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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Spinal Cord Trauma

• Study Type: Observational
• Enrollment (Anticipated): 81

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • BG Hospital Unfallkrankenhaus Berlin, Treatment Centre for Spinal Cord Injuries
    • Contact: Thomas Liebscher, MD
• Italy
  • Rome, Italy
    • Center for Neurorehabilitation, Santa Lucia Foundation
    • Contact: Marcella Masciullo, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants from primary care clinics

Description

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).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Complete SCI, AIS A; Patients with complete spinal cord injury (AIS A)
Incomplete SCI, AIS B, C, D; Patients with incomplete spinal cord injury (AIS B, C, D)
Vertebral injuries without SCI; Patients with vertebral injuries without spinal cord injury (control)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Marcel Kopp, MD
• Collaborators: King's College London; Medical University of Vienna; University of Zurich; McGill University Health Centre/Research Institute of the McGill University Health Centre; Ohio State University; Ruhr University of Bochum; University Hospital Tuebingen; Balgrist University Hospital; I.R.C.C.S. Fondazione Santa Lucia; Swiss Federal Institute of Technology; Foundation Wings For Life; Unfallkrankenhaus Berlin

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 1, 2023
• Primary Completion (ANTICIPATED): October 1, 2025
• Study Completion (ANTICIPATED): April 1, 2026

Study Registration Dates

• First Submitted: December 20, 2019
• First Submitted That Met QC Criteria: December 23, 2019
• First Posted (ACTUAL): December 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries
• Other Study ID Numbers: SCIentinel-prolong

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No