Clinical trial NCT06890481: Robotic rEhabilitation sCenario fOr patieNts With NeglECT
Official title: Collaborative Development of a Virtual Reality Scenario, Integrated Into a Robotic Upper Limb Rehabilitation Device, for the Treatment of Unilateral Spatial Negligence (NSU) Through Mutisensory Stimulation: Feasibility and Usability Pilot Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Stroke
Ischemic Stroke
Haemorrhagic Stroke
Neglect, Hemispatial
Keywords: stroke
robotics
end-effector
upper-limbs
rehabilitation
neglect
usability
Lead sponsor: Fondazione Don Carlo Gnocchi Onlus
Sponsor class: OTHER
Collaborators: name: Humanware S.r.l.
First posted: 2025-03-24
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The goal of this pilot clinical trial is to develop an integrated motor and cognitive rehabilitation program and evaluate the usability and acceptability of a new virtual reality scenario designed for the MOTORE device. This study will focus on the rehabilitation of the upper limbs in post-stroke patients with plegia and left-sided hemi-inattention. The main questions it aims to answer are:

* The evaluation of the usability and acceptability of the newly developed scenario
* The evaluation of the effects of the new scenario on patients' hemi-inattention
* The evaluation of changes in upper limb functional parameters

Participants will undergo a total of 13 rehabilitation sessions, each lasting 45 minutes, using the new scenario, including an initial and final assessment.

Detailed description: Stroke in the right hemisphere can provoke both motor and cognitive symptoms. Hemi-inattention is a cognitive deficit typical of right hemispheric damage, with an incidence ranging from 12% to 95%. This deficit can manifest as difficulty in detecting and responding to stimuli from the left side of space, without any motor or sensory impairments that could justify the deficit. Hemi-inattention is usually associated with lesions in the inferior and superior parietal areas and, sometimes, in parts of the frontal area and the white matter connecting the parietal to the prefrontal areas. Hemi-inattention significantly compromises patients' quality of life and can negatively impact both motor and cognitive rehabilitation outcomes.

According to the theory of premotor spatial attention, brain attention and motor circuits are closely connected. Thus, it is possible to hypothesize that somatosensory activation in the contralesional space could stimulate the neural networks responsible for spatial representation and the conscious perception of stimuli. Some studies have attempted to verify this hypothesis by developing ad-hoc rehabilitation programs based on these theoretical principles. These studies can be divided into:

Studies investigating upper limb active mobilization, which require the activation of residual motor capabilities Studies investigating upper limb passive mobilization. It is widely accepted that hemi-inattention is a multisensory deficit, i.e., involving several sensory channels, and that a rehabilitation program based on joint stimulation of different channels can be effective.

Robot-assisted rehabilitation for the upper limbs, especially in hemiparetic patients, has gained growing interest in recent years, given the possibility of intensive treatment while still ensuring patient safety \[8-9\]. However, few studies have focused on the use of robotic devices, whose training modality often involves serious games, on cognitive aspects, particularly on hemi-inattention.

Even though preliminary and based on small sample sizes, these studies suggest a potential advantage of integrated cognitive and motor intervention for the rehabilitation of the upper limb and hemi-inattention. Indeed, the use of serious games and virtual reality scenarios can promote a synergistic effect of motor and cognitive stimulation. Furthermore, robotic rehabilitation can offer additional advantages, such as the "game effect," the ability to adapt the exercise difficulty level to the patient's performance, and the possibility of providing real-time feedback to the patient.

MOTORE is a planar end-effector robot for upper limb rehabilitation. In the literature, studies on the efficacy of this device in improving speed, strength, and spasticity of the upper limbs are available. However, no evidence is available regarding its use in treating hemi-inattention in post-stroke patients.

For this reason, this study aims to extend the use of the MOTORE device to the cognitive domain by creating a new virtual reality scenario for the robot. The scenario will consist of a sequential visual stimuli exercise with intra-session adaptive difficulty, designed to guide the patient's attention toward the neglected side of space through the combined use of visual and auditory stimuli and motor requests. The new scenario will be evaluated for usability with plegic post-stroke patients suffering from left hemi-inattention.

The novelty of the current study lies in the application of a multisensory approach, using auditory and visual stimuli, along with movement supported by the robot, to direct the patient's attention to the stimulus placed on the side of space affected by hemi-inattention.

Eligibility criteria: Inclusion Criteria:

* Presence of a diagnosis of right hemispheric stroke
* Presence of a diagnosis of hemi-inattention (Apple test)
* Presence of left hemiplegia (Fugl-Meyer Assessment Upper Limb ≤58)
* Adjusted Montreal Cognitive Assessment \<20
* Written informed consent

Exclusion Criteria:

* Presence of cognitive decline prior to the event
* Presence of previous stroke events
* Presence of osteoarticular rigidity (e.g., ankylosis, functional limitations with traumatic or degenerative origin) or spasticity in the affected upper limb (Modified Ashworth Scale ≥3 on shoulder, elbow, or wrist)
* Inability to maintain a sitting position
* Presence of severe visual disabilities
* Recent injection of botulinum toxin in the upper limb or planned injection of botulinum toxin during the study period
* Orthopaedic, neurological, or psychiatric disorders that could interfere with the study procedures and motor or cognitive assessments
* Unstable fractures of the upper limb
* Severe osteoporosis
* Skin lesions on the upper limb

Primary outcomes:
measure: Usability of the device
timeFrame: Evaluated at session 12 (after the treatment) at an average of 2 weeks
measure: Acceptability of the device for the operator
timeFrame: Evaluated at session 12 (after the treatment) at an average of 2 weeks
Secondary outcomes:
measure: Variation of symptoms connected to hemi-inattention
timeFrame: Evaluated at session 2 (before the beginning of treatment) and at session 12 (after treatment)
measure: Functional direct effect of the device
timeFrame: Evaluated at session 2 (before the beginning of treatment) and at session 12 (after treatment)
Other outcomes:
Locations:
city: Firenze
country: Italy
facility: IRCCS Fondazione Don Carlo Gnocchi onlus
Study officials:
References:
citation: Robertson, I. H., & Hawkins, K. (1999). Limb activation and unilateral neglect. Neurocase, 5(2), 153-160
citation: Heilman, K. M., Watson, R. T., & Valenstein, E. (1993). Neglect and related disorders. In K. M. Heilman & E. Valenstein (Eds.), Clinical neuropsychology (pp. 279-336). Oxford University Press.
citation: Rizzolatti G, Berti A. Neglect as a neural representation deficit. Rev Neurol (Paris). 1990;146(10):626-34.
citation: Robertson, I. H., Hogg, K., & McMillan, T. M. (1998). Rehabilitation of unilateral neglect: improving function by contralesional limb activation. Neuropsychological rehabilitation, 8(1), 19-29
citation: Gainotti G, Perri R, Cappa A. Left hand movements and right hemisphere activation in unilateral spatial neglect: a test of the interhemispheric imbalance hypothesis. Neuropsychologia. 2002;40(8):1350-5. doi: 10.1016/s0028-3932(01)00211-1.
citation: Frassinetti F, Rossi M, Ladavas E. Passive limb movements improve visual neglect. Neuropsychologia. 2001;39(7):725-33. doi: 10.1016/s0028-3932(00)00156-1.
citation: Jacobs S, Brozzoli C, Farne A. Neglect: a multisensory deficit? Neuropsychologia. 2012 May;50(6):1029-44. doi: 10.1016/j.neuropsychologia.2012.03.018. Epub 2012 Mar 28.
citation: Mehrholz J, Pollock A, Pohl M, Kugler J, Elsner B. Systematic review with network meta-analysis of randomized controlled trials of robotic-assisted arm training for improving activities of daily living and upper limb function after stroke. J Neuroeng Rehabil. 2020 Jun 30;17(1):83. doi: 10.1186/s12984-020-00715-0.
citation: Bertani R, Melegari C, De Cola MC, Bramanti A, Bramanti P, Calabro RS. Effects of robot-assisted upper limb rehabilitation in stroke patients: a systematic review with meta-analysis. Neurol Sci. 2017 Sep;38(9):1561-1569. doi: 10.1007/s10072-017-2995-5. Epub 2017 May 24.
citation: Varalta V, Picelli A, Fonte C, Montemezzi G, La Marchina E, Smania N. Effects of contralesional robot-assisted hand training in patients with unilateral spatial neglect following stroke: a case series study. J Neuroeng Rehabil. 2014 Dec 5;11:160. doi: 10.1186/1743-0003-11-160.
citation: Choi YS, Lee KW, Lee JH, Kim SB, Park GT, Lee SJ. The Effect of an Upper Limb Rehabilitation Robot on Hemispatial Neglect in Stroke Patients. Ann Rehabil Med. 2016 Aug;40(4):611-9. doi: 10.5535/arm.2016.40.4.611. Epub 2016 Aug 24.
citation: Heins, S., Dehem, S., Montedoro, V., Dehez, B., Edwards, M., Stoquart, G., ... & Lejeune, T. (2017, April). Robotic-assisted serious game for motor and cognitive post-stroke rehabilitation. In 2017 IEEE 5th International Conference on Serious Games and Applications for Health (SeGAH) (pp. 1-8). IEEE.
citation: Mazzoleni S, Battini E, Crecchi R, Dario P, Posteraro F. Upper limb robot-assisted therapy in subacute and chronic stroke patients using an innovative end-effector haptic device: A pilot study. NeuroRehabilitation. 2018;42(1):43-52. doi: 10.3233/NRE-172166.