Neural Plasticity and Motor Recovery After Early and Intensive Upper Extremity Motor Training in People With c-SCI (REPAIR-SCI)

Neural Plasticity and Motor Recovery After Early and Intensive Upper Extremity Motor Training in People With Cervical Spinal Cord Injury

After spinal cord injury (SCI), there is a disruption in neural circuits resulting in paralysis. There is not yet a cure for paralysis. In persons with Cervical SCI (pwC-SCI) recovery of arm-hand function is very important as it has a significant impact on the patients' level of independence and quality of life. Recovery is assumed to involve alterations in both central and peripheral motor systems. Motor training at an intensive dosage potentially provides a powerful stimulus for neurological recovery. This project exploits the peripheral and central neuroplastic effect of an early (<10 weeks after injury) and intensive (10 weeks of 12 hours in addition to usual care) upper limb motor training program (EIUMT) directed at recovery below the level of the injury in pwC-SCI within an international multi-center randomized controlled trial including 40 pwC-SCI. It has 4 objectives: to investigate 1)central neural plasticity by identifying alterations in cortical neuroplasticity and corticospinal excitability; 2)peripheral neural plasticity by identifying alteration in axonal excitability and number of motor units; 3)behavioral motor recovery of upper limb and 4)relationships between dose dimensions of motor intervention and behavioral and neurophysiological outcome measures aer EIUMT. Cutting-edge neurophysiological measures are used to provide insight in the mechanism of neuroplasticity after EIUMT and will be taken before and after EIUMT and at 6 months follow-up.

Study Overview

• Status: Not yet recruiting
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Other: experimental group: intensive motor training; Other: usual care

Detailed Description

Background of the study:

Paralysis or paralysis is the most common effect of spinal cord injury (SCI) on individuals. Paralysis affects the ability to walk, perform self-care, live independently and participate in work and leisure activities. In individuals with cervical spinal cord injury, arm and hand function is very important. The most promising and easily implemented intervention that could promote neurological recovery and make a lasting difference in the lives of people with spinal cord injury is early and intensive motor training aimed at recovery below the injury level. This intervention takes advantage of the early plasticity of the nervous system. By maximizing muscle activation in the first few days after injury, we can target the nervous system's unique capacity for neural plasticity where changes can occur in central and peripheral motor systems.

Objective of the study:

This project aims to investigate peripheral and central neuroplasticity following an early (<10 weeks after injury) and intensive (10weeks of 12 hours of additional therapy) upper extremity motor training program (EIUMT) aimed at recovery below the lesion level.This project has 4 objectives: to investigate 1) central neural plasticity (identify changes in cortical neuroplasticity and corticospinal excitability; 2) peripheral neural plasticity (identify change in axonal excitability and number of motor units); 3) clinical motor recovery of the upper limbs and 4) relationships between dose dimensions of motor intervention and clinical and neurophysiological outcome measures after EIUMT. Advanced neurophysiological measurements and clinical measurements will be taken before and after EIUMT and at 6-month follow-up.

Study design:

a multicenter pragmatic randomised controlled study in 2 countries

Study population:

40 persons with cervical spinal cord injury (20 participants in the control and intervention groups) Inclusion criteria: Individuals are eligible to participate if they have suffered a traumatic or non-traumatic cervical spinal cord injury(with neurological level C4 or below) within the previous 10 weeks, have AIS (ASIA Impairment Scale) A lesion with motor function more than three levels below motor level (on one or both sides) or have AIS C or AIS D lesion (as defined by the International Standards for the Neurological Classification of spinal cord injury), are older than 16 years of age, have received permission to begin rehabilitation and are likely to remain an inpatient for the next 10 weeks.

Exclusion criteria: Participants will be excluded if they have a significant medical or physical condition or psychiatric illness that could prevent the person from participating in the study, or would place the person at unacceptable risk if they were to participate.

Intervention:

The intervention group receives 12 hours of motor training each week. This involves active and targeted motor training of all affected muscles below the injury level in the context of functional activities.

The control group receives only standard rehabilitation and care.

Primary study parameters/outcome of the study:

Central plasticity via: Single pulse TMS (transcranial magnetic stimulation) (cortical mapping and rest motor threshold) 10 weeks after randomisation

Secundary study parameters/outcome of the study:

Clinical Measures: Upper Extremity Motor Score, Spinal Cord Independence Measure (SClM-zelfzorg); Van Lieshout Test (VLT);Grades redefined assessment of strength sensibility and Prehension (GRASSP); Hand-Held Dynamometry; accelerometry (session density: active therapy time/session length); perceived difficulty and exertion) Central plasticity: Paired pulse TMS: (SICI (short interval intracortical inhibition); LICI (long interval intracortical inhibition); SICF (short interval intracortical inhibition); peripheral plasticity: NET (Nerve excitability testing) en MScanFit MUNE(Compound muscle action potential (CMAP).

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Annemie Spooren, Prof. Dr.; Phone Number: 11269332; Email: annemie.spooren@uhasselt.be
• Study Contact Backup: Name: Lisa Tedesco Triccas, Prof. Dr.; Email: lisa.tedescotriccas@uhasselt.be

Study Locations

• Belgium
  • Gent, Belgium
    • UZGent
    • Contact: Kristine Oostra, Prof. Dr.
  • Leuven, Belgium
    • UZLeuven Campus Pellenberg
    • Contact: Koen Peers, Prof. Dr.
• Netherlands
  • Hoensbroek, Netherlands
    • Zorggroep Adelante
    • Contact: Charlotte Van Laake, dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Traumatic or non-traumatic C-SCI below C4 in the preceding 10 weeks; age over 16 years; have an incomplete SCI or an AIS A SCI with zones of partial motor paralysis (as defined by the International Standards for the Neurological Classification of SCI (ISNCI) and medically stable.

Exclusion Criteria:

• SCI with ASIA Impairment Scale (AIS) A without zones of partial preservation (decided based on former studies [58]) and expertise of the team; SCI with any significant medical condition that could prevent the person from participating. In order to ensure TMS measurement can be performed, patients will only be included for this measure if they have a positive response to motor evoked potential measurement (MEP+) [59] and will be excluded in the presence of contraindications for TMS application such as epilepsy, metal implants in the brain,defibrillator, pacemaker and pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intensive upper limb training; The intervention group receives 12 hours of motor training each week upon usual care during 10 weeks. This involves active and targeted motor training of all affected muscles below the injury level in the context of functional activities.	Other: experimental group: intensive motor training; Intervention group: receive an extra 12 hours of motor training each week (distributed over the week) for 10 weeks. It will involve active and targeted motor training of all affected muscles of the upper limb below the level of the injury within the context of practice of functional activities. Interventions will be goal directed and individualized to the needs of each participant with a focus on training that addresses each person's specific motor problem, promoting motor learning as well as stimulating neural plasticity. All patients will continue to receive usual physiotherapy and usual rehabilitation.
Other: usual care; The control group receives only standard rehabilitation and care	Other: usual care; usual rehabilitation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in single pulse TMS: mapping	to evaluate changes in cortical reorganisation	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
changes in single pulse TMS: resting motor threshold	to asses changes in cortical reactivity	before intervention; at 10 weeks (after intervention) and at 6 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes SICI	to evaluatie changes in Short interval intracortical inhibition	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
changes SICF	short-interval intracortical facilitation	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
changes in LICI	long-interval intracortical inhibition	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
changes in MscanFit MUNE	Compound muscle action potential (CMAP) scans will be recorded	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
changes in NET (Nerve excitability testing)	Strength duration time constant (SDTC), threshold electrotonus (TE), I/V relationship (I/V) and recovery cycles (RC) will be measured.	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
changes in behavioral measures: Upper extremity motor score	score on 50	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
changes in Spinal Cord independence Measures	questionaire: self-care score	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
changes in Van Lieshout Test	basis upper extremity skills	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
changes in GRASSP	Grades redefined assessment of strength sensibility and Prehension	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
changes in hand held dynamometry	strength in hand	before intervention; at 10 weeks (after intervention) and at 6 months follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
therapy difficulty	VAS	before session; after completion of session an average of 60 minutes
session density	accelerometry	start intervention up to 10 weeks
therapy perceived exertion	VAS	before session; after completion of session an average of 60 minutes

Collaborators and Investigators

• Sponsor: Annemie Spooren
• Collaborators: Universitaire Ziekenhuizen KU Leuven; University of Aarhus; University Hospital, Ghent; University of Sydney; Research Foundation Flanders; Adelante, Centre of Expertise in Rehabilitation and Audiology
• Investigators: Principal Investigator: Annemie Spooren, Prof. Dr., Hasselt University

Study record dates

Study Major Dates

• Study Start (Estimated): October 5, 2023
• Primary Completion (Estimated): August 28, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: June 14, 2023
• First Submitted That Met QC Criteria: October 2, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: motor recovery; neural plasticity; spinal cord rehabilitation; therapy dose; upper limb training
• 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: REPAIR-SCI_UH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

pseudomised data will be shared with the Aarhys university because they will assist in data-analyses.

the protocol will be shared with the partners (Aarhus University, Sydney University, UZGent, UZLeuven and Adelante Zorggroep)

• IPD Sharing Time Frame: during and after datagathering
• IPD Sharing Access Criteria: only for collaborating partners
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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