Clinical trial NCT04077073: Effects of Device-assisted Practice of ADL on Arm/Hand Recovery in Individuals With Moderate to Severe Stroke
Official title: Effects of Device-assisted Practice of Activities of Daily Living in a Close-to-normal Pattern on Upper Extremity Motor Recovery in Individuals With Moderate to Severe Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke
Keywords: stroke rehabilitation
hand opening
flexion synergy
robot assisted treatment
functional electrical stimulation
motor recovery
brain plasticity
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2019-09-04
Enrollment: 54
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A large number of post-stroke survivors cannot functionally use their paretic upper extremity (UE). This study therefore investigates effects of device-assisted practice of activities of daily living (ADL) in a close-to-normal pattern on UE motor recovery in individuals with moderate to severe stroke by measuring intervention-induced changes in clinical outcomes, UE kinematics, and functional and morphologic neuroplasticity. Positive findings may impact current clinical practice by pushing towards implementing device-assisted practice of ADLs and have the potential to benefit a large population.

Detailed description: Thirty subjects for each group will be recruited. A REDCap database for this study will be setup to manage every step involved in the protocol. All the potential subjects will go through standardized steps:

1. Experienced research team members will conduct pre-screening of subjects from the Clinical Neuroscience Research Registry, which is maintained by the Physical Therapy and Human Movement Sciences (PTHMS) department at Northwestern University. Recruitment will also be conducted via flyers in various rehabilitation centers in the Chicagoland. The investigators will start the recruitment by an 'initial phone contact' to introduce the study and confirm the interests for participation. Once confirmed, a standardized 'phone screening' will be followed to partially go through the questions related to eligibility. Once passed all the questions over phone, a lab-based eligibility test will be scheduled at the department of PTHMS. During the first visit, the investigators will explain the study and answer all the related questions from potential participants. The paper consent form will be signed and dated by the individual once he/she agrees to participate, and a copy of the signed consent form will be given to the participant. Following consent, the blinded assessor will determine the eligibility using the inclusion and exclusion criteria.
2. The treating therapist will determine the settings of reliable and intuitive control of the paretic hand (ReIn-Hand) device. A 3D scan will be made to enable the produce of subject-specific ReIn-Hand device.
3. Qualified participants will undergo 2 baseline clinical assessments within 2 weeks.
4. All the enrolled participants will be randomly assigned to the either experimental or control group with the balance in Upper Extremity Fugl-Meyer Assessment (FMA) scores of the 2 groups. Randomization results will be concealed to the assessor all the time and will be only assessable to treating therapists and biostatisticians on the day for the first session of the assigned intervention.
5. The investigators will collect individual's magnetic resonance imaging (MRI) data and electroencephalogram (EEG) data within two weeks prior to the intervention. MRI scans will be performed at Northwestern University's Center for Translation Imaging. For EEG data collection, the investigators will first measure a subject's maximal voluntary torque (MVT) in the direction of shoulder abduction (SABD), maximum finger grasping forces of the paretic upper extremity (UE), maximum hand pentagon area, defined as the area formed by the tips of thumb and fingers, of the non-paretic hand when the hand is maximally stretched on a tabletop, and subject's upper- and forearm lengths for normalization purposes. For the hand opening task, participants' arm will be rested on the virtual table at the home position. Participants will relax in the home position for 5-7s and then to self-initiate maximal hand opening for 2s, without blinking or eye moving. For the hand opening with SABD loading, participants will perform the maximal hand opening while lifting the arm above table against 50% of his/her SABD MVT after 5-7s resting on the home position. A set of 60-70 trials will be collected for each condition, in a block randomized way (20-30 trials per block). Rest periods of \~15 s between trials and \~10 min between blocks will be included to avoid fatigue.
6. Intervention All participants will participate in a 24-session intervention, \~2 hours per session, 3 sessions per week, for 8 weeks in total. Research participants, training PTs, and clinical evaluators will be blind to group assignment.

   For all intervention, research participants will be seated with straps across the chest and waist to prevent unwanted trunk movement. The training technicians will stretch the paretic UE for up to 15 minutes. The ReIn-Hand device will be attached to the paretic UE and then positioned at a home position in 75° SABD, 30° shoulder flexion, and 60° elbow flexion.

   The first session will be a 'parameter adjusting session', during which the training PT will determine training parameters, including: 1) SABD load, 2) target(jar) distance, 3) jar width, 4) jar weight, 5) jar height, and 6) jar orientation. These training parameters will be established both on the table condition and using a robot. The robot modulates the supporting force in Z-direction applied to the arm while participants are required to lift the arm, thus changing the SABD load. The SABD load will be set as the maximum load that allows the participant to actively reach the target distance and achieve a ReIn-Hand mediated hand opening no less than 4 cm between the tips of the thumb and index fingers. After establishing SABD load, all the additional parameters (2-6) will be set, first with the established SABD load as following: Target distance is 70% of the distance of the max reach of the paretic UE when fully supported on a frictionless table created by the robot; Jar width will be increased in 0.5 cm increments, by adding padding around the jar, to the max width the participant can achieve with the ReIn-Hand; Jar height (i.e., distance from the lowest part of the jar to the surface of the table) will be set as 2 cm increments to the max height the participant can successfully (and painlessly) reach the jar; Jar orientation (i.e., the relation of the long axis of the jar to the table surface) will be set as 2° increments to the maximum amount that allows the participant to successfully grasp the jar; and Jar weight will be increased in 100 g increments, stopping if the participant experiences pain or cannot lift the jar. The Training PT will then repeat the steps 2-6 to determine these parameters (2-6); however, this time without robot support and thus using a height-adjustable table.

   Once the intervention parameters are set, the training technician will guide the participant to perform 'reaching-grasping-retrieving-and- releasing' (GR3) activities using these parameters. Participants in the experimental group will be trained using the robot. Their forearm of a participant will be attached to an orthosis, which will be firmly attached to the robot. Participants in the experimental group will be trained on a regular table. All training sessions will consist of 40 trials (about 1 hour) of GR3 activities, which include: 1) Reaching towards a plastic jar (diameter=3cm, weight=30g when empty); 2) Activating finger/wrist extensor muscles to trigger the ReIn-Hand device, which in turn assists the opening of the paretic hand while reaching; 3) Grasping the jar; 4) Retrieving the jar to the home position and placing it on the table; and 5) Releasing the jar. To avoid fatigue, a resting time of 20-30 seconds will be provided between trials. Participants in the control group will be encouraged to perform GR3 activities with the arm above the table.

   A successful trial requires the completion of all five tasks required during one trial: Reaching towards a plastic jar, triggering the ReIn-Hand device, grasping the jar, retrieving the jar to the home position, and placing it on the table, and releasing the jar. An unsuccessful trial is defined as the failure to complete one of the five tasks during one trial. The result of each of the 40 trials will be recorded by the training technician.

   The Training PT will review the training performance after each session to determine if adjustment of parameters is necessary for the next session. If a participant successfully completes 30/40 trials in 2 successive sessions, the training PT will re-adjust all the parameters at the following session to progressively challenge the participant. New parameters then will be implemented by the training technician during the following session.
7. Weekly outcome measures. The blinded clinical assessor will measure the following outcomes weekly: Box and Blocks Test, Quantitative Measure of Hand Opening and Closing, and Cutaneous Sensory Touch Threshold.
8. The blinded clinical assessor will check participant's sensory and motor function using the same clinical assessments as that used for baseline within 1 week after the intervention.
9. Within one week after the end of intervention, the investigators will repeat the neural imaging and biomechanical data collection, using the same protocols as stated before.
10. Three-month follow-up. Three months after the intervention, the blinded clinical assessor will check participant's sensory and motor function using the same clinical assessments as stated before. To maximize the retention, the investigators will have a clear and standardized communication of our expectations of the participant over the course of the study. For each participant, the project coordinator will generate a personal timetable with scheduling of experiments. Flexibility of appointments will be included. Finally, the project coordinator will call the participants about at 7 days and then 1 day before the scheduled 3-month follow up to remind the last assessment.

AE and SAE reporting Adverse event (AE) report form has been implemented in the RedCap database, which can be used at any time. The investigators will report all AEs to the Northwestern Institutional Review Board (IRB) per established policies and requirements. The investigators will create AE reports every six months to review for trends and troubleshoot any issues that arise and require study protocol revision. If any AEs are reported that require follow-up medical care, the investigators will immediately refer the participant back to his/her physician team.

Serious adverse events (SAEs) that are unanticipated, serious, and possibility related to the study intervention will be reported to the Independent Monitor(s), IRB, and National Institute of Child Health and Human Development (NICHD) in accordance with requirements. Unexpected fatal or life-threatening AEs related to the intervention will be reported to the Northwestern IRB in accordance with IRB requirements within 24 hours, and to the NICHD program Officer with 7 days. Other serious and unexpected AEs related to the intervention will also be reported to the Northwestern IRB in accordance with IRB requirements within 24 hours, and to the NICHD program Official within 15 days. Anticipated or unrelated SAEs will be handled in a less urgent manner but will be reported to the Independent Monitor(s), IRB, NICHD, and other oversight organizations in accordance with their requirements. In the annual AE summary, the Independent Monitor(s) Report will state that they have reviewed all AE reports.

Eligibility criteria: Inclusion Criteria:

1. Age between 21-80
2. Paresis confined to one side, with substantial motor impairment of the upper limb and some residual voluntary movement (UE FMA in the range of 10-40/66, CMSA_H stage of the hand section \<=4)
3. Capacity to provide informed consent
4. Ability to elevate their limb against gravity up to at least 75 degrees of shoulder flexion and to generate some active elbow extension
5. Ability to open hand with a thumb-to-index finger distance ≥4 cm, with the assistance of the ReIn-Hand device with the help of a physical therapist
6. MRI compatible
7. Discharged from all forms of physical rehabilitation
8. Intact skin on the hemiparetic arm
9. Be tolerate sitting for no less than 1 hour
10. Montreal Cognitive Assessment (MoCA) score \>=23

Exclusion Criteria:

1. Motor or sensory impairment in the non-affected limb
2. Any brainstem and/or cerebellar lesion
3. Severe concurrent medical problems (e.g. cardiorespiratory impairment, uncontrolled hypertension, inflammatory joint disease)
4. History of neurologic disorder other than stroke (Parkinson's Disease, Acute Lateral Sclerosis, Multiple Sclerosis, Traumatic Brain Injury, peripheral neuropathy, Amyotrophic lateral sclerosis, spinal cord injury, Dementia)
5. Any acute or chronic painful condition in the upper extremities or spine, indicated by a score ≥5 on a 10-point visual analog scale
6. Using cardiac pacemaker, implanted cardioverter defibrillator, neurostimulation system inside the brain or spinal cord, bone growth box fusion stimulation
7. Seizure in the last 6 months
8. Severe upper extremity sensory impairment indicated by absent sensation on the tactile sensation subscale (light touch and pressure items) of the Revised Nottingham Assessment of Somato-Sensations (score\<4)
9. Chemo denervation: botulinum toxin, dysport, or Myobloc or phenol block injection to any portion of the paretic UE within the last 6 months, or phenol/alcohol injections \<12 months before participation
10. Unable to passively attain 90 degrees of shoulder flexion and abduction, measured using a goniometer based on adapted methods
11. Flexion contractures larger than 45 degrees in the elbow, wrist, metacarpophalangeal joints (MCP) and interphalangeal joints (IP) of thumb and index finger
12. Pregnant or planning to become pregnant
13. Participating in any experimental rehabilitation or drug studies
14. Inability to attend intervention sessions 3 times a week during 8 weeks, as well as to assessments/evaluations and follow up
15. Upper extremity musculoskeletal impairment limiting function prior to stroke
16. Currently using oxygen
17. Upper limb amputation

Primary outcomes:
measure: Change in Box and Blocks Test (BBT) from baseline to 1 week post-intervention
timeFrame: This will be measured twice pre-intervention (within 1 week prior to intervention), 1 time per week during intervention, 1 time immediately after conclusion of intervention (within 1 week), and 1 time at the 3 month follow up
Secondary outcomes:
measure: Change in Quantitative measure of hand opening area and closing force
timeFrame: This will be measured twice pre-intervention (within 1 week prior to intervention), 1 time per week during intervention, 1 time immediately after conclusion of intervention (within 1 week), and 1 time at the 3 month follow up
measure: Change in Cutaneous Sensory Touch Threshold using Semmes-Weinstein Monofilaments
timeFrame: This will be measured twice pre-intervention (within 1 week prior to intervention), 1 time per week during intervention, 1 time immediately after conclusion of intervention (within 1 week), and 1 time at the 3 month follow up
measure: Change in Upper extremity Fugl-Meyer Assessment Score
timeFrame: This will be measured twice pre-intervention (within 1 week prior to intervention), 1 time immediately after conclusion of intervention (within 1 week), and 1 time at the 3 month follow up.
measure: Change in Sensory Assessment (Stereognosis)
timeFrame: This will be measured twice pre-intervention (within 1 week prior to intervention), 1 time immediately after conclusion of intervention (within 1 week), and 1 time at the 3 month follow up
measure: Change in Stroke Impact Scale (SIS)
timeFrame: This will be measured twice pre-intervention (within 1 week prior to intervention), 1 time immediately after conclusion of intervention (within 1 week), and 1 time at the 3 month follow up.
measure: Change in Motor Activity Log (MAL)
timeFrame: This will be measured twice pre-intervention (within 1 week prior to intervention), 1 time immediately after conclusion of intervention (within 1 week), and 1 time at the 3 month follow up.
measure: Change in Action Research Arm Test (ARAT)
timeFrame: This will be measured twice pre-intervention (within 1 week prior to intervention), 1 time immediately after conclusion of intervention (within 1 week), and 1 time at the 3 month follow up.
measure: Change in Chedoke McMaster Stroke Assessment (CMSA) Hand Subscale
timeFrame: This will be measured twice pre-intervention (within 1 week prior to intervention), 1 time immediately after conclusion of intervention (within 1 week), and 1 time at the 3 month follow up.
measure: Change in Revised Nottingham Sensory Assessment: Kinaesthesia Subscale
timeFrame: This will be measured twice pre-intervention (within 1 week prior to intervention), 1 time immediately after conclusion of intervention (within 1 week), and 1 time at the 3 month follow up.
measure: Change in Coupling forces generated by shoulder and elbow while opening hand with or without lifting
timeFrame: This will be measured 1 time pre-intervention (within 1 week prior to intervention), and 1 time immediately after conclusion of intervention (within 1 week).
measure: Change in Hand pentagon area (HPA) while opening with or without lifting
timeFrame: This will be measured 1 time pre-intervention (within 1 week prior to intervention), and 1 time immediately after conclusion of intervention (within 1 week).
measure: Change in Laterality Index for the cortical activity related to hand opening
timeFrame: This will be measured 1 time pre-intervention (within 1 week prior to intervention), and 1 time immediately after conclusion of intervention (within 1 week).
measure: Change in Cortical activity ratio (CAR)
timeFrame: This will be measured 1 time pre-intervention (within 1 week prior to intervention), and 1 time immediately after conclusion of intervention (within 1 week).
measure: Change in Gray matter (GM) density
timeFrame: This will be measured 1 time pre-intervention (within 1 week prior to intervention), and 1 time immediately after conclusion of intervention (within 1 week).
measure: Change in Fractional anisotropy (FA) of bilateral cortico-fugal tracks
timeFrame: This will be measured 1 time pre-intervention (within 1 week prior to intervention), and 1 time immediately after conclusion of intervention (within 1 week).
Other outcomes:
Locations:
city: Chicago
country: United States
facility: 645 N Michigan Ave, Suite 1100
state: Illinois
city: Chicago
country: United States
facility: Northwestern University, Dept. of PTHMS
state: Illinois
Study officials:
affiliation: Northwestern University
name: Jun Yao, PhD
role: PRINCIPAL_INVESTIGATOR
References: