Safety and Efficacy Evaluation of the Robotic Enhanced Error Training of Upper Limb Function in Post-stroke and Post TBI Participants

A Prospective, Randomized, Open-label, Two-arms, Multi Center Feasibility Study to Evaluate the Safety and Efficacy of the PlaXtreme Device for Rehabilitation of the Hand in Post-stroke and Post TBI Participants

Background: Cerebrovascular accident [CVA or commonly known as stroke] and traumatic brain injury (TBI) are common causes of morbidity, and motor impairments. Many stroke and TBI patients encounter severe functional impairments of their arm and/or hand. Recent studies have indicated that robotic training can improve upper limb function by enabling repetitive, adaptive, and intensive training.

One type of robotic training is error enhancement during three-dimensional movements. The goal of this approach is to elicit better accuracy, stability, fluidity and range of motion during reaching.

Previous research indicated the potential of robotic training with error enhancement as a viable clinical intervention for individuals facing motor deficits.

Objectives: To evaluate the safety and efficacy of a new robotic system based on error enhancement and intended for rehabilitation of motor hand functions of post-stroke and TBI patients.

Methods: A randomized, multi-center study with an open-label design. The study sample will consist of 96 participants who will be randomized into 2 separate groups. The intervention group consisting of 48 patients will receive training with the new robotic system, while the control group consisting of additional 48 patients will receive only standard practice treatments (with no exposure to the new robotic system). The outcomes of safety (adverse events and treatment tolerability), and efficacy (motor function, speed, tone, and spasticity) will be assessed and compared between the two groups. The assessment of the outcomes will be conducted at four different time points: (1) prior to the initiation of the four-week intervention, (2) after 2 weeks of intervention, (3) at the conclusion of the intervention, and (4) at a three-month follow-up session.

Background: Stroke and traumatic brain injury (TBI) are leading causes for morbidity, hospitalization, and extended injury of motor system as well as movement learning. It has been proven that roughly 85% of stroke survivors suffer from weakness in their upper limbs, and around 40% of stroke survivors will suffer from severe handicap in their paretic arm, negatively affecting their independence and quality of life. Statically, about 50% - 70% of survivors will recover enough to enable daily use of their arm. These numbers indicate that although rehabilitation for stroke patients is evident, there remains a need for more effective methods.

Traditional rehabilitative methods are often time-consuming and labor-intensive. Only a few of these methods induce slightly improved arm function, and a full recovery is often not achieved. Recently, studies have indicated that robotic training has promise for improving functional abilities among stroke survivors by enabling repetitive, adaptive, intensive, and accurate control of task complexity during the rehabilitation period. One type of robotic training that is particularly promising is error enhancement; this utilizes the adaptive capabilities of the nervous system to improve fine motor function of the arm.

Study Objectives: To evaluate the change in the upper limb function amongst post-stroke and post-TBI patients undergoing error enhancement treatment compared to a control group in the following domains:

1. Motor Function (Fugl-Meyer Assessment, Action Research Arm Test (ARAT), pinch and grip tests)
2. Speed (Box and Blocks Assessment)
3. Tone and Spasticity (Modified Ashworth Scale)

In addition, this study will examine the safety and patient tolerability of the device.

Methods Population: A total of 96 participants will be recruited within 3 medical centers participating in the study. The recruitment will take place between 14 days and up to 18 months after the onset of the stroke or brain injury.

Recruitment: Electronic medical records of newly hospitalized patients will be screened to identify potential study participants. All eligible patients will be offered to participate. After obtaining informed consent, an intake session will take place for screening and evaluation purposes, conducted by a qualified occupational therapist. Patients successfully passing the screening session will undergo randomization to one of the two study arms with 1:1 ratio in each of the medical centers conducting the study.

All the treatments will be conducted a separate occupational therapist who will be blinded to the patient allocation group. Patients in the intervention arm will undergo training sessions with the robotic device, 3 times a week for a period up to 4 weeks, while the patients in the control arm will receive standard rehabilitative care.

Patients in both groups will undergo additional evaluation sessions at the following time points: after 2 weeks of intervention, at the conclusion of the intervention (4 weeks), and at a three-month follow-up session.

Inclusion Criteria:

• Hemiparesis due to first stroke (ischemic or hemorrhagic) or TBI;
• At least 14 days after the stroke or brain injury onset;
• No more than 18 months after stroke or brain injury onset;
• At least 4 weeks of remaining hospitalization in inpatient or outpatient rehabilitation ward;
• Voluntary provided informed consent obtained prior to any screening procedures;
• Cognitive status: Montreal Cognitive Assessment (MoCA test) score ≥ 22 or Mini Mental State Examination (MMSE) score > 24;
• Upper extremity function: Score between 35 and 52 points out of 66 on the Fugl- Meyer (FG) test with sub scores of 21-32/36 for the upper arm and 14-20/24 for the wrist and hand.

Exclusion Criteria:

• Complete paralysis of the affected side;
• Uncontrolled epilepsy;
• Upper-limb pain > 6 on 10-point Visual Analogue Scale (VAS);
• Concomitant or past medical conditions that might interfere with the study (i.e. hemi spatial neglect, orthopedic problems, etc.);
• Current participation in other interventional clinical study;
• Fingers spasticity score on the affected hand > 3 on Modified Ashworth Scale (MAS);
• Pregnant or nursing women.