Deficit-specific Training in Spinal Disorders

Study Overview
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Brief Summary
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Impairments of walking function after spinal cord lesion due to, for example, inflammation, ischemia or trauma are exceptionally diverse. Depending on the size, location and completeness of the spinal cord lesion, gait dysfunction is often multifactorial, arising from weakness of leg muscles, sensory impairments or spasticity. Locomotor function in humans with spinal cord damage can be improved through training. However, there are no evidence-based guidelines for the treatment of gait dysfunctions and no excepted standards of gait training in this large and heterogeneous group of patients. A lack of evidence-based guidance and standardisation prevents the development of optimal training programs for patients with spinal cord damage and rather broad and subjective clinical judgement is applied to determine patient care. Objective and quantitative techniques like three-dimensional (3D) full-body movement analysis capable of identifying the most relevant determinants of gait dysfunction at the single-patient-level are not yet implemented as diagnostic tool to guide physical therapy in this heterogeneous group of patients. The objective of this project is to further advance current clinical locomotor training strategies by applying a deficit-oriented gait training approach based on subject-specific, objective gait profiles gleaned from 3D gait analysis in chronic, mildly to moderately gait-impaired individuals with spinal cord damage due to inflammation (in multiple sclerosis, MS) or with traumatic or ischemic spinal cord injury (SCI; motor incomplete). Within a parallel-group clinical trial, gait impaired subjects will be characterized by detailed kinematic 3D gait analysis and either trained according to their individual deficits or treated with non-specific, standard walking therapy for six weeks. It is hypothesized that individually adapted, deficit-oriented training is superior in improving walking function than purely task-related, ambulatory training in patients with spinal cord damage. This project may pave the way to more efficient training approaches in subjects with spinal cord damage by transferring and implementing modern gait assessment techniques into clinical neurorehabilitation and to move towards individual, patient-tailored locomotor training programs.

Official Title
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Precision Medicine in the Rehabilitation of Locomotor Function: Individual Gait Profiles for Deficit-specific Training Strategies in Spinal Disorders

Conditions
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Spinal Cord Injuries, Multiple Sclerosis, Gait Disorders, Neurologic, Training, Neurorehabilitation

Intervention / Treatment
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* Behavioral: Gait training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years Diagnosis of chronic spinal cord injury (>6 months cervical or thoracic motor incomplete traumatic or non-traumatic (AIS C, D) above T12 or diagnosis of either primary- progressive, secondary-progressive, or relapsing-remitting multiple sclerosis as defined by the revised McDonald criteria for at least 3 months and with at least one spinal cord lesion as verified in clinical MRI images Able to walk without assistance or devices on the treadmill and 10m over ground, but must have impaired walking function as demonstrated by neurological examination. Exclusion Criteria: Women who are pregnant or breast feeding Current orthopaedic problems of lower limbs History of major cardiac condition (e.g., infarction, insufficiency (NYHA II-IV)) History of major pulmonary condition (e.g., chronic obstructive pulmonary disease GOLD II-IV) Current major depression or psychosis MS exacerbation within 3 months prior to the screening or at any time during the screening period Participation in another training study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Deficit-oriented training group<br> | Behavioral: Gait training<br>* All participants will receive training three times a week for 6 weeks (18 training sessions) at the University Hospital Balgrist, Spinal Cord Injury Centre. Each exercise session will last for 1 hour and will be conducted and supervised by an experienced physical therapist.<br>|
| Active Comparator: Non-specific, standardised walking training group<br> | Behavioral: Gait training<br>* All participants will receive training three times a week for 6 weeks (18 training sessions) at the University Hospital Balgrist, Spinal Cord Injury Centre. Each exercise session will last for 1 hour and will be conducted and supervised by an experienced physical therapist.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six minute walk test (6MWT) |  | Change from screening at 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MS-patients: Expanded disability status scale (EDSS) | neurological score, range from 0 to 10, lower values better than higher values | Change from screening at 10 weeks | 
| SCI-patients: ISNCSCI by the American Spinal Injury Association (ASIA protocol) | Perceptions of light touch (LT) and pinprick (PP) stimuli are scored as 0 for absent, 1 for impaired and 2 for normal (range for sum score for pin prick and light touch: 0-112). Motor function is scored on the Medical Research Council Scale of 0 for total paralysis to 5 for normal strength. Ten muscles are tested bilaterally and individual muscle scores are added together, yielding an ASIA motor score that ranges from 0 to 100. For all assessments higher scores are better than lower scores. | Change from screening at 10 weeks | 
| SCI-patients: Walking index for Spinal Cord Injury (WISCI II) | Range from 0-20, higher values are better than lower values. | Change from screening at 10 weeks | 
| MS-/ SCI-patients: Six-minute walk test (6MWT) |  | 10 weeks | 
| MS-patients. Timed 25-foot walk (T25FW) |  | Change from screening at 10 weeks | 
| SCI-patients: Timed 10-meter walk test (10MWT) |  | Change from screening at 10 weeks | 
| MS-/ SCI-patients: Timed up and go test (TUG) |  | Change from screening at 10 weeks | 
| MS-/ SCI-patients: Kinematic measures on treadmill | A set of key kinematic parameters will be quantified describing leg, trunk and arm movements during walking on a treadmill including range of motion (in degrees) of hip, knee and ankle joints. | Change from screening at 6 and 10 weeks | 
| MS-/ SCI-patients: Kinetic measures | A set of key kinetic parameters will be quantified describing forces of weight loading for both feet using pedobarography. | Change from screening at 6 and 10 weeks | 
| MS-/ SCI-patients: Electromyographic measures | EMG measures include timing of leg muscle activity during walking on treadmill. | Change from screening at 6 and 10 weeks | 
| MS-/ SCI-patients: 12-item WS for walking function (questionnaire) | Questionnaire, range from 12-60 points, lower values are better than higher values. | Change from baseline at 10 weeks | 
| MS-/ SCI-patients: Time to swim 10m |  | Change from baseline at 6 weeks | 
| MS-/ SCI-patients: Kinematic parameters of leg movements during swimming (activity sensors) | A set of key kinematic parameters will be quantified describing leg movements during swimming including range of motion (in degrees) of hip, knee and ankle joints. | Change from baseline at 6 weeks | 
| MS-/SCI-patients: Spinal Cord Independence Measure (SCIM-III) |  | Change from screening at 10 weeks | 
| MS-/ SCI-patients: Magnetic resonance imaging (MRI) |  | Change from baseline at 10 weeks | 
| MS-/ SCI-patients: Magnetic resonance spectroscopy (MRS) |  | Change from baseline at 10 weeks | 
| MS-/ SCI-patients: over ground gait kinematics during clinical walking tests (activity sensors) |  | Change from baseline at 10 weeks |