Cross Education for Upper Extremity Motor Function and Strength in Stroke

NCT ID: NCT06522191

Last Updated: 2025-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-29
• Study Completion Date: 2025-05-15

Brief Summary

Stroke is the leading cause of disability and mortality worldwide. The impact of stroke on the upper extremity functions is a common and important cause of long-term disability. Indeed, six months after the stroke, a considerable amount of patients are still unable to incorporate the affected upper limb into their daily activities. On the other hand, weaknesses are also observed in the "apparently normal" ipsilateral side of the lesion due to the presence of corticospinal fibers that do not cross to the contralateral side of the medulla.

This study aims to investigate the effects of cross-education (CE) using robotic rehabilitation on upper extremity motor function and strength in patients with stroke. Secondary objectives include assessing quality of life and activities of daily living.

Researchers will compare CE using robotic rehabilitation to the control group (CON) that received lower extremity-focused exercises to see if CE works to enhance rehabilitation outcomes.

Participants will receive 20 min, twice weekly CE (to the less affected upper limb) or CON before the RR intervention included in the PT intervention administered 5 days in a week for 5 weeks. They will be evaluated using the relevant outcomes at the beginning and the end of the study (5th week).

Detailed Description

After a stroke, upper extremity strength and skill deficits are predominant on the paretic side. In the chronic phase of stroke, patients with moderate to severe impairment also experience functional deficits on the less affected side, increasing dependence on this extremity during daily living activities. This situation highlights the necessity of incorporating the non-affected side into rehabilitation. Current rehabilitation approaches focus on intensive, highly repetitive, and task-oriented training. The aim within this framework is to induce neuroplasticity in the lesioned hemisphere to promote motor recovery. Techniques such as constraint-induced movement therapy are effective for inducing neuroplastic changes but are not suitable for all patient populations. Therefore, alternative treatment strategies are needed to induce neuroplastic changes in patients with greater upper extremity disability.

As stated above, promoting lesional hemispheric reorganization is crucial for recovery; however, the role of the contralesional motor cortex in recovery remains debated. Rehabilitation strategies must be tailored to the severity of motor impairment in patients. Cross-education (CE) emerges as a novel alternative rehabilitation strategy for individuals with moderate to severe motor impairment on the affected side. CE refers to the improvement in strength or skill in the contralateral limb through unilateral motor training. For stroke patients, this can be defined as gains in the paretic extremity through the training of the less affected side. Two main hypotheses underlie CE: the "cross-activation" and "bilateral access". The cross-activation model posits that unilateral activity stimulates both ipsilateral and contralateral cortical motor areas, whereas the bilateral access model suggests that training one side leads to adaptation in the untrained muscle on the opposite side via communication between motor areas in both hemispheres. Evidence indicates that in stroke patients, the corticospinal excitability of the affected hemisphere increases with CE-induced gains. functional magnetic resonance imaging (fMRI) studies in healthy individuals show that CE results in expanded activation areas in the contralateral sensorimotor cortex and the ipsilesional temporal lobe.

To date, studies on stroke involving CE have included strengthening exercises and task-oriented functional skill training, appearing effective in improving motor function and strength. Studies have shown that strength gains in stroke patients are greater compared to neurologically intact individuals. Robotic rehabilitation has proven effective in improving upper extremity motor functions and strength in stroke patients. However, no studies have investigated CE provided through unilateral robotic rehabilitation. This study aims to evaluate the effect of CE provided by an exoskeleton-type unilateral upper extremity robotic rehabilitation device on upper extremity motor function and strength.

Conditions

Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cross-Education (CE) Group

Participants in the CE group will receive repetitive task practice through a robotic rehabilitation (RR) device on the less-affected upper extremity for 20 minutes, twice a week, for 5 weeks, in addition to a physical therapy (PT) program provided 5 days a week. This CE training will be conducted prior to the RR sessions performed on the more affected UE within the PT intervention to facilitate cross-education and support motor priming. In this study, RR applications will utilize an intelligent feedback RR system.

Group Type: EXPERIMENTAL

Physiotherapy Training (PT)

Intervention Type: OTHER

Both groups received the same therapist-led standardized PT for 5 days a week including 2 days of RR plus 3 days of conventional rehabilitation (CR) for 5 weeks. RR training will be given 40 min per session using an intelligent feedback robotic system. The system allows patients to move a cursor to targets on a monitor using a unilateral exoskeleton robotic arm and handle, which supports shoulder, elbow, forearm, and optionally multi-joint movements. The system provides visual and auditory feedback, offering exergame training with 1Dimension (D), 2D, and 3D options adjustable to three levels (low to high). Exergames and their parameters will be customized based on each patient's capacity. The CR protocol consists of joint range-of-motion, correct movement, stretching and balance exercises, gait training (walking on level surfaces, stairs), strengthening of antagonist muscle pattern will be provided. Each CR session will last 45 min of active treatment.

Cross-Education Intervention

Intervention Type: DEVICE

Participants in the CE group will have the less affected upper extremity undergo game-based, unilateral, repetitive movement training using RR to enhance the effectiveness of the training to be provided to the affected side. Similar therapeutic games (exergames) planned for the more affected upper extremity will be selected through the unilateral exoskeleton RR device. As described in the PT section, upper extremity movements will be performed using the robotic arm and handle during the games. The difficulty level will be adjusted by the supervisor physiotherapist based on the grip threshold on the robotic handle, the game's difficulty level (low to high), workspace arrangement before each session, and suspension level according to the patient's needs. An approximately 20-minute program will be implemented, consisting of 8 games, each lasting about 2.5 minutes, tailored to the patient's capacity.

Control Group

Participants in the control group will be given lower extremity-focused exercises for 20 minutes, twice a week, for 5 weeks before the RR application included in the PT program, in order to eliminate the potential effect of the additional treatment provided in the study.

Group Type: SHAM_COMPARATOR

Physiotherapy Training (PT)

Intervention Type: OTHER

Both groups received the same therapist-led standardized PT for 5 days a week including 2 days of RR plus 3 days of conventional rehabilitation (CR) for 5 weeks. RR training will be given 40 min per session using an intelligent feedback robotic system. The system allows patients to move a cursor to targets on a monitor using a unilateral exoskeleton robotic arm and handle, which supports shoulder, elbow, forearm, and optionally multi-joint movements. The system provides visual and auditory feedback, offering exergame training with 1Dimension (D), 2D, and 3D options adjustable to three levels (low to high). Exergames and their parameters will be customized based on each patient's capacity. The CR protocol consists of joint range-of-motion, correct movement, stretching and balance exercises, gait training (walking on level surfaces, stairs), strengthening of antagonist muscle pattern will be provided. Each CR session will last 45 min of active treatment.

Control Intervention

Intervention Type: OTHER

The exercises to be administered in the control intervention will be selected based on the patient's level of impairment but will be planned without progression or intensity increase, and the involvement of the upper extremity will be kept to a minimum. The exercises will include lower limb joint range of motion exercises, weight bearing, weight shifting, and gait training.

Interventions

Physiotherapy Training (PT)

Both groups received the same therapist-led standardized PT for 5 days a week including 2 days of RR plus 3 days of conventional rehabilitation (CR) for 5 weeks. RR training will be given 40 min per session using an intelligent feedback robotic system. The system allows patients to move a cursor to targets on a monitor using a unilateral exoskeleton robotic arm and handle, which supports shoulder, elbow, forearm, and optionally multi-joint movements. The system provides visual and auditory feedback, offering exergame training with 1Dimension (D), 2D, and 3D options adjustable to three levels (low to high). Exergames and their parameters will be customized based on each patient's capacity. The CR protocol consists of joint range-of-motion, correct movement, stretching and balance exercises, gait training (walking on level surfaces, stairs), strengthening of antagonist muscle pattern will be provided. Each CR session will last 45 min of active treatment.

Intervention Type: OTHER

Cross-Education Intervention

Participants in the CE group will have the less affected upper extremity undergo game-based, unilateral, repetitive movement training using RR to enhance the effectiveness of the training to be provided to the affected side. Similar therapeutic games (exergames) planned for the more affected upper extremity will be selected through the unilateral exoskeleton RR device. As described in the PT section, upper extremity movements will be performed using the robotic arm and handle during the games. The difficulty level will be adjusted by the supervisor physiotherapist based on the grip threshold on the robotic handle, the game's difficulty level (low to high), workspace arrangement before each session, and suspension level according to the patient's needs. An approximately 20-minute program will be implemented, consisting of 8 games, each lasting about 2.5 minutes, tailored to the patient's capacity.

Intervention Type: DEVICE

Control Intervention

The exercises to be administered in the control intervention will be selected based on the patient's level of impairment but will be planned without progression or intensity increase, and the involvement of the upper extremity will be kept to a minimum. The exercises will include lower limb joint range of motion exercises, weight bearing, weight shifting, and gait training.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Chronic stroke more than 3 months of stroke onset
• History of first-ever unilateral ischemic or hemorrhagic stroke
• Upper extremity motor impairment; defined by an upper extremity score ≤42 on the Fugl Meyer upper extremity (FM-UE) assessment.
• No excessive spasticity in the affected arm (Modified Ashworth Scale ≤3)
• Having the ability to communicate and understand instructions (Mini-mental state examination ≥ 24)
• Being able to sit without needing any additional support and without leaning on a backrest

Exclusion Criteria

• Cardiovascular instability (severe, uncontrolled hypertension, coronary artery disease, etc.)
• Other neurological or musculoskeletal problems that can affect upper extremity functions
• Severe upper extremity pain defined as >7 on the Visual Analogue Scale
• Botox injections of the upper extremity within 3 months before enrollment

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istanbul University - Cerrahpasa

OTHER

Sponsor Role: lead

Responsible Party

Rüstem Mustafaoğlu

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fatih Aykut CAVDAR, BSc

Role: PRINCIPAL_INVESTIGATOR

Istanbul University-Cerrahpasa, Institute of Graduate Studies, Department of Physiotherapy and Rehabilitation

Rustem MUSTAFAOGLU, PhD

Role: STUDY_CHAIR

Istanbul University-Cerrahpasa, Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation

Belgin ERHAN, PhD

Role: STUDY_DIRECTOR

Physical Medicine and Rehabilitation Department, Faculty of Medicine, Istanbul Medeniyet University

Locations

Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi

Istanbul, Kadikoy, Turkey (Türkiye)

Countries

Turkey (Türkiye)

References

Stoykov ME, Corcos DM, Madhavan S. Movement-Based Priming: Clinical Applications and Neural Mechanisms. J Mot Behav. 2017 Jan-Feb;49(1):88-97. doi: 10.1080/00222895.2016.1250716. Epub 2017 Mar 1.

Reference Type: BACKGROUND

PMID: 28277966 (View on PubMed)

Lim H, Madhavan S. Effects of Cross-Education on Neural Adaptations Following Non-Paretic Limb Training in Stroke: A Scoping Review with Implications for Neurorehabilitation. J Mot Behav. 2023;55(1):111-124. doi: 10.1080/00222895.2022.2106935. Epub 2022 Aug 8.

Reference Type: BACKGROUND

PMID: 35940590 (View on PubMed)

Other Identifiers

2024/83

Identifier Type: -

Identifier Source: org_study_id