Autoimmunity And Immune Deficiency After Spinal Cord Injury: Association With Rehabilitation Outcomes

Study Overview
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Brief Summary
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The SCIentinel-prolong study systematically analyzes humoral autoantibody responses and thier interaction with post-spinal cord injury (SCI) immune-deficiency and infections as well as their association with the clinical course of rehabilitation. Therefore, molecular and immunological tests in blood and cerebrospinal fluid specimen are combined with clinical outcomes ranging from neurological function, neuropathic pain and spasticity to walking tests and measures of independence in daily living within the first year after SCI. Including a control group with participants suffering from vertebral fractures without SCI allows to differentiate between neurological and general injury and treatment effects.

Official Title
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Maladaptive Systemic Immune Response After Spinal Cord Injury: Humoral Post-traumatic Autoimmunity Against Central and Peripheral Nervous System Antigens in Association With Neurogenous Immune Depression as a Confounder of Rehabilitation

Conditions
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Spinal Cord Trauma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute traumatic SCI, American Spinal Injury Association Impairment Scale (AIS) A to D, neurologic level of injury C3 - L2 or acute vertebral fracture without SCI Inclusion within 21 days post-injury For Italian centers only: SCI-Treatment using Methylprednisolone (according to NASCIS). Exclusion Criteria: Non-traumatic SCI Severe multiple trauma Serious traumatic brain injury Pre-exiting neurological diseases Malignant Neoplasia, except in complete remission for 5 years Rheumatic diseases / collagenosis / vasculitis Other autoimmune diseases Pre-existing chronic infection Severe alcohol or drug addiction Pregnancy or lactation Simultaneous participation in interventional clinical trials For centers in Germany or Switzerland only: SCI-treatment using Methylprednisolone (according to NASCIS).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Complete SCI, AIS A<br>Patients with complete spinal cord injury (AIS A) | |
| Incomplete SCI, AIS B, C, D<br>Patients with incomplete spinal cord injury (AIS B, C, D) | |
| Vertebral injuries without SCI<br>Patients with vertebral injuries without spinal cord injury (control) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-traumatic autoimmunity | Prevalence of autoantibodies against central and peripheral nervous system antigens in cerebrospinal fluid and serum | 3 months (10-14 weeks) post injury | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Standards for Neurological Classification of SCI - Upper Extremity Motor Score | Minimum 0, maximum 50; higher scores mean a better outcome | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| International Standards for Neurological Classification of SCI - Lower Extremity Motor Score | Minimum 0, maximum 50; higher scores mean a better outcome | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| International Standards for Neurological Classification of SCI - Sensory light touch score | Minimum 0, maximum 112; higher scores mean a better outcome | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| International Standards for Neurological Classification of SCI - Sensory pin prick score | Minimum 0, maximum 112; higher scores mean a better outcome | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| American Spinal Injury Association Impairment Scale | Ordinal alphabetical scale. Range A to E. Change in the scale to one of the subsequent letters in the alphabet means a better outcome. | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| Spinal Cord Independence Measure III | Composite instrument for the assessment of physical independence; minimum 0, maximum 100; higher scores mean a better outcome | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| Walking Index for Spinal Cord Injury II | Score for walking ability; minimum 0, maximum 20; higher scores mean a better outcome | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| 10m-walk-test | Time in seconds required for 10 meter walking; higher scores mean a worse outcome | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| Timed-up-and go | Time in seconds needed to raise from a chair, walk a distance of 3 m, turn back and sit down again; higher scores mean a worse outcome | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| 6-minutes-walk-test | Walking distance in meters covered in 6 minutes; higher scores mean a better outcome | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| Neuropathic Pain Scale 10 | Instrument comprising 10 numeric analogue scales for intensity and qualities of pain; each item ranges from 0-10; higher scores mean a worse outcome | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| Spinal Cord Injury Pain Basic Dataset | Composite instrument for the assessment of pain locations, type and intensity | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| Modified Ashworth Scale | Assessment of muscle tone and resistance to passive motion; minimum 0, maximum 4, higher scores mean a worse outcome | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| Penn spasm frequency scale | Patient rated frequency of spasms; minimum 0, maximum 4; higher scores mean a worse outcome | 2 weeks, 3-6 weeks, 3 month, 6month, 1 year post injury | 
| Somatosensory evoked potentials | Tibial nerve and ulnar nerve; response is graded as ranging from 1=abolished to 4=normal response; higher scores mean better outcome | 2 weeks, 3 months | 
| Motor evoked potentials | Anterior tibial muscle, abductor hallucis, abductor digiti minimi; response is graded as ranging from 1=abolished to 4=normal response; higher scores mean better outcome | 2 weeks, 3 months | 
| Electroneurography | Abductor hallucis and abductor digiti minimi; latency, amplitude and F-waves | 2 weeks, 3 months | 
| Sympathetic skin response | Skin response at palm and sole | 2 weeks, 3 months | 
| Human Leukocyte Antigen - DR isotype expression on monocytes | Anti-Human Leukocyte Antigen - DR isotype antibodies bound per monocyte, higher values mean better outcome | 1 day, 3 days, 1week, 2 weeks, 3-6 weeks, 3 months, 6 months, 1 year post injury | 
| Immune phenotyping | Panel of T-lymphocyte and B-lymphocyte subpopulations | 1 day, 3 days, 1week, 2 weeks, 3-6 weeks, 3 months, 6 months, 1 year post injury | 
| Functional immune assays | White blood cell ex-vivo stimulation | 1 day, 3 days, 1week, 2 weeks, 3-6 weeks, 3 months, 6 months, 1 year post injury | 
| Damage Associated Molecular Patterns | Immunoassays in plasma and CSF | 1week, 3 months, | 
| Markers of Ferroptosis | Immunoassays in plasma and CSF | 1week, 3 months |