Multi-segmental Robotic and Technological Upper Limb Rehabilitation in Stroke
Condition: Stroke
MeSH terms: Stroke
Study type: Interventional

Summary: 
      Stroke is frequently associated with significant disability and impaired quality of life.
      Persistent motor impairment is common with often incomplete recovery of motor function in
      response to rehabilitation, mainly in the upper limbs. Robot-mediated therapy has been
      proposed as a viable approach for the rehabilitation of the upper limb, but as the evidence
      quality is low, more rigorous studies are needed. Previous studies have focused on the
      effects of devices acting on a limited number of joints, often limiting the workspace on a
      plane. This study aims to evaluate the efficacy of a multi-set of robotic and technological
      devices for the rehabilitation of the upper limb in sub-acute stroke patients.
    

Detailed description: 
      Stroke is the first cause of disability in the world, with a very high social impact.
      Recovery is partial in 85% of stroke survivors, 35% of whom have a persisting serious
      disability. The increase in lifespan is leading to a rise in the incidence of stroke, and
      therefore to a rise in the number of people requiring a rehabilitation program.
      Rehabilitation programs are mainly focused on walking recovery, with insufficient attention
      being paid to upper limb recovery. Thirty to 60% of patients treated with conventional
      therapy present functional deficits of the paretic arm, resulting in an impairment of
      activities of daily living.

      Robot-mediated therapy (RT) has been proposed in the literature as a viable approach for the
      rehabilitation of the upper limb. A first meta-analysis of 262 subjects showed that when the
      duration/intensity of conventional therapy (CT) is matched with that of the robot-assisted
      therapy, no difference exists between the two groups in terms of motor recovery, activities
      of daily living, strength or motor control; instead, when the RT is added to CT, a greater
      effectiveness can be observed, when compared with regular CT alone (5). A subsequent
      meta-analysis by Mehrholz et al., including 19 trials (involving 666 subjects), showed that
      RT was more effective than other interventions in improving patients' activities of daily
      living (SMD 0.43, 95% confidence interval (CI) 0.11 to 0.75, P = 0.009, I2 = 67%). In the
      same sample, stratified by time since disease onset, the analysis confirmed that RT was more
      effective in improving the activities of daily living in the 224 acute and sub-acute patients
      (within 3 months of stroke onset) (SMD 0.64, 95% CI 0.14 to 1.15, P=0.01, I2 =69%). The same
      findings were not confirmed in 334 chronic patients (more than 3 months after stroke) (SMD
      0.85, 95% CI -0.27 to 1.97, P=0.14, I2 =94%). As for the other outcomes, robotic therapy was
      more effective in improving upper extremity function (SMD 0.45, 95% CI 0.20 to 0.69, P =
      0.0004, I2 = 45%), but not muscular strength (SMD 0.48, 95% CI -0.06 to 1.03, P = 0.08, I2 =
      79%). Finally, RT was well accepted by patients, there was no marked increase in the number
      of drop-outs, and serious adverse events were rare and unrelated to the robotic treatment
      (6).

      In an update of their meta-analysis, published in 2015, the same research team confirmed that
      RT was more effective than other therapies in improving activities of daily living (SMD 0.37,
      95% confidence interval (CI) 0.11 to 0.64, P = 0.005, I² = 62%), motor function (SMD 0.35,
      95% CI 0.18 to 0.51, P < 0.0001, I² = 36%) and strength (SMD 0.36, 95% CI 0.01 to 0.70, P =
      0.04, I² = 72%) of the upper limb. RT was well accepted by patients, there was no marked
      increase in the number of drop-outs (RD 0.00, 95% CI -0.02 to 0.03, P = 0.84, I² = 0%), and
      serious adverse events were rare and unrelated to the robotic treatment. However, the authors
      concluded that the evidence quality was low, highlighting the need for more rigorous studies.

      It should be noted that the authors of the review highlighted the fact that the studies
      reviewed were heterogeneous in terms of study design (two arms, four arms, parallel groups or
      cross-over, duration of follow-up and selection criteria), of the devices used for the
      therapeutic treatment, of the patients' characteristics (time since disease onset), of the
      methodological protocols (methods of randomization, of the blindness of the outcome assessors
      to group allocation, and of the presence or absence of an intention to treat analysis).

      However, the authors emphasized that limitations such as the inability to blind the therapist
      and participants, i.e. the so-called contamination (provision of the intervention to the
      control group), and co-intervention (when the same therapist unintentionally provides
      additional care to either treatment or comparison group) has often been present in
      rehabilitation studies. Moreover, they pointed out that sometimes the sample is selected
      according to comorbidities, age, spasticity or pain; instead, in clinical practice patients
      are often older, and the prevalence of comorbidity, pain, spasticity and/or limitations of
      articular function is higher than that reported in the studies analyzed. Therefore, inclusion
      criteria that allow the effects of a robotic treatment to be evaluated on a larger sample of
      patients with stroke, with clinical characteristics as close as possible to the real-world
      clinical setting, are desirable.

      Many authors have highlighted the impact on costs and the greater sustainability of the RT
      when compared with the CT. The latter requires a ratio of one therapist to one patient, while
      RT, after adequate training of the therapist, allows a ratio of one therapist to every three
      or four patients, depending on the technology used.

      RT allows patients' improvements to be assessed even after a single treatment session, to
      constantly monitor the rehabilitation program and therefore to better define the best
      rehabilitation strategies. In fact, thanks to the possibility the systems available, it is
      possible to customize the treatment based on the patients' clinical characteristics. Last but
      not least, robotic devices involve and motivate patients, providing them with visual and
      auditory feedback through virtual reality programs in the form of games. Training progresses
      through increasingly difficult stages that can be linked by patients to their own progress.
      This becomes an important stimulus to increase the active participation of patients in the
      rehabilitation program.

      Almost all scientific papers in the literature have focused on the effects of the use of one
      or, at most, two robotic devices, compared with a conventional approach.

      However, even though the anatomy and the motor function of the upper limbs, especially the
      hand, is extremely complex, all but a very few commercial devices act on a limited number of
      joints and limit the workspace on a plane. By contrast, during conventional therapy the whole
      upper limb is routinely treated and the three-dimensional space, in which the upper limb is
      normally required to move to accomplish daily activities, is normally explored. In the light
      of the above, it is very difficult to compare the effects of robotic and traditional
      approaches.

      This results in the need for a multi-set of robots and electromechanical systems, each of
      which acts on a different joint and/or on a different plane, in upper limb rehabilitation in
      stroke patients. To the best of our knowledge, the effects of a similar approach, i.e. the
      use of a multi-set of robotic devices to restore motor function in patients with stroke, have
      never been compared with those of a conventional approach. Moreover, the effects should
      ideally be explored on a large sample of subjects that are representative of clinical
      practice.

      Hypothesis. The rationale behind the study is that a multi-set of robotic devices used to
      treat the whole upper limb may be more effective than conventional treatments in improving
      upper limb motor performance, since they raise the degree of motivation and participation
      among patients, and provide a more intensive, standardized and individualized treatment.

      Therefore, the investigators wish to verify this hypothesis on a large sample of subjects,
      within a multicenter study using the same multi-set of robotic devices and the same outcome
      measures, to obtain better-quality scientific evidence than that currently available in the
      literature.

      Aim: to assess, using evidence-based criteria (RCT), the effectiveness of a rehabilitation
      program targeting all the upper limb joints in stroke patients, using a multi-set of robotic
      and technological systems, by comparing it with that of a conventional approach.
    

Intervention name(s): Amadeo, Pablo, Diego and Motore.; Conventional rehabilitation
Intervention type(s): Device; Other
Intervention description(s): In the robotic rehabilitation group, patients will be treated with the following systems: Amadeo, Pablo and Diego (Tyromotion GmbH, Austria), and Motore (Humanware, Italy). A ratio of one therapist to every 3 or 4 patients will be used, depending on the patient's severity. The rehabilitation treatment will be performed daily for 45 minutes, for 5 days per week, for 6 weeks. A total of 30 sessions will be performed.; In the conventional rehabilitation group, patients will undergo a conventional treatment with a ratio of one therapist to one patient. The rehabilitation treatment will be performed daily for 45 minutes, for 5 days per week, for 6 weeks. A total of 30 sessions will be performed.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Stroke; Upper limb; Robotic rehabilitation