An Early Phase 1 interventional study of Neuromuscular coordination enhancement (NICE) intervention and EMG Amplitude Biofeedback Exercise in Chronic Stroke-related Upper-extremity Motor Impairment and Motor Module-guided Rehabilitation Targeting Impaired Intermuscular Coordination and Motor Recovery, sponsored by University of Houston. Not yet recruiting at 1 site in United States. Open to participants aged 21 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-18.
Sponsored by University of Houston · Early Phase 1, Interventional, and Treatment
The objective of this study is to develop Neuro-Intermuscular Coordination Enhancement (NICE) rehabilitation, a novel neuromuscular control signal-guided strategy that visually guides stroke patients to individually activate motor modules through human-machine interaction. Ultimately, the development will lead to better clinical motor recovery, better quality of life, and lowered healthcare costs associated with the impairment.
Stroke is the leading cause of severe long-term disability, affecting 9.4 million Americans. Each year around 800,000 people suffer a stroke even in the USA. Chronic upper extremity motor impairment is a major contributing factor to disability; functional use of the affected UE in daily life is a key factor for increased independence, return to work, and overall quality of life. Thus, effective and innovative treatment to address long-term disability is both a major public health need and an economic necessity.
This study is an early-stage, randomized controlled rehabilitation trial designed to evaluate the clinical effects, feasibility, transfer of therapeutic gains, and exploratory neurophysiological correlates of Neuro-Intermuscular Coordination Enhancement (NICE) in individuals with chronic stroke and upper-extremity hemiparesis.
Forty-eight participants will be enrolled to obtain a target analyzable sample of 40 participants. Eligible participants will be randomized to either: (1) NICE, a motor module-guided rehabilitation intervention using isometric human-machine interaction and real-time EMG-based visual feedback to retrain impaired intermuscular coordination patterns; or (2) an active comparator consisting of dose-matched EMG amplitude biofeedback exercise. Both interventions will be delivered three times per week for six weeks (18 total sessions). Participants will complete assessments at baseline, immediately post-intervention, and at 10- and 18-week follow-up time points.
Outcomes will include standardized clinical measures of upper-extremity motor impairment and function, measures of intermuscular coordination derived from surface electromyography, kinematic measures obtained during untrained dynamic motor tasks, and EEG-based measures of brain activity and connectivity.
The primary objective is to determine whether NICE improves upper-extremity motor impairment relative to the active comparator. Secondary objectives are to evaluate intervention-related changes in intermuscular coordination and transfer of therapeutic gains to untrained motor behaviors. Exploratory objectives are to characterize rehabilitation-associated neurophysiological changes and examine relationships among EEG-derived biomarkers, intermuscular coordination, and clinical recovery outcomes.
Inclusion criteria for individuals after stroke are:
Exclusion criteria for individuals after stroke are:
Inclusion criteria for healthy individuals are:
Exclusion criteria for healthy individuals are:
Post-stroke participants will perform a center-out task by activating individual motor modules (generating coordinated isometric contractions of muscles) to move the cursor on a screen while electromyographic (EMG) signals are recorded. Activation of each muscle (or muscle group) will be mapped to 1 of 4 directions within the multi-dimensional cursor space. We will derive the cursor position in real time using Motor module activation magnitudes recorded from arm muscles.
Other: Neuromuscular coordination enhancement (NICE) intervention
Participants will perform a center-out target matching tasks where individual muscle EMGs are used to move a cursor on the visual feedback display to match one of 4 different targets presented to them. Here, just the EMG amplitude, and not the coordination is focused on.
Other: EMG Amplitude Biofeedback Exercise
Neuro-Intermuscular Coordination Enhancement (NICE) is a motor module-guided rehabilitation intervention designed to improve upper-extremity motor recovery after stroke by retraining impaired intermuscular coordination patterns. Participants perform isometric upper-extremity force-generation tasks using a human-machine interface while receiving real-time visual feedback derived from motor module recruitment signals calculated from surface electromyography (EMG). Individualized motor module targets are derived from the participant's less-affected upper extremity and used to guide selective recruitment of impaired coordination patterns in the more-affected upper extremity. Participants will complete 18 one-hour training sessions over six weeks (3 sessions/week). During training, participants perform repetitive target-matching tasks that require preferential recruitment of specific motor modules while minimizing unintended activation of non-target modules.
EMG Amplitude Biofeedback Exercise is an active comparator rehabilitation intervention designed to improve upper-extremity motor function after stroke through targeted muscle activation training. Participants perform isometric upper-extremity exercises using a human-machine interface with real-time EMG amplitude-based visual feedback. Individualized muscle activation targets derived from the less-affected upper extremity guide training of the more-affected upper extremity. Participants will complete 18 one-hour sessions over 6 weeks (3 sessions/week).
Fugl-Meyer Assessment (FMA) score
Motor impairment after stroke will be measured by upper extremity FMA (UE-FMA). The maximum UE-FMA motor score is 66 (i.e., 0: complete motor impairment; 66: normal motor performance). Each item is scored on a 3-point scale (0 = cannot perform, 1 = performs partially, 2 = performs fully). The FMA score reflects the level of upper extremity motor impairment.
Time frame: Baseline, six- week, 10-week, and 18-week follow-ups.
Similarity Score of Intermuscular Coordination Patterns (or Motor Modules)
Surface EMGs will be recorded from 8 key arm muscles during a 54-target isometric force generation task. A dimensionality reduction method (non-negative matrix factorization (NNMF)) will be applied to identify intermuscular coordination patterns - operational definition of motor modules in the field of motor neuroscience. They are mathematically 8-dimensional unit vectors. Similarity score is the scalar product (or dot product) between a pair of intermuscular coordination patterns in comparison (i.e., motor modules). We compute the similarity score between the less-affected and the more-affected arms. Also, surface EMGs will be recorded from 8 key arm muscles during 3D dynamic reaching tasks. NNMF will be applied to EMGs to identify and compare intermuscular coordination patterns. Similarity score is the scalar product between motor modules (i.e., intermuscular coordination patters) of the more-affected arm in stroke group and dominant arm in healthy group.
Time frame: Baseline, six- week, 10-week, and 18-week follow-ups.
Kinematic Synergy Similarity Score
Kinematic synergies are a representation of multi-joint coordination. It will be identified using NNMF algorithm applied to the joint kinematic data obtained from 3D dynamic point-to-point reaching tasks. Kinematic synergy similarity between stroke and healthy will be calculated using their scalar product.
Time frame: Baseline, six-week, 10-week, and 18-week follow-ups.
Pairwise joint angle-to-angle correlation value
Pairwise joint angle-to-angle correlation is a way to see the joint coupling using kinematic data. It will be calculated using Pearson's correlation coefficient between joint angles during the point-to-point reaching task.
Time frame: Baseline, six- week, 10-week, and 18-week follow-ups.
Active range of motion
The active range of motion will be calculated from full active range tasks for shoulder flexion/extension, internal/external rotation, abduction/adduction, elbow flexion/extension, and wrist pronation/supination. Kinematic joint positions and angles will be used to calculate the same.
Time frame: Baseline, six-week, 10-week, and 18-week follow-ups.
EEG Spectral power ratios
EEG-derived spectral power ratios will be calculated, in resting and task conditions, across different frequency bands (delta, theta, alpha, beta, gamma) and different events (onset, successful match, etc.) across four different directions of target match.
Time frame: Baseline and six-week follow-up.
EEG-derived Brain Symmetry Index
The revised brain symmetry index with EEG signals will be computed in the resting state during eyes open and closed conditions.
Time frame: Baseline and six-week follow-up.
Cortico-muscular connectivity
Functional connectivity using a directed transfer function will be computed to identify the information flow and coherence among EEG and EMG signals in the desired brain region and muscle activation associated with directional 4-target isometric force generation.
Time frame: Baseline and six-week follow-up.
Cortico-cortical connectivity
Functional connectivity using a directed transfer function will be computed to identify the information flow and coherence among EEG signals from different regions of interest (sources, e.g., ipsi and contralesional fronto-parietal regions, primary motor cortex and somatosensory cortices).
Time frame: Baseline and six-week follow-up.
Participant recruitment rate
Recruitment rate will be calculated as the number of participants enrolled per month during the recruitment period. This is a feasibility outcome.
Time frame: From participant recruitment beginning to enrollment completion
Participant intervention adherence
Intervention adherence will be calculated as the percentage of scheduled intervention sessions completed by each participant. This is a feasibility outcome.
Time frame: Throughout the 6-week intervention period.
Participant Tolerance of the Intervention
Participant tolerance will be measured as the number and percentage of participants who complete intervention sessions without stopping due to discomfort, fatigue, pain, or other intolerance-related reasons. This is a feasibility outcome.
Time frame: Throughout the 6-week intervention period.
Intervention fidelity
Intervention fidelity will be calculated as the percentage of intervention sessions delivered according to the study protocol. This is a feasibility outcome.
Time frame: Throughout the 6-week intervention period.
Dose equivalence between the intervention groups
Dose equivalence will be assessed by comparing total intervention dose between groups, measured as total minutes of training and/or number of completed sessions per participant. This is a feasibility outcome.
Time frame: Throughout the 6-week intervention period.
NICE-specific training feasibility
NICE-specific feasibility will be assessed as the percentage of NICE intervention sessions in which the NICE training system/protocol is successfully implemented as intended. This is a feasibility outcome.
Time frame: Throughout the 6-week intervention period.
Participant retention rate
Retention rate will be calculated as the percentage of enrolled participants who complete each scheduled follow-up assessment. This is a feasibility outcome.
Time frame: Baseline, six-week, 10-week, and 18- week follow-ups and throughout the 6-week intervention period.
Successful acquisition of study data
Successful data acquisition will be calculated as the percentage of expected EMG, EEG, kinematic, and clinical outcome datasets successfully collected and usable for analysis. This is a feasibility outcome.
Time frame: Baseline, six-week, 10-week, and 18- week follow-ups and throughout the 6-week intervention period.
Box and Block Test (BBT) score
The gross manual dexterity and upper extremity coordination will be assessed through BBT, which involves transfer of blocks from one compartment of a box to the other within 60 seconds. The score is the number of blocks successfully transferred to the other side within 60 seconds.
Time frame: Baseline, six-week follow-up, and 10-week follow-up. Keeping a 18-week follow-up as an exploratory time point.
Modified Ashworth Scale (MAS) score
The increase in muscle tone will be assessed through MAS around the elbow and shoulder. MAS score ranges from 0 to 5. The MAS score reflects the severity of muscle spasticity.
Time frame: Baseline, six-week follow-up, and 10-week follow-up. Keeping a 18-week follow-up as an exploratory time point.
Wolf Motor Function Test (WMFT) score
Motor function will be assessed through WMFT, which evaluates both the time and quality of performance across 17 tasks that range from simple joint movements to complex functional activities (like lifting a can or folding a towel). Performance Time (sec) is measured, with a maximum time limit (usually 120 seconds). Functional Ability Scale rates the quality of movement, using a 6-point ordinal scale (0 = Does not attempt with the involved arm, 1 = Attempted but cannot complete task, 2 = Completes task with great difficulty or poor movement quality, 3 = Completes task with moderate difficulty or noticeable impairment, 4 = Completes task with minor difficulty or near-normal movement, 5 = Normal movement quality and speed). The WMFT score assesses upper extremity motor function.
Time frame: Baseline, six-week follow-up, and 10-week follow-up. Keeping a 18-week follow-up as an exploratory time point.
Plan to share: No
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