Randomized Controlled Trial on Robotic Exoskeleton in Spinal Cord Injury: Clinical Outcomes and Cortical Plasticity

Spinal Cord Injuries Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03443700
• Other study ID #: CE-19072
• Secondary ID: 347-2019-DISP-AU
• Status: Recruiting
• Phase: N/A
• Start date: December 10, 2020
• Est. completion date: November 2022

Study information

• Verified date: December 2021
• Source: Azienda Usl di Bologna
• Contact: Elena Antelmi, MD
• Phone: +39-3293526335
• Email: elenaantelmi[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: November 2022
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Wounds and Injuries

Intervention

Device:
• EKSO-GT
Each rehabilitation session with EKSO-GT will last (operating time) 30-40 minutes. Such training will be carried out for 3 sessions per week, during the first 4 consecutive weeks of the study period (i.e. 12 total sessions per patient).

Procedure:
• Standard neurorehabilitation locomotor training
Neurorehabilitation locomotor training will be performed according to standardized protocols shared within the scientific community, during the whole 8-week study period, 5 times per week, twice a day, for a total of about 2,5 hours per day.

Locations

Country	Name	City	State
Italy	Azienda USL di Bologna, Istituto delle Scienze Neurologiche di Bologna (IRCCS ISNB)	Bologna	BO

Sponsors (6)

Lead Sponsor	Collaborator
Azienda Usl di Bologna	Department of Biomedical and Neuromotor Sciences of the University of Bologna (Italy), IRCCS Fondazione Ospedale S. Camillo, Venezia (Italy), IRCCS Fondazione S. Lucia, Roma (Italy), IRCCS Institute of Neurological Sciences of Bologna (Italy), Montecatone Rehabilitation Institute S.p.A., Imola (Italy)

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in walking performance	10-meter walk test	Baseline (initial visit post-randomization); week 4
Secondary	Change in walking performance	10-meter walk test	Baseline (initial visit post-randomization); week 8
Secondary	Change in walking endurance	6-minute walk test	Baseline (initial visit post-randomization); week 4; week 8
Secondary	Change in functional walking capacity	Walking Index for Spinal Cord Injury II (WISCI II)	Baseline (initial visit post-randomization); week 4; week 8
Secondary	Change in spasticity	Modified Ashworth Scale	Baseline (initial visit post-randomization); week 4; week 8
Secondary	Change in pain	Numeric Rating Scale (NRS)	Baseline (initial visit post-randomization); every day, twice a day for the whole study period; overall appraisal at week 4 and week 8
Secondary	Change in mood state	Profile of Mood States questionnaire (POMS)	Baseline (initial visit post-randomization); week 4; week 8
Secondary	Change in lower limbs muscle strength	Lower Extremity Motor Score (LEMS) of the American Spinal Injury Association (ASIA) Impairment Scale	Baseline (initial visit post-randomization); week 4; week 8
Secondary	Change in lower limbs muscle activation pattern	Gait Dynamic Electromyography (DEMG)	Baseline (initial visit post-randomization); week 4; week 8
Secondary	Change in entity of neuronal plasticity and cortical remodelling of motor cortical areas	Change in short-term intracortical inhibition through Motor Evoked Potentials (PEMs) elicited by Transcranial Magnetic Stimulation (TMS)	Baseline (initial visit post-randomization); after the first locomotor training session; week 4; week 8
Secondary	Change in entity of neuronal plasticity and cortical remodelling of sensory cortical areas	Somatosensory Evoked Potentials (SSEs) at cortical level	Baseline (initial visit post-randomization); after the first locomotor training session; week 4; week 8
Secondary	Change in synaptic potentiation (neuroprosthetic learning)	Analysis of slow-wave oscillations with Electroencephalographic (EEG) polysomnography (PSG)	Baseline (initial visit post-randomization); after the first locomotor training session; week 4
Secondary	Change in synaptic potentiation (neuroprosthetic learning)	Analysis of EEG coherence signal	Baseline (initial visit post-randomization); after the first locomotor training session; week 4
Secondary	Change in brain anatomy and cortical structure	Functional Magnetic Resonance Imaging (fMRI)	Baseline (initial visit post-randomization); week 4; week 8
Secondary	Evaluation of patient's satisfaction for the training received	Ad-hoc questionnaire	Week 4