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

Spinal Cord Injuries Clinical Trial

— REPAIR-SCI  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06065384
• Other study ID #: REPAIR-SCI_UH
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 5, 2023
• Est. completion date: February 28, 2027

Study information

• Verified date: October 2023
• Source: Hasselt University
• Contact: Annemie Spooren, Prof. Dr.
• Phone: 11269332
• Email: annemie.spooren[@]uhasselt.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: February 28, 2027
• Est. primary completion date: August 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Spinal Cord Injuries

Intervention

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.
• usual care
usual rehabilitation

Locations

Country	Name	City	State
Belgium	UZGent	Gent
Belgium	UZLeuven Campus Pellenberg	Leuven
Netherlands	Zorggroep Adelante	Hoensbroek

Sponsors (7)

Lead Sponsor	Collaborator
Annemie Spooren	Adelante, Centre of Expertise in Rehabilitation and Audiology, Research Foundation Flanders, Universitaire Ziekenhuizen KU Leuven, University Hospital, Ghent, University of Aarhus, University of Sydney

Countries where clinical trial is conducted

Belgium,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	therapy difficulty	VAS	before session; after completion of session an average of 60 minutes
Other	session density	accelerometry	start intervention up to 10 weeks
Other	therapy perceived exertion	VAS	before session; after completion of session an average of 60 minutes
Primary	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
Primary	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	changes SICI	to evaluatie changes in Short interval intracortical inhibition	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
Secondary	changes SICF	short-interval intracortical facilitation	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
Secondary	changes in LICI	long-interval intracortical inhibition	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
Secondary	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
Secondary	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
Secondary	changes in behavioral measures: Upper extremity motor score	score on 50	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
Secondary	changes in Spinal Cord independence Measures	questionaire: self-care score	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
Secondary	changes in Van Lieshout Test	basis upper extremity skills	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
Secondary	changes in GRASSP	Grades redefined assessment of strength sensibility and Prehension	before intervention; at 10 weeks (after intervention) and at 6 months follow-up
Secondary	changes in hand held dynamometry	strength in hand	before intervention; at 10 weeks (after intervention) and at 6 months follow-up