Background and Rationale:

Traumatic spinal cord injury (SCI) affects approximately 12,400 individuals annually in the USA, predominantly impacting healthy young adults aged 20-40 years. Complete SCI above the lumbar region results in paraplegia or tetraplegia, severely compromising quality of life. Wheelchair-dependent lifestyle and immobilization lead to serious secondary complications including osteoporosis, diabetes mellitus, atherosclerosis, pressure ulcers, depression, and pathological fractures. Robotic exoskeletons have emerged as promising rehabilitation tools since the 2000s, enabling independent walking and stair climbing beyond wheelchair use.

Study Objectives:

This clinical trial investigates the role of ReWalk lower-limb human exoskeleton in rehabilitation by:

Integrating exoskeleton-assisted gait training into rehabilitation protocols and comparing functional and physiological outcomes with conventional conservative treatment in SCI-induced paralysis Examining gastrointestinal and urogenital changes Assessing general well-being and patient compliance

Methods:

This prospective, controlled study enrolls patients with lower limb paralysis following SCI for minimum 6-month rehabilitation. The control group receives traditional physiotherapy and physical rehabilitation only. All procedures comply with Good Clinical Practice principles and applicable regulations.

Inclusion criteria (FDA-approved): Complete SCI below T4 with paraparesis/paraplegia; ≥4 months post-injury; adequate arm/shoulder strength for crutch use; appropriate bone density (hip t-score >-3.5); intact skeletal system with stable spine; ability to stand safely; good general health; height 160-190cm; weight ≤100kg; adequate lower limb range of motion.

Exclusion criteria: Severe neurological diseases beyond SCI; significant concurrent illnesses; severe spasticity (Modified Ashworth 4); unstable spine or limbs; heterotopic ossification; significant contractures; psychiatric/cognitive impairment; pregnancy.

Training Protocol:

The rehabilitation program consists of five phases:

Paravertebral and back muscle strengthening (weeks 1-4): Core strengthening exercises focusing on sitting balance, assessed weekly via trunk control measurement scale Standing, sitting, and device donning (weeks 5-6): Learning independent device application and safe standing balance Gait training (weeks 7-8): Mastering independent device control through various stepping patterns Stair training (weeks 9+): Learning stair negotiation after passing final skill test Follow-up phase (6+ months): Maintenance therapy at reduced frequency (3x/week)

Assessment Parameters:

Baseline assessments include: ASIA Impairment Scale, bone densitometry, Modified Ashworth Scale, Barthel Index, Functional Independence Measure (FIM), VAS pain/fatigue scales, SF-36, Beck's anxiety/depression inventories.

Progress evaluations at major milestones include functional tests (10-meter walk, Timed Up-and-Go, Berg Balance, Spinal Cord Independence Measure) and ReWalk skill assessments.

Follow-up assessments (6-month minimum) repeat baseline measures focusing on bone density, functional independence, quality of life, and mental health.

Expected Outcomes:

Improved bone density with exoskeleton training compared to conventional treatment Improved general well-being and better patient compliance This study aims to confirm previous international findings demonstrating superior outcomes with robotic rehabilitation technology regarding spasticity reduction, bone density preservation, body composition improvement, and gastrointestinal/urogenital/mental health enhancement compared to traditional treatment approaches.

Background and rationale Traumatic spinal cord injury (SCI) has major epidemiological and societal impact. Incidence is approximately 12,400 new cases/year in the USA, with a proportionally similar rate expected in Hungary. SCI most often results from traffic-related injuries and typically affects young, previously healthy adults (20-40 years). Depending on neurological level and severity, SCI may cause paraparesis/paraplegia or tetraparesis/tetraplegia, leading to profound functional limitations and reduced quality of life.

For individuals with complete SCI above the lumbar region, independent standing and walking are generally not achievable with current standard care. Long-term wheelchair use and immobilization contribute to common secondary complications, including osteoporosis, diabetes mellitus, atherosclerosis, pressure ulcers, depression, and pathological fractures. Therefore, a central goal of rehabilitation after complete SCI is to prevent or minimize immobilization-related complications and to support the highest possible level of independence and quality of life.

Robotic lower-limb exoskeletons have been introduced into rehabilitation since the 2000s. These externally worn robotic frames can enable upright standing, walking, and potentially stair negotiation, supplementing wheelchair mobility. Prior clinical studies indicate that the ReWalk exoskeleton is feasible and safe for supervised clinical rehabilitation and, in selected users, for home/community use. Exoskeleton-assisted gait produces measurable cardiorespiratory demands and may replicate some beneficial physiological effects of able-bodied walking. Published data suggest possible improvements in functional walking capacity compared with some conventional gait-assist approaches (e.g., dynamic gait orthoses), and potential benefits in spasticity, as well as urogenital and gastrointestinal function, patient acceptance, sleep, well-being, and depressive symptoms.

Based on these findings, the present study is designed to compare outcomes of ReWalk-based robotic gait rehabilitation with outcomes achieved by conventional physiotherapy/fiziotherapy in a similar SCI population, with special attention to domains where exoskeleton-assisted upright mobility may provide added value (e.g., spasticity, bone density, body composition, autonomic functions, and mental health).

Objectives

Primary objective:

To integrate exoskeleton-assisted gait training into the rehabilitation process and compare changes in selected functional and physiological parameters with those achieved through traditional conservative rehabilitation in patients with paralysis due to SCI.

Secondary objectives:

To study gastrointestinal and urogenital changes during and after exoskeleton-based rehabilitation.

To assess general well-being, patient satisfaction, and compliance/adherence. 3. Study design and setting Design: Prospective, controlled clinical study. Duration: Minimum 6 months per participant (training plus follow-up).

Groups:

Intervention group: ReWalk exoskeleton-assisted rehabilitation in addition to standard rehabilitation elements.

Control group: Patients from the same source population meeting the same eligibility criteria but receiving conventional physiotherapy/fiziotherapy only (no exoskeleton training).

Regulatory/quality framework: Conducted in accordance with applicable laws, current professional recommendations, and Good Clinical Practice (GCP) principles.

Ethics: Participation requires ethical approval and written informed consent. 4. Participant selection 4.1 Inclusion criteria (FDA-based)

Participants must meet all of the following:

Complete SCI below T4 with paraparesis/paraplegia. At least 4 months since the SCI event. Adequate upper-limb and shoulder strength to use forearm crutches. Adequate bone density, supported by DXA when required: hip T-score greater than -3.5.

Intact skeletal system: in addition to a stable or stabilized spine, there is no fresh, non-consolidated fracture that could affect device use or walking.

Ability to stand confidently using a standing aid such as EasyStand (or similar).

Good general health.

Anthropometrics compatible with the device:

Height 160-190 cm Femur length 43.5-56 cm Tibia length 36-48.5 cm Body weight maximum 100 kg.

Adequate lower-limb range of motion:

Physiological ankle position Hip extension to 0° Knee contracture less than 10° 4.2 Exclusion criteria (FDA-based)

Any of the following will exclude participation:

Severe neurological disease other than traumatic SCI (e.g., multiple sclerosis, cerebral palsy, ALS, traumatic brain injury).

Severe comorbidities that limit safe training (e.g., active infection, significant cardiovascular disorder affecting load tolerance, pulmonary disease).

Abdominal or thoracic conditions that prevent safe exoskeleton use (e.g., enterostoma, chest deformity), or pressure ulcers that interfere with device wearing.

Severe spasticity (Modified Ashworth Scale score 4). Unstable spine or lower-limb/pelvic conditions limiting load-bearing (e.g., non-healed fracture, post-amputation state).

Heterotopic ossification that restricts joint mobility beyond allowed limits.

Significant contractures:

Plantar flexion contracture greater than 0° Knee contracture greater than 10° Hip flexion contracture 20° Psychiatric or cognitive impairment that limits safe device handling or study participation.

Pregnancy. 5. Intervention and rehabilitation protocol 5.1 Safety and supervision Participants are under continuous medical supervision during treatment. Exoskeleton training is taught and delivered by trained movement therapists. Until independent walking with the device is achieved, at least two physiotherapists ensure safe use.

In early phases, sessions occur 5 times per week, 60-90 minutes per session. After a participant acquires safe independent use, training continues and follow-up assessments proceed for at least 6 months. For long-term maintenance, session frequency may be reduced (see follow-up phase).

A multidisciplinary team supports assessment and management of outcomes, including an internist, a urologist experienced in urodynamic testing, a dietitian, and a clinical psychologist, as required for physiological and mental-health endpoints.

5.2 Stepwise training phases Phase 1: Preparatory physiotherapy-trunk and upper-limb strengthening

To safely control the robotic device, specific motor capacities are required. A multi-week preparatory program is conducted, focusing on:

Improving sitting balance, essential for safe device use. Strengthening abdominal and paravertebral muscles (performed in supine, prone, quadruped, and especially seated positions).

Training dynamic trunk balance (with or without supportive tools). Strengthening upper limbs due to increased load from crutch-assisted walking during exoskeleton use.

Progress is assessed weekly using the Trunk Control Measurement Scale. If the participant reaches 15/58 points, the program proceeds to the next phase.

Phase 2: Donning/doffing, sit-to-stand and stand-to-sit, standing balance

Participants learn:

Independent donning of the device. Safe standing up and sitting down techniques.

Standing balance and weight shifting tasks, including:

Standing with one crutch (as appropriate) Maneuvering and turning tasks Trunk control and balance are assessed repeatedly using the Trunk Control Measurement Scale and the Berg Balance Scale. Advancement requires safe, independent task execution, stable frontal-plane weight shifting, and the ability to safely lift and reposition crutches.

Phase 3: Gait acquisition

Participants learn independent device operation using manufacturer/FDA-defined step settings. Progress is evaluated with:

Intermediate Skill Test every 2 weeks 10-Meter Walk Test every 2 weeks Timed Up and Go (TUG) every 2 weeks After 8 weeks, if the participant can control and use the device safely, the Final Skill Test is performed.

Phase 4: Stair training If Final Skill Test competencies are met, stair negotiation skills are introduced as the final step of training.

Phase 5: Follow-up/maintenance phase For participants capable of independent use, therapy frequency may be reduced to three sessions per week as maintenance therapy, while follow-up measurements continue per schedule.

6. Outcome measures and assessments 6.1 Ongoing safety monitoring

At each session:

Vital signs are measured and documented (blood pressure, heart rate). Skin is inspected for irritation/pressure injury before and after device use.

If skin irritation or injury occurs:

Lesion extent is monitored (diameter, longitudinal and transverse dimensions), with special focus on depth.

Photo documentation is performed. Findings are categorized according to National Pressure Ulcer Advisory Panel (NPUAP) recommendations.

If injury occurs at a device contact point, or if skin/soft tissue/bone injury is suspected, device use must be suspended.

All relevant events and observations are recorded; documentation includes images and video as applicable.

6.2 Baseline assessments (at enrollment) ASIA Impairment Scale (AIS) and Frankel scale Bone densitometry (DXA) Body composition measurement Spasticity: Modified Ashworth Scale (mAS) Barthel Index Functional Independence Measure (FIM) Pain and fatigue: Visual Analog Scale (VAS) Quality of life: SF-36 Mental health: Beck Anxiety Inventory and Beck Depression Inventory (as specified) ReWalk medical clearance form Lower-limb circumference measurement 6.3 Assessments at major milestones (minimum at acquisition of new skills / next training level) Barthel Index FIM VAS pain/fatigue Trunk Control Measurement Scale Modified Ashworth Scale (mAS) 10-Meter Walk Test Timed Up and Go (TUG) Spinal Cord Independence Measure (SCIM) Berg Balance Scale ReWalk skill tests (as scheduled) 6.4 Follow-up phase assessments Bone densitometry (DXA) FIM Modified Ashworth Scale (mAS) SCIM SF-36 Beck anxiety and depression questionnaires Compliance and satisfaction assessed using a 5-point Likert scale 7. Expected outcomes

Compared with conventional rehabilitation alone, ReWalk exoskeleton-assisted gait rehabilitation is expected to be associated with:

Improved body composition and improved or preserved bone density, reflecting benefits of upright, load-bearing, and increased physical activity.

Improved general well-being, patient satisfaction, and treatment adherence/compliance.

8. Summary This prospective, controlled clinical study evaluates the added value of integrating ReWalk exoskeleton-assisted gait training into SCI rehabilitation. By comparing a ReWalk intervention group with a matched control group receiving conventional therapy only, the study aims to quantify functional, physiological, autonomic, and psychosocial effects of robotic upright mobility, while maintaining rigorous safety monitoring and standardized outcome assessments over a minimum 6-month period.

Inclusion Criteria:

• Complete spinal cord injury below thoracic vertebra level 4 with paraparesis or paraplegia
• At least 4 months since the spinal cord injury
• Adequate arm and shoulder muscle condition to use forearm crutches
• Adequate bone density; if needed confirmed by dual energy X ray absorptiometry: hip T score greater than minus 3.5
• Intact skeletal system; stable or stabilized spinal injury, with no fresh, non consolidated fracture that would affect device use or walking
• Able to stand confidently using a standing device similar to EasyStand
• Good general health
• Body dimensions compatible with the device: height 160 to 190 centimeters; femur length 43.5 to 56 centimeters; tibia length 36 to 48.5 centimeters
• Body weight maximum 100 kilograms
• Adequate lower limb range of motion: physiological ankle position; hip extension 0 degrees; knee contracture less than 10 degrees

Exclusion Criteria:

• History of severe neurological disease other than traumatic spinal cord injury (for example multiple sclerosis, cerebral palsy, amyotrophic lateral sclerosis, traumatic brain injury)
• Serious active illness (for example infection) or reduced exercise tolerance due to cardiovascular or pulmonary disease
• Abdominal or thoracic condition that prevents exoskeleton use (for example enterostoma, chest deformity) or pressure ulcer that interferes with fitting or use
• Severe spasticity (Modified Ashworth Scale grade 4)
• Unstable spine, or limb/pelvic condition limiting load bearing (for example non healed fracture, post amputation state)
• Heterotopic ossification that impairs joint mobility beyond allowed limits
• Significant contractures: ankle plantar flexion contracture greater than 0 degrees; knee contracture greater than 10 degrees; hip flexion contracture 20 degrees
• Psychiatric or cognitive impairment that limits safe device handling or study participation
• Pregnancy