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

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ClinicalTrials.gov Identifier: NCT03443700
Recruitment Status : Not yet recruiting
First Posted : February 23, 2018
Last Update Posted : August 20, 2018
Sponsor:
Collaborators:
IRCCS Institute of Neurological Sciences of Bologna (Italy)
Department of Biomedical and Neuromotor Sciences of the University of Bologna (Italy)
Information provided by (Responsible Party):
Montecatone Rehabilitation Institute S.p.A.

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.

Forty 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.


Condition or disease Intervention/treatment Phase
Spinal Cord Injuries Device: EKSO-GT Procedure: Standard neurorehabilitation locomotor training Not Applicable

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 studies 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.

Forty patients will be recruited in a rehabilitation hospital 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 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized controlled trial
Masking: Single (Outcomes Assessor)
Masking Description: Because of the use of an evident Medical Device (exoskeleton), enrolled subjects cannot be blind about their assignment group, however objective and standardized clinical measure scales will be employed; moreover, assessments (also neurophysiological and neuroimaging ones) will be conducted by blind experts.
Primary Purpose: Treatment
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
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: sLT
Standard neurorehabilitation locomotor training during the whole study period (8 weeks).
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.

Experimental: sLT + EX-T
Standard neurorehabilitation locomotor training (sLT) during the whole study period (8 weeks), plus a training with a new-generation robotic anthropomorphic exoskeleton (EKSO-GT locomotor training) during the first 4 study weeks.
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.




Primary Outcome Measures :
  1. Change in walking performance [ Time Frame: Baseline (initial visit post-randomization); week 4 ]
    10-meter walk test


Secondary Outcome Measures :
  1. Change in walking performance [ Time Frame: Baseline (initial visit post-randomization); week 8 ]
    10-meter walk test

  2. Change in walking endurance [ Time Frame: Baseline (initial visit post-randomization); week 4; week 8 ]
    6-minute walk test

  3. Change in functional walking capacity [ Time Frame: Baseline (initial visit post-randomization); week 4; week 8 ]
    Walking Index for Spinal Cord Injury II (WISCI II)

  4. Change in spasticity [ Time Frame: Baseline (initial visit post-randomization); week 4; week 8 ]
    Modified Ashworth Scale

  5. Change in pain [ Time Frame: Baseline (initial visit post-randomization); every day, twice a day for the whole study period; overall appraisal at week 4 and week 8 ]
    Numeric Rating Scale (NRS)

  6. Change in mood state [ Time Frame: Baseline (initial visit post-randomization); week 4; week 8 ]
    Profile of Mood States questionnaire (POMS)

  7. Change in lower limbs muscle strength [ Time Frame: Baseline (initial visit post-randomization); week 4; week 8 ]
    Lower Extremity Motor Score (LEMS) of the American Spinal Injury Association (ASIA) Impairment Scale

  8. Change in lower limbs muscle activation pattern [ Time Frame: Baseline (initial visit post-randomization); week 4; week 8 ]
    Gait Dynamic Electromyography (DEMG)

  9. Change in entity of neuronal plasticity and cortical remodelling of motor cortical areas [ Time Frame: Baseline (initial visit post-randomization); after the first locomotor training session; week 4; week 8 ]
    Change in short-term intracortical inhibition through Motor Evoked Potentials (PEMs) elicited by Transcranial Magnetic Stimulation (TMS)

  10. Change in entity of neuronal plasticity and cortical remodelling of sensory cortical areas [ Time Frame: Baseline (initial visit post-randomization); after the first locomotor training session; week 4; week 8 ]
    Somatosensory Evoked Potentials (SSEs) at cortical level

  11. Change in synaptic potentiation (neuroprosthetic learning) [ Time Frame: Baseline (initial visit post-randomization); after the first locomotor training session; week 4 ]
    Analysis of slow-wave oscillations with Electroencephalographic (EEG) polysomnography (PSG)

  12. Change in brain anatomy and cortical structure [ Time Frame: Baseline (initial visit post-randomization); week 4; week 8 ]
    Functional Magnetic Resonance Imaging (fMRI)

  13. Evaluation of patient's satisfaction for the training received [ Time Frame: Week 4 ]
    Ad-hoc questionnaire



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03443700


Contacts
Contact: Ilaria Baroncini, MD +39 0542 632811 ilaria.baroncini@montecatone.com

Locations
Italy
Montecatone Rehabilitation Institute S.p.A.
Imola, BO, Italy, 40026
Sponsors and Collaborators
Montecatone Rehabilitation Institute S.p.A.
IRCCS Institute of Neurological Sciences of Bologna (Italy)
Department of Biomedical and Neuromotor Sciences of the University of Bologna (Italy)
Investigators
Principal Investigator: Jacopo Bonavita, MD Montecatone Rehabilitation Institute S.p.A.

Responsible Party: Montecatone Rehabilitation Institute S.p.A.
ClinicalTrials.gov Identifier: NCT03443700     History of Changes
Other Study ID Numbers: CE-17127
First Posted: February 23, 2018    Key Record Dates
Last Update Posted: August 20, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Montecatone Rehabilitation Institute S.p.A.:
SCI
gait
incomplete motor SCI
robotic gait training
locomotor training
walking training
rehabilitation
exoskeleton
EKSO
EKSO-GT
neuroplasticity
brain cortical plasticity

Additional relevant MeSH terms:
Wounds and Injuries
Spinal Cord Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System