Wearable Robotic System and Robotic Mirror Therapy in Spastic Hemiplegia Post Botulinum Toxin Injection

• ClinicalTrials.gov Identifier: NCT04826900
• Recruitment Status: Recruiting
• First Posted: April 1, 2021
• Last Update Posted: April 1, 2021
• Sponsor: Chang Gung Memorial Hospital
• Information provided by (Responsible Party): Chang Gung Memorial Hospital

Study Description

Brief Summary:

The purpose of this project is to examine and compare the immediate and long-term effects of combined Botulinum toxin type A(BoNT-A) injection with wearable robotic hand system (RT) and Robotic mirror therapy (RMT) in patients with spastic hemiplegic stroke.

Condition or disease	Intervention/treatment	Phase
Hemiplegia, Spastic; Spastic	Procedure: BoNT-A injections; Other: Robotic therapy (RT); Other: Robotic mirror therapy (RMT); Other: Functional task training	Not Applicable

Detailed Description:

Spasticity, a common impairment after stroke, has a profound impact on activity and participation for patients. BoNT-A injection combined with rehabilitation training is recommended to enhance functional recovery of patients with spastic hemiplegic stroke.

Patients with spasticity usually have lower motor function and worse sensory deficits than patients without spasticity. Designing the post BoNT-A injection rehabilitation program should consider the above issues. RT and MT are two interventions providing sensorimotor input for patient with low motor function. Combining both approaches (wearing robotic hand to do mirror therapy) might facilitate the sensorimotor cortex that controls movement and might augment somatosensory input and further treatment efficacy. It is unknown whether and how combining BoNT injection with bilateral RT vs with MT vs with RMT engenders differential effects on motor and related functional performance in patients with spastic hemiplegic stroke.

Forty-eight participants with chronic spastic hemiplegic stroke will be recruited and randomly assigned to one of 2 groups: RT, and RMT. All the post- injection interventions will be implemented 60 minutes/day, 3 days/week, for 8 weeks. At each training session all patients will receive 45-minute RT, or RMT, then 15-minute functional task training.

The outcome measures include 1) body function and structures: Fugl-Meyer Assessment, Modified Ashworth Scale, Medical Research Council scale, 2) activity and participation: Box and block test, Motor Activity Log, and Nottingham Extended Activities of Daily Living Scale, Action Research Arm Test. In addition, to directly reflect a patient's unique needs and goals, Goal Attainment Scaling will be assessed. Electroencephalography (EEG) and functional near infrared reflectance spectroscopy (NIRS) assessments will be done to assess the neurophysiologic effects of the 3 kinds of intervention. The outcome will be measured at pre-treatment,1-week after BoNT-A injection, post-treatment, and 3-month follow- up.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Masking Description: There will be a research code representing patients' identity, this code will not show patients' name, social security number, and home address. For the results of patients' visit and the diagnosis, the study moderator will maintain a confidential attitude and be careful to maintain patients' privacy.
• Primary Purpose: Treatment
• Official Title: A Randomized Control Trial to Compare the Effects Between Wearable Robotic System and Robotic Mirror Therapy in Patients With Spastic Hemiplegia Post Botulinum Toxin Injection: Neurophysiological and Behavior Outcomes
• Actual Study Start Date: August 1, 2019
• Estimated Primary Completion Date: January 23, 2022
• Estimated Study Completion Date: March 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Robotic Group; Training session included 45 minutes Robotic Therapy, followed by 15-minute functional training. The robotic group will receive 3 sessions per week, for 8 weeks.	Procedure: BoNT-A injections; Botox brand BoNT-A Purified Neurotoxin Complex, (Allergan Pharmaceuticals, Irvine, CA) will be prepared by diluting lyophilized toxin with 0.9% saline to a concentration of 33-100 U/ml. depending on the size of the target muscle. Location of the targeted muscle will be confirmed by using echo guide. The total dose range is 200 units to 500 units. The dose range of each target muscle is as below: 20 and 75 units for flexor carpi ulnaris and flexor carpi radials; 12.5-35 units per fascicle in the flexor digitorum sublimis and flexor digitorum profundus (maximum dose: 120 units for each of these muscles); 10-35 units in the flexor pollicis longus; 25-100 units in the brachioradial ; 50-200 units in the biceps brachii; and 25-75 units in the pronator teres; Other: Robotic therapy (RT); A wearable robotic hand system will be used in this study. The robotic hand system consisted with a wearable exoskeletal hand, sensor glove, and a control box. On the exoskeletal hand, there are five actuators on each of finger structure that can provide external power to bring individual finger moving. The sensor glove has five sensors that can detect the finger's posture during movement and then manipulates exoskeletal hand via the control box. The patient's unaffected hand wears the sensor glove, the affected hand wears the wearable exoskeleton hand, and the unaffected hand does the certain transitive and intransitive tasks as the mirror group, and then makes the affected hand do the same movements driven by the exoskeleton robotic hand.; Other: Functional task training; After either 45 minutes of RT or RMT, all participants receive 15 minutes of training in functional tasks. The functional tasks included taking up and holding bowl or using eating utensils , bringing a cup for drinking, drying sucks by clips, open ing or closing door , turning on or off the light, cleaning the table or window and so on . The functional tasks training will be bases on the needs and ability of patients.
Experimental: Robotic Mirror Group; Training session included 45 minutes Robotic Mirror Therapy, followed by 15-minute functional training. The robotic group will receive 3 sessions per week, for 8 weeks.	Procedure: BoNT-A injections; Botox brand BoNT-A Purified Neurotoxin Complex, (Allergan Pharmaceuticals, Irvine, CA) will be prepared by diluting lyophilized toxin with 0.9% saline to a concentration of 33-100 U/ml. depending on the size of the target muscle. Location of the targeted muscle will be confirmed by using echo guide. The total dose range is 200 units to 500 units. The dose range of each target muscle is as below: 20 and 75 units for flexor carpi ulnaris and flexor carpi radials; 12.5-35 units per fascicle in the flexor digitorum sublimis and flexor digitorum profundus (maximum dose: 120 units for each of these muscles); 10-35 units in the flexor pollicis longus; 25-100 units in the brachioradial ; 50-200 units in the biceps brachii; and 25-75 units in the pronator teres; Other: Robotic mirror therapy (RMT); Wearable robotic hand system and mirror system will be used in this group.. The patients in the group will wear the robotic hand to do the mirror therapy. The patient's unaffected hand wears the sensor glove, the affected hand wears the wearable exoskeletal hand, a mirror box with a mirror will be placed in the patient 's midsagittal plane beside the unaffected hand to block his or her view of the affected hand. The patient's unaffected hand does the certain transitive and intransitive tasks and the patient will be instructed to look at the reflection of the unaffected hand in the mirror as if it is the affected hand (the visual input). At the same time the affected hand will be passively moved by the exoskeleton robotic hand which is under the .control of the unaffected hand.; Other: Functional task training; After either 45 minutes of RT or RMT, all participants receive 15 minutes of training in functional tasks. The functional tasks included taking up and holding bowl or using eating utensils , bringing a cup for drinking, drying sucks by clips, open ing or closing door , turning on or off the light, cleaning the table or window and so on . The functional tasks training will be bases on the needs and ability of patients.

Outcome Measures

Primary Outcome Measures :

1. Fugl-Meyer Assessment (FMA) [ Time Frame: Change from baseline at 5 months ]
   The upper extremity (UE) subscale of the FMA will be used to assess neuromusculoskeletal and movement related functions. It consi sts of 33 upper extremity items for the reflexes and movement of shoulder, elbow, forearm, wrist, hand, and coordination/speed. They are scored on a 3 point ordinal scale (0 cannot perform, 1 performs partially, 2 performs fully). Higher score indicates better motor function of UE, and the maximum score is 66. Satisfactory psychometric properties of the FMA have been demonstrated.
2. Medical Research Council scale (MRC) [ Time Frame: Change from baseline at 5 months ]
   The MRC scale will be used to examine the muscle strength of the affected arm (Medical Research Council, 1976). The MRC scale is a reliable measurement which ranges from 0 (no contraction) to 5 (normal power). The muscle strength will be measured at the elbow flexors/extensors, wrist flexors/extensors, and finger extensors by using the MRC in this project.
3. Modified Ashworth Scale (MAS) [ Time Frame: Change from baseline at 5 months ]
   Spasticity of skeletal muscle in upper extremity will be evaluated by using the MAS scale .It uses a 6-point scale to score the average resistance to passive movement for each join with higher score indicating higher spasticity. The MAS has showngood reliability and validity.
4. Box and Block test (BBT) [ Time Frame: Change from baseline at 5 months ]
   The BBT, which evaluates manual dexterity of the paretic UE, uses a wooden box that has two equally sized compartments. Cubes were placed in one compartment, and the participants were instructed to move the cubes to the other compartment one by one and as quickly as possible within 60 secs. The score was determined by calculating the number of cubes carried across the partition. The BBT has high test-retest reliability in participants with stroke.
5. Motor Activity Log (MAL) [ Time Frame: Change from baseline at 5 months ]
   The MAL is a semi-structured interview to rate how well [quality of movement scale (QOM)] and how much [amount of use scale (AOU)] they use their affected upper extremity in 30 daily activities using a 6-point scale. Higher scores represent better performance. The MAL has established reliability, validity, and responsiveness in patients with stroke. The MAL will be used to measure daily use of the affected upper limb in daily life in this project.
6. Nottingham Extended Activities of Daily Living Scale (NEADL) [ Time Frame: Change from baseline at 5 months ]
   The NEADL is a measure of the requirement for help in performing instrumental activities of daily living (IADL) for patients with stroke. The NEADL has 22 items divided into 4 areas of daily life: mobility, kitchen, domestic, and leisure activities. Higher scores indicate greater independence. The reliability, validity, and responsiveness of the NEADL have well-established in patients with stroke.

Secondary Outcome Measures :

1. Near Infrared Reflectance Spectroscopy (NIRS) [ Time Frame: 1.5 hours ]
   We will use subjective report and near-infrared spectroscopy (NIRS) to assess the attention level during the 3 interventions. NIRS can measure the changes in oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR) concentration in the microvasculature of the brain during time-sequential, real-time monitoring. The relative concentration changes of HbO2 and HbR can be calculated by detecting the relative optical transparency variation of red and near-infrared light penetrating through the brain tissue. A wireless multi-blood flow parameter monitoring system will be used to monitor the change in HbO2, HbR , total-hemoglobin (HbT) concentrations, and the tissue oxygen saturation in frontal area simultaneously. We will apply the modified Beer-Lambert law and spatially resolved spectroscopy methods to measure the concentration of HbO2 (μM ∙ min-1) and HHb (μM ∙ min-1) in the region of interest. In this study, we inferred mental concentration on the basis of changes in oxygenation.
2. Electroencephalography assessment [ Time Frame: 1.5 hours ]
   The EEG technique, has considerable advantages to detect how rehabilitation can change brain systems. The high temporal resolution of EEG allows monitoring brain activity during movement execution

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Clinical and imagine diagnosis of a first or recurrent unilateral stroke ≥ 3 months
• Finger flexor muscles spasticity (modified Ashworth scale of ≥ 1+)
• Initial motor part of UE of FMA score ranging from 10 to 56 indicating moderate to severe movement impairment
• No serious cognitive impairment (i.e., Mini Mental State Exam score > 20)
• Age ≥ 20 years

Exclusion Criteria:

• Pregnant
• With bilateral hemispheric or cerebellar lesions
• Sever aphasia
• Significant visual field deficits or hemineglect
• Contraindication for BoNT-A injection
• Treatment with BoNT-A within 6 months before recruitment
• Any fixed joint contracture of the affected upper limb
• A history of orthopedic or other neurological diseases and/or medical conditions that would prevent adherence to the rehabilitation protocol

Contacts and Locations

Contacts

Contact: Hung Jen-Wen; +886975056689; hung0702@cgmh.org.tw

Locations

Taiwan

Department of Rehabilitation, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan; Recruiting

Kaohsiung, Taiwan, 833

Contact: Jen-Wen Hung, MD +886975056689

Sponsors and Collaborators

Chang Gung Memorial Hospital

Investigators

• Principal Investigator: Hung Jen-Wen; Chang Gung Memorial Hospital-Kaohsiung Medical Center

More Information

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• Responsible Party: Chang Gung Memorial Hospital
• ClinicalTrials.gov Identifier: NCT04826900
• Other Study ID Numbers: NRMPG8J0211
• First Posted: April 1, 2021
• Last Update Posted: April 1, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Chang Gung Memorial Hospital:

Stroke rehabilitation; Spasticity; Botulinum toxin type A injection; Mirror therapy; Robot

Additional relevant MeSH terms:

Muscle Spasticity; Hemiplegia; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Paralysis; incobotulinumtoxinA; Neuromuscular Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents