21203/rs.3.rs-6750457/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6750457/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIncomplete complete spinal cord injury (iSCI) leads to significant motor impairments, affecting mobility and quality of life. Emerging rehabilitation strategies, including neuromodulation and virtual reality treadmill training, have shown potential in enhancing motor recovery among individuals with neurological conditions. However, the synergistic effects of their simultaneous application remain underexplored. This study protocol outlines a randomized controlled trial (RCT) to investigate the synergistic effects of transcranial direct current stimulation (tDCS) and virtual reality-assisted treadmill training (VRATT) on motor functions in individuals with iSCI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a single-blind, two-group randomized controlled trial. 52 individuals with incomplete spinal cord injury will be recruited based on inclusion criteria. They will be randomly allocated to transcranial direct current stimulation (active or sham group). Both the groups will simultaneously receive virtual reality-assisted treadmill training. The intervention will be provided for 15 sessions over a span of four weeks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome measure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLower extremity motor score will be used for assessment of muscle strength of lower extremities; balance assessment will be done through Berg balance scale and functional reach test. Kinetic and kinematic parameters of the gait cycle will be analyzed with the Walker View treadmill. Walking ability and walking speed will be determined using the Walking Index for Spinal Cord Injury (version II) and the 10-meter walk test, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial will provide new knowledge about the effectiveness of combined transcranial direct current stimulation with VR-assisted treadmill training on motor functions, functional independence, and quality of life of individuals with SCI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrail Registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical Trials Registry – India, CTRI/2024/11/076226, Registered on 04/11/2024\u003c/p\u003e","manuscriptTitle":"Optimizing Motor Functions in Incomplete Spinal Cord Injury with Simultaneous Application of Transcranial Direct Current Stimulation and Virtual Reality Assisted Treadmill Training: A Study Protocol for a Randomized Controlled Trail","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-21 18:29:56","doi":"10.21203/rs.3.rs-6750457/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2026-02-12T19:07:20+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-07-17T09:19:03+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-17T05:15:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-27T10:04:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"Trials","date":"2025-05-26T07:44:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d5e103e2-d471-436a-a324-6c3efe244079","owner":[],"postedDate":"July 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-17T01:24:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-21 18:29:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6750457","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6750457","identity":"rs-6750457","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}