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

Central and Peripheral Neuroplasticity in Cervical Spinal Cord Injury Following Intensive Upper Limb Motor Training

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 (<13 weeks after injury) and intensive (8 weeks of 6 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 44 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 alterations 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 after 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: Recruiting
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Other: usual care; Other: experimental group: intensive motor training

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 injuries 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 weeks 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 (<13 weeks after injury) and intensive (8 weeks of 6 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:

44 persons with cervical spinal cord injury (22 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 within the previous 13 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 8 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 6 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 (Baseline vs 8 weeks after randomisation):

Central plasticity via: Single pulse TMS (transcranial magnetic stimulation) (Resting Motor Threshold) Peripheral plasticity via: Peripheral nerve assessment (Compound muscle action potential (CMAP)) Functional recovery via: Grades redefined assessment of strength, sensibility and Prehension (GRASSP)

Secondary study parameters/outcome of the study:

Clinical Measures: Upper Extremity Motor Score, Spinal Cord Independence Measure (SClM-selfcare); Van Lieshout Test (VLT); Hand-Held Dynamometry; accelerometry (session density: active therapy time/session length); perceived difficulty and exertion) Central plasticity: Single Pulse TMS: Stimulus-Response Function, Cortical mapping, Paired pulse TMS: SICI (short interval intracortical inhibition); LICI (long interval intracortical inhibition) Peripheral plasticity: NET (Nerve excitability testing) and MScanFit MUNE.

• Study Type: Interventional
• Enrollment (Estimated): 44
• 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
  • Antwerp, Belgium, 2650
    • Recruiting
    • Revalidatieziekenhuis RevArte
    • Contact: Nathalie Vaes; Phone Number: +32 3 210 60 95; Email: nathalie.vaes@revarte.be
  • Ghent, Belgium
    • Recruiting
    • UZGent
    • Contact: Kristine Oostra, Prof. Dr.
  • Leuven, Belgium
    • Not yet recruiting
    • UZLeuven Campus Pellenberg
    • Contact: Koen Peers, Prof. Dr.
• Netherlands
  • Hoensbroek, Netherlands
    • Recruiting
    • 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 in the preceding 13 weeks; age over 16 years; have an incomplete SCI categorized as AIS C or D 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) and expertise of the team; SCI with any significant medical condition that could prevent the person from participating. Patients will be excluded from the measures of central plasticity 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
Other: usual care; The control group receives only standard rehabilitation and care	Other: usual care; usual rehabilitation
Experimental: intensive upper limb training; The intervention group receives 6 hours of motor training each week upon usual care during 8 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 6 hours of motor training each week (distributed over the week) for 8 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in single pulse TMS: resting motor threshold	to asses changes in cortical reactivity	- before intervention; at 4 weeks (inbetween measure), at 8 weeks (after intervention) and at 6 months follow-up
changes in GRASSP	Grades redefined assessment of strength sensibility and Prehension	- before intervention; at 8 weeks (after intervention) and at 6 months follow-up
Changes in Compound Muscle Action Potential (CMAP)	Changes in amplitude of CMAP	- before intervention; at 4 weeks (inbetween measure), at 8 weeks (after intervention) and at 6 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in single pulse TMS: mapping	to evaluate changes in cortical reorganisation	- before intervention; at 8 weeks (after intervention) and at 6 months follow-up
Single-pulse TMS: Stimulus Response Curve	- to assess cortical excitability	- before intervention; at 4 weeks (inbetween measure), at 8 weeks (after intervention) and at 6 months follow-up
changes SICI	to evaluatie changes in Short interval intracortical inhibition	- before intervention; at 8 weeks (after intervention) and at 6 months follow-up
changes in LICI	long-interval intracortical inhibition	- before intervention; at 8 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 4 weeks (inbetween measure), at 8 weeks (after intervention) and at 6 months follow-up
changes in NET (Nerve excitability testing)	Stimulus-Response Curve, Strength duration time constant (SDTC), threshold electrotonus (TE), I/V relationship (I/V) and recovery cycles (RC) will be measured.	- before intervention; at 4 weeks (inbetween measure), at 8 weeks (after intervention) and at 6 months follow-up
changes in behavioral measures: Upper extremity motor score	score on 50	- before intervention; at 8 weeks (after intervention) and at 6 months follow-up
changes in Spinal Cord independence Measures	questionaire: self-care score	- before intervention; at 8 weeks (after intervention) and at 6 months follow-up
changes in Van Lieshout Test	basis upper extremity skills	- before intervention; at 8 weeks (after intervention) and at 6 months follow-up
changes in hand held dynamometry	strength in hand	- before intervention; at 8 weeks (after intervention) and at 6 months follow-up
Goal satisfaction	Subjective scoring 0-10 of four goals	- before intervention; at 8 weeks (after intervention) and at 6 months follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjectively perceived session difficulty	VAS	measurement of one week during the 2., 5. and 8. week of intervention duration; before and after completion of session
Objective active time	accelerometry	- measurement of one week during the 2., 5. and 8. week of intervention duration
Subjectively perceived session intensity	VAS (perceived exertion)	measurement of one week during the 2., 5. and 8. week of intervention duration; before and after completion of session
Therapy documentation	Total session length and UL training session length based on therapy documentation	whole trial period of 8 weeks

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; Rehabilitation Hospital RevArte
• Investigators: Principal Investigator: Annemie Spooren, Prof. Dr., Hasselt University

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2024
• Primary Completion (Estimated): March 28, 2027
• Study Completion (Estimated): August 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): December 12, 2025
• Last Update Submitted That Met QC Criteria: December 5, 2025
• Last Verified: December 1, 2025

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 discussed with Aarhus University because they will assist in data analyses.

The protocol will be shared with the partners (Aarhus University, Sydney University, UZ Gent, UZ Leuven, RZ RevArte, and Adelante Zorggroep)

• IPD Sharing Time Frame: during and after data gathering
• 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
• product manufactured in and exported from the U.S.: No