Clinical trial NCT03443700: Randomized Controlled Trial on Robotic Exoskeleton in Spinal Cord Injury: Clinical Outcomes and Cortical Plasticity
Official title: Randomized Controlled Trial on Rehabilitation Training With a Robotic Anthropomorphic Exoskeleton in Patients With Motor Incomplete Spinal Cord Injury: Clinical Outcomes and Cortical Plasticity Indicators
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Spinal Cord Injuries
Keywords: SCI
gait
incomplete motor SCI
robotic gait training
locomotor training
walking training
rehabilitation
exoskeleton
EKSO
EKSO-GT
neuroplasticity
brain cortical plasticity
Lead sponsor: Azienda Usl di Bologna
Sponsor class: OTHER_GOV
Collaborators: name: IRCCS Institute of Neurological Sciences of Bologna (Italy)
name: Department of Biomedical and Neuromotor Sciences of the University of Bologna (Italy)
name: Montecatone Rehabilitation Institute S.p.A., Imola (Italy)
name: IRCCS Fondazione S. Lucia, Roma (Italy)
name: IRCCS Fondazione Ospedale S. Camillo, Venezia (Italy)
First posted: 2018-02-23
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: TREATMENT

Brief summary: The recent introduction of robotics for locomotor training in paraplegic patients, and in particular the use of anthropomorphic exoskeletons, has opened new frontiers in rehabilitation. Existing literature, though encouraging, is still scarce and studies demonstrating efficacy are highly heterogeneous and have a small sample size. Evidence is also needed about cortical plasticity after SCI, in conjunction with the use of innovative rehabilitation devices, through indicators like neurophysiological and neuroradiological markers, as the knowledge of such mechanisms is crucial to improve clinical outcomes. Cortical circuits controlling prosthetic devices are different from those controlling normal parts of the body and remodeling mechanisms following prosthetic use have been documented, but in conditions other than SCI.

The aims of this randomized controlled trial, with a 2-arm parallel-group design, are:

1. to evaluate and quantify the efficacy of locomotor rehabilitation with a robotic anthropomorphic exoskeleton (EKSO-GT) in terms of clinical and functional outcomes, and the persistence of such efficacy;
2. to investigate the presence and persistence of brain neuronal plasticity and cortical remodeling mechanisms underlying the robotic rehabilitation approach.

Fifty patients will be recruited and randomly assigned to 2 treatment arms. Both groups will follow a program of standard locomotor rehabilitation for 8 weeks. One group will also undergo an overground locomotor training with the EKSO-GT during the first 4 weeks.

Detailed description: The increasing incidence of incomplete Spinal Cord Injury (SCI) has raised new rehabilitation challenges. Recovery of walking is one of the top priorities in SCI persons and growing efforts have been pursued aimed at identifying effective alternative techniques for improving gait performance.

Standard rehabilitation approach has been so far the most widely used, but the recent introduction of anthropomorphic exoskeletons may open new frontiers in the field. Anthropomorphic exoskeletons have been developed to assist SCI patients with mobility, but there is also a certain optimism that they may have potentialities to improve walking patterns of incomplete SCI persons after a rehabilitation period with such devices is terminated. So far, however, while different systematic reviews and meta-analyses have reported on the safety of the training with such exoskeletons, there are no significant Fiftystudies on its efficacy. Along with this, central mechanisms underlying the anatomical and functional changes induced by these approaches have never been investigated in SCI.

This longitudinal randomized controlled trial, with a 2-arm parallel group design, aims at evaluating the efficacy of the training with an anthropomorphic, robotized exoskeleton (EKSO-GT, by Ekso Bionics), as "add-on" to the standard locomotor rehabilitation, in improving walking performance, when compared to the standard locomotor rehabilitation alone, in a population of patients with non-acute motor incomplete SCI. Along with this and other clinical outcomes, neurophysiological and structural markers of Central Nervous System (CNS) plasticity will be explored, aimed at capturing mechanisms underlying how anthropomorphic exoskeletons affect CNS plasticity.

Fifty patients will be recruited in 3 Italian rehabilitation hospitals setting and assigned to 2 groups, with an allocation ratio of 1:1, through a block randomization approach. One group will perform a 4-week standard locomotor training (sLT) alone, while the other will perform a 4-week period sLT plus a training with the EKSO-GT (sLT + EX-T). Afterwards, both groups will undergo a further 4-week sLT alone.

Patients will be evaluated at several time points (always when the exoskeleton is not worn): clinical outcomes will be assessed by means of clinical examinations, standardized tests and validated scales; neurophysiological modulations will be evaluated by means of paired Motor and Sensory Evoked Potentials and a study of Electroencephalographic (EEG) slow waves oscillations and signal coherence during sleep; anatomical and structural cortical modifications will be studied with brain functional Magnetic Resonance Imaging (fMRI).

It is expected that the overground locomotor training with a new-generation exoskeleton, as "add-on" to standard locomotor training, can further improve clinical outcomes (especially walking performance) in the studied population, and that such clinical improvements are underlined by mechanisms modulating synaptic plasticity occurring also at the CNS level.

Eligibility criteria: Inclusion Criteria:

* SCI due to traumatic or vascular etiology;
* Incomplete motor SCI (C or D in ASIA Impairment Scale);
* T1-L1 (included) neurological level;
* 1-5 years since injury;
* Functional gait ability (also with braces or orthoses);
* Sufficient Range of Motion (ROM) of lower limbs joints to achieve a reciprocal gait pattern and allow transition from sitting to vertical position;
* Stable clinical conditions;
* Minimum height of 157 cm;
* Maximum height of 188 cm;
* Maximum weight of 100 Kg;
* Maximum intertrochanteric distance of 46 cm;
* Cognitive integrity and full collaboration of the subject.
* Specific research informed consent signed.

Exclusion Criteria:

* Intensive walking rehabilitation training undergone in the last 3 months;
* Previous use of a robotic exoskeleton;
* Instability or major deformity of the spine;
* Lower limbs joints instability;
* Indication to spinal orthosis;
* Uncontrolled spasticity (score \> 3 of the Modified Ashworth Scale) in the majority of the muscle groups of the lower limbs;
* History of traumatic brain injury;
* Recent significant bone fractures, traumatic and/or pathological for the required training;
* Presence of neurogenic paraosteoarthropathies (POAN) at the onset or phlogistic phase;
* Discrepancy in femurs length (\> 1.3 cm) and legs length (\> 1.9 cm);
* Symptomatic orthostatic hypotension;
* Severe and recurrent uncontrolled autonomic dysreflexia;
* Cardiopulmonary comorbidities limiting physical effort;
* Skin lesions that can interfere with the study rehabilitation trainings;
* Documented psychiatric pathology;
* Contraindications to fMRI and polygraphic EEG execution;
* Contraindications to TMS;
* Ongoing pregnancy.

Primary outcomes:
measure: Change in walking performance
timeFrame: Baseline (initial visit post-randomization); week 4
Secondary outcomes:
measure: Change in walking performance
timeFrame: Baseline (initial visit post-randomization); week 8
measure: Change in walking endurance
timeFrame: Baseline (initial visit post-randomization); week 4; week 8
measure: Change in functional walking capacity
timeFrame: Baseline (initial visit post-randomization); week 4; week 8
measure: Change in spasticity
timeFrame: Baseline (initial visit post-randomization); week 4; week 8
measure: Change in pain
timeFrame: Baseline (initial visit post-randomization); every day, twice a day for the whole study period; overall appraisal at week 4 and week 8
measure: Change in mood state
timeFrame: Baseline (initial visit post-randomization); week 4; week 8
measure: Change in lower limbs muscle strength
timeFrame: Baseline (initial visit post-randomization); week 4; week 8
measure: Change in lower limbs muscle activation pattern
timeFrame: Baseline (initial visit post-randomization); week 4; week 8
measure: Change in entity of neuronal plasticity and cortical remodelling of motor cortical areas
timeFrame: Baseline (initial visit post-randomization); after the first locomotor training session; week 4; week 8
measure: Change in entity of neuronal plasticity and cortical remodelling of sensory cortical areas
timeFrame: Baseline (initial visit post-randomization); after the first locomotor training session; week 4; week 8
measure: Change in synaptic potentiation (neuroprosthetic learning)
timeFrame: Baseline (initial visit post-randomization); after the first locomotor training session; week 4
measure: Change in synaptic potentiation (neuroprosthetic learning)
timeFrame: Baseline (initial visit post-randomization); after the first locomotor training session; week 4
measure: Change in brain anatomy and cortical structure
timeFrame: Baseline (initial visit post-randomization); week 4; week 8
measure: Evaluation of patient's satisfaction for the training received
timeFrame: Week 4
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Azienda USL di Bologna, Istituto delle Scienze Neurologiche di Bologna (IRCCS ISNB)
state: BO
Study officials:
affiliation: IRCCS - ISNB
name: Elena Antelmi, MD
role: PRINCIPAL_INVESTIGATOR
References: