Clinical trial NCT06065384: Neural Plasticity and Motor Recovery After Early and Intensive Upper Extremity Motor Training in People with C-SCI
Official title: Neural Plasticity and Motor Recovery After Early and Intensive Upper Extremity Motor Training in People with Cervical Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Spinal Cord Injuries
Keywords: spinal cord rehabilitation
therapy dose
neural plasticity
motor recovery
upper limb training
Lead sponsor: Hasselt University
Sponsor class: OTHER
Collaborators: name: Research Foundation Flanders
name: University of Aarhus
name: University of Sydney
name: University Hospital, Ghent
name: Universitaire Ziekenhuizen KU Leuven
name: Adelante, Centre of Expertise in Rehabilitation and Audiology
name: Rehabilitation Hospital RevArte
First posted: 2023-10-03
Enrollment: 44
Sex: ALL
Minimum age (years): 16
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 (\<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 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.

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); SICF (short interval intracortical inhibition); Peripheral plasticity: NET (Nerve excitability testing) en MScanFit MUNE.

Eligibility criteria: 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. 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+) and will be excluded in the presence of contraindications for TMS application such as epilepsy, metal implants in the brain, defibrillator, pacemaker,r and pregnancy

Primary outcomes:
measure: changes in single pulse TMS: resting motor threshold
timeFrame: - before intervention; at 4 weeks (inbetween measure), at 8 weeks (after intervention) and at 6 months follow-up
measure: changes in GRASSP
timeFrame: - before intervention; at 8 weeks (after intervention) and at 6 months follow-up
measure: Changes in Compound Muscle Action Potential (CMAP)
timeFrame: - before intervention; at 4 weeks (inbetween measure), at 8 weeks (after intervention) and at 6 months follow-up
Secondary outcomes:
measure: changes SICI
timeFrame: - before intervention; at 8 weeks (after intervention) and at 6 months follow-up
measure: changes SICF
timeFrame: - before intervention; at 8 weeks (after intervention) and at 6 months follow-up
measure: Single-pulse TMS: Stimulus Response Curve
timeFrame: - before intervention; at 4 weeks (inbetween measure), at 8 weeks (after intervention) and at 6 months follow-up
measure: changes in LICI
timeFrame: - before intervention; at 8 weeks (after intervention) and at 6 months follow-up
measure: changes in MscanFit MUNE
timeFrame: - before intervention; at 4 weeks (inbetween measure), at 8 weeks (after intervention) and at 6 months follow-up
measure: changes in single pulse TMS: mapping
timeFrame: - before intervention; at 8 weeks (after intervention) and at 6 months follow-up
measure: changes in NET (Nerve excitability testing)
timeFrame: - before intervention; at 4 weeks (inbetween measure), at 8 weeks (after intervention) and at 6 months follow-up
measure: changes in behavioral measures: Upper extremity motor score
timeFrame: - before intervention; at 8 weeks (after intervention) and at 6 months follow-up
measure: changes in Spinal Cord independence Measures
timeFrame: - before intervention; at 8 weeks (after intervention) and at 6 months follow-up
measure: changes in Van Lieshout Test
timeFrame: - before intervention; at 8 weeks (after intervention) and at 6 months follow-up
measure: changes in hand held dynamometry
timeFrame: - before intervention; at 8 weeks (after intervention) and at 6 months follow-up
Other outcomes:
measure: therapy difficulty
timeFrame: before session; after completion of session an average of 60 minutes
measure: session density
timeFrame: - measurement of one week during the 2., 5. and 8. week of intervention duration
measure: therapy perceived exertion
timeFrame: before session; after completion of session an average of 60 minutes
Locations:
city: Antwerp
country: Belgium
facility: Revalidatieziekenhuis RevArte
city: Gent
country: Belgium
facility: UZGent
city: Leuven
country: Belgium
facility: UZLeuven Campus Pellenberg
city: Hoensbroek
country: Netherlands
facility: Zorggroep Adelante
Study officials:
affiliation: Hasselt University
name: Annemie Spooren, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: