Stroke, IschemicREACT+NMESNCT06127602
The REACTplusNMES Trial: A Double-blinded RCT
A study testing Reactive balance training with Neuromuscular Electrical Stimulation and Reactive balance training without Neuromuscular Electrical Stimulation in people with Stroke, Ischemic and Stroke Hemorrhagic, run by University of Illinois at Chicago at 1 site in United States.
Trial summary
The aim of this study is to compare the effectiveness of 6-weeks of reactive balance training (REACT) with and without neuromuscular electrical stimulation (NMES) to paretic lower limb muscles on biomechanical, clinical, neuromuscular and neuroplastic outcomes of reactive balance control. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Stroke, Ischemic, Stroke Hemorrhagic, Stroke, Cerebrovascular
- What is being tested?
- Reactive balance training with Neuromuscular Electrical Stimulation and Reactive balance training without Neuromuscular Electrical Stimulation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2024to 31 May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age group: 18-90 years.
- Presence of hemiparesis.
- Onset of stroke (> 6 months).
- Ability to walk at least for 2 minutes on the treadmill with or without ankle foot orthosis.
- Can understand and communicate in English.
- Cognitively and behaviorally capable of complying with the regimen (Mini-Mental State Examination > 25/30).
- No history or recent use (i.e., past 6 weeks) of any Neuromuscular electrical stimulation device to leg muscles during walking (e.g., Bioness, Walkaide).
Who cannot join
- Subjects will not proceed with the test if any of the following occurs at baseline measurement: 1) HR > 85% of age-predicted maximal heart rate (HRmax) (HRmax = 220 - age), 2) systolic blood pressure (SBP) > 165 mmHg and/or diastolic blood pressure (DBP) > 110 mmHg during rest, or 3) oxygen saturation (measured by pulse oximeter) < 95% during rest.
- Body weight of more than 250 lbs.
- Spasticity (Ashworth scale > 2).
- Loss of protective sensations on the paretic leg (indicated by inability to perceive the 5.07/10 g on Semmes-Weinstein Monofilament) or inability to feel the NMES.
- Severe osteoporosis (indicated by T score < -2)
- Cognitive impairment (indicated by Mini-Mental State Exam score<25)
- Global Aphasia (indicated by <71% on the Mississippi Aphasia Screening Test).
- Subjects with Chedoke McMaster Leg Assessment Scale score (> 4).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Illinois at Chicago
Chicago, Illinois, 60612
Tanvi Bhatt, PhD, 3123554443, tbhatt6@uic.edu
Rudri Purohit, MS, 312-413-9772, rpuroh2@uic.edu
About this study
Official title: NeuroMuscular Electrical Stimulation to Facilitate Perturbation-based REACtive Balance Training for Fall Risk Reduction Post-stroke: The REACTplusNMES Trial
The aim of this study is to compare the effectiveness of 6-weeks of reactive balance training (REACT) with and without neuromuscular electrical stimulation (NMES) to paretic lower limb muscles on biomechanical, clinical, neuromuscular and neuroplastic outcomes of reactive balance control. This project is a Phase-I study and incorporates a double-blinded, randomized controlled trial design.
Methods: Forty-six individuals with chronic stroke will be recruited and screened for determining their eligibility for the study. Once enrolled, they will be randomized into either of the two groups: intervention group (23 participants) and control group (23 participants). Both groups will undergo series of pre-training assessments which includes a postural disturbance in the form of a slip- or trip-like perturbations and walking tests in laboratory environment. After the pre-training assessment, individuals will undergo 6-weeks of training (2 hour per session, 2 sessions per week). The intervention group will receive NMES with the REACT training and the control group will receive ShamNMES. NMES will be applied to the different muscle groups of the paretic lower limb using an advanced software which is able to synchronize muscle activation with the time of perturbation onset and according to the phases of gait. After training, both groups will again be tested on all the assessments performed pre training.
This study will help us understand the immediate therapeutic and mechanistic effects of REACT+NMES and inform stroke rehabilitation research and clinical practice. Our study will provide foundational evidence for future use of NMES to implement clinically applicable neuromodulation adjuvants to reactive balance training, which could be leveraged for designing more effective future interventions for fall-risk reduction.
Read the detailed description
1.0 Background/Scientific Rationale Interventions such as conventional balance and exercise training constitute a major part of stroke rehabilitation and improve volitional balance control and gait in people with chronic hemiparetic stroke (PwCHS). However, they seldom target reactive balance (compensatory postural responses such as stepping) that forms the first line of defense while recovering from a balance loss. Reactive balance in PwCHS is affected by deficits in perturbation-evoked neuromuscular and biomechanical responses especially during gait. Further, previous research has shown that stability and adaptions to repeated perturbations is more affected on paretic compared to non-paretic limb. Thus, paretic limb deficits are postulated to be key contributors of falls in ambulatory PwCHS. Perturbation-based reactive balance training (REACT) is widely recognized as an intervention that reduces falls by improving fall-resisting skills. In the past five years, there is a 3-fold increase in perturbation training research in PwCHS (mostly low impairment). Thus, limited evidence exists for PwCHS with severe motor impairment who might not show similar tolerance or learning abilities.
Complementing REACT with interventions known to facilitate paretic limb performance and motor learning (i.e., neuromuscular electrical stimulation, NMES) can improve therapeutic effects of REACT and hence its clinical translation for PwCHS and other populations that could benefit from fall-risk reduction. While it is established that REACT programs and NMES can induce motor learning in behavioral variables, there is limited evidence on neuroplastic changes and exact neural mechanisms underlying these behavioral changes (especially during REACT). Similar to the precision medicine approach, modifiable causative factors, contributors, and mediators to falls must be targeted when designing effective falls prevention interventions that reduce training times and/or facilitate the inclusion of persons with high impairment.
This project aims to describe whether a specific pattern of lower limb muscle stimulation could modify the recovery response after an unexpected perturbation in the form of a slip and/or trip in individuals with stroke. Also, this study aims to examine the effectiveness of 6-weeks of reactive balance training (REACT) with and without neuromuscular electrical stimulation (NMES) to paretic lower limb muscles on biomechanical, clinical, neuromuscular and neuroplastic outcomes of reactive balance control.
2.0 Objectives/Aims
The specific aims of this study are below:
Aim 1: To examine effects of synchronous REACT+NMES on reactive balance control and clinical outcomes among people with chronic stroke with moderate to severe motor impairment.
H1.1: REACT+NMES will induce greater improvement in biomechanical outcomes of reactive balance (reactive stability, limb support) resulting in fewer laboratory falls post-training than REACT+ShamNMES (at 6 weeks).
H1.2: The improvements in reactive balance control in REACT+NMES will translate to greater improvement in clinical outcomes of balance (mini-BEST test), gait (10m walk test) and falls-efficacy (Activities specific Balance Confidence scores) than REACT. H1.3: The improvements in reactive balance control will also translate to reduced falls during overground gait-slips after REACT+NMES.
Aim 2: To examine neuromuscular and neuroplastic effects of REACT+NMES in PwCHS with moderate to severe motor impairment.
H2.1. REACT+NMES will induce greater neuromuscular (muscle synergy #s and activations) and neuroplastic (perturbation evoked potentials- PEPs) changes post-training than REACT (at 6 weeks).
H2.2: Baseline PEP amplitude and training-induced neuroplastic changes in PEP's will correlate with the training-induced improvements in biomechanical and neuromuscular responses.
3.0 Research Design This study trial employs a two-arm, double-blinded, randomized controlled trial (RCT) design This study will examine efficacy and feasibility of REACT-NMES intervention compared to REACT+ShamNMES among PwCHS with moderate to severe motor impairment (Aim 1 and 2) A sample size of 46 chronic stroke survivors will be enrolled, undergo initial screening and pre-training assessment, and then randomized into two groups (intervention and control). Next, both groups will undergo 6-weeks of in-lab reactive balance training (2x/week, total 12 sessions). After training, participants in both groups will undergo a post-training assessment, which will include all the tests performed in the pre-training assessment.
Study overview: All participants will undergo the following procedures.
- Session 1 (Week 1): Initial screening (2 hours)
- Session 2 (Week 2): Pre-test (total 4 hours)
- Session 3-15 (Week 3-8): Training sessions (2 hours/session, 2 times/week for 6 weeks) (total: 24 hours)
- Session 16 (Week 9): Post-test (total 4 hours)
- Being tested
- Reactive balance training with Neuromuscular Electrical Stimulation, Reactive balance training without Neuromuscular Electrical Stimulation
- Keywords
- Reactive balance, Falls, Perturbation training, NMES, FES, Stroke, Fall prevention, Neuroplastic, Neuromuscular
- Medical subject headings
- Ischemic Stroke, Hemorrhagic Stroke, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reactive balance training with Neuromuscular Electrical StimulationBehavioural
REACT-NMES group: The ActiveStep treadmill will be used to deliver slips during all sessions. Each subject will experience three levels of perturbations over 12 sessions (24 slips/session) in progressive ascending way. On the first week, subjects will start with the lowest displacement level (6 cm) and move up to the next level (12 cm) by week 2 if they have < 5 falls out of 8 slips at the previous level. By week 3, subjects are expected to move to level 3 (24 cm) and train at that for weeks 3 to 6. If subjects don't move up a level, training will continue at the lower level. NMES will be delivered to the vastus lateralis synchronously with the perturbation, which will always occur 50 ms after slip-onset and last for 450 ms including the period between liftoff to touchdown of the first compensatory step.
Reactive balance training without Neuromuscular Electrical StimulationBehavioural
REACT group: The REACT group will undergo the same reactive balance training (in terms of type, dosage: intensity, frequency) as the REACT-NMES group. The only difference will be that the REACT group will receive ShamNMES for same time after the compensatory step touchdown. The ActiveStep treadmill will be used to deliver slips during all sessions. Each subject will experience three levels of perturbations over 12 sessions (24 slips/session) in progressive ascending way. On the first week, subjects will start with the lowest displacement level (6 cm) and move up to the next level (12 cm) by week 2 if they have < 5 falls out of 8 slips at the previous level. By week 3, subjects are expected to move to level 3 (24 cm) and train at that for weeks 3 to 6. If subjects don't move up a level, training will continue at the lower level.
| Study group | Role | What they receive |
|---|---|---|
| REACT-NMES: Intervention condition | Experimental | The REACT-NMES group will undergo 6 weeks of reactive balance training with NMES involving 12 one-hour sessions (twice a week). Each session will begin with NMES parameter setup where the current amplitude will be customized to individual "maximal tolerable" levels for a strong yet comfortable experience. NMES settings will include moderate to high intensity (30-50mA) and low frequency (20-45Hz) to target motor nerve thresholds. The REACT-NMES group will wear a footswitch on their paretic shoe for triggering the slips during walking and for NMES synchronization. NMES will be delivered to the paretic limb quadriceps muscles for 500 milliseconds after slip onset. Receives: Behavioral: Reactive balance training with Neuromuscular Electrical Stimulation |
| REACT: Control condition | Active comparator | The REACT group will undergo 6 weeks involving 12 one-hour sessions (twice a week) of reactive balance training with ShamNMES. To prevent psychological bias and unblinding, sub-sensory stimulation will be used. ShamNMES will employ low intensity (0-10mA) and high frequency (50-100Hz), staying 20% below the sensory nerve threshold without inducing muscle contraction. The REACT group will wear a footswitch on their paretic shoe for triggering the slips during walking and for ShamNMES synchronization. ShamNMES (control) will be delivered after compensatory step touchdown to avoid interference with balance recovery. Receives: Behavioral: Reactive balance training without Neuromuscular Electrical Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Falls
A fall will be detected when the force exerted through the safety-harness load cell exceeds 30% of a person's body weight and verified with video analysis. Otherwise, the trial will be a balance recovery. Higher percentages indicate more falls.
Measured: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Change in Reactive Stability
Reactive stability (dimensionless) will be measured at the time point of compensatory limb touchdown after slipping.
Stability will be calculated as the shortest distance from the COM state to the backward balance loss threshold. The instantaneous COM state is determined by its position and velocity (computed from filtered marker data) relative to the BOS, normalized respectively to foot length and the square root of the product of gravitational acceleration and body height. Higher values indicate better reactive stability.
Measured: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Change in Proactive Stability
Proactive stability (dimensionless) will be measured at the time point of slipping limb touchdown i.e., before slipping.
Stability will be calculated as the shortest distance from the COM state to the backward balance loss threshold. The instantaneous COM state is determined by its position and velocity (computed from filtered marker data) relative to the BOS, normalized respectively to foot length and the square root of the product of gravitational acceleration and body height. Higher values indicate better proactive stability.
Measured: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Change in Vertical Limb support
Vertical limb support (dimensionless) is quantified by the quotient of hip vertical velocity to its height (VZhip/ Zhip). Zhip will be obtained as the vertical distance of the bilateral hip midpoint to the surface of the platform and its vertical velocity (VZhip), as the first-order differentiation of hip height. Its positive direction is upward. Higher values indicate better vertical limb support.
Measured: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Change in Muscle synergies
To assess the muscular synergies, electromyography sensors will be applied to four muscle groups on both lower limbs. The muscle groups include tibialis anterior, gastrocnemius, quadriceps and hamstring group of muscles. Higher values indicate more muscle synergies.
Measured: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Change in Perturbation-evoked potentials
Data from different midline electroencephalographic (EEG) channels overlying lower limb frontal, sensorimotor and parietal regions will be used to extract the perturbation-evoked potentials (P1, N1, P2 and N2) to assess their spatio-temporal parameter (amplitude: microvolts, latency: seconds)
Measured: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Change in time-frequency power
Data from different midline electroencephalographic channels overlying lower limb frontal, sensorimotor, and parietal regions will be used to extract the alpha, beta, theta, and gamma power (decibels). Higher values indicate more frequency power.
Measured: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Secondary outcomes (3)
Change in Margin of Stability
Margins of stability (dimensionless) will be computed by determining the distance between the center of mass (COM) position and a person's base of support through the three-dimensional motion analysis system. Higher values indicate a better margin of stability.
Measured: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Change in Step length
Compensatory step length (meters) is the distance from slipping heel to compensatory heel at the instance of first limb touchdown post-slipping. Negative values indicated a backward compensatory step relative to the slipping limb, with greater negative values indicated a longer step and vice versa.
Measured: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Change in Step initiation time
Compensatory step initiation time (seconds) is the time taken for liftoff of the compensatory limb after perturbation onset. Lower values indicated better performance i.e., lesser time required to initiate a compensatory step following slip onset.
Measured: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2023
- Study start1 Mar 2024
- Primary completion1 Mar 2027 (estimated)
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Stroke, IschemicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blinded Randomized Controlled Trial
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Illinois at Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tanvi Bhatt, University of Illinois at Chicago
- Investigators
- Tanvi Bhatt, Principal investigator, University of Illinois at Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06127602
- Sponsor's protocol ID
- 2023-1233
- Acronym
- REACT+NMES
- Status last verified
- Jul 2026
- First submitted
- 25 Oct 2023
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kesar T, Chou LW, Binder-Macleod SA. Effects of stimulation frequency versus pulse duration modulation on muscle fatigue. J Electromyogr Kinesiol. 2008 Aug;18(4):662-71. doi: 10.1016/j.jelekin.2007.01.001. Epub 2007 Feb 21.
PubMed 17317219Varas-Diaz G, Bhatt T. Application of neuromuscular electrical stimulation on the support limb during reactive balance control in persons with stroke: a pilot study. Exp Brain Res. 2021 Dec;239(12):3635-3647. doi: 10.1007/s00221-021-06209-2. Epub 2021 Oct 5.
PubMed 34609544Pereira S, Mehta S, McIntyre A, Lobo L, Teasell RW. Functional electrical stimulation for improving gait in persons with chronic stroke. Top Stroke Rehabil. 2012 Nov-Dec;19(6):491-8. doi: 10.1310/tsr1906-491.
PubMed 23192714Dusane S, Bhatt T. Effect of Multisession Progressive Gait-Slip Training on Fall-Resisting Skills of People with Chronic Stroke: Examining Motor Adaptation in Reactive Stability. Brain Sci. 2021 Jul 7;11(7):894. doi: 10.3390/brainsci11070894.
PubMed 34356128Kottink AI, Oostendorp LJ, Buurke JH, Nene AV, Hermens HJ, IJzerman MJ. The orthotic effect of functional electrical stimulation on the improvement of walking in stroke patients with a dropped foot: a systematic review. Artif Organs. 2004 Jun;28(6):577-86. doi: 10.1111/j.1525-1594.2004.07310.x.
PubMed 15153151
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NeuroMuscular Electrical Stimulation to Facilitate Perturbation-based REACtive Balance Training for Fall Risk Reduction Post-stroke: The REACTplusNMES Trial
- ClinicalTrials.gov ID
- NCT06127602
- Acronym / sponsor ID
- REACT+NMES / 2023-1233
- Keywords
- Reactive balance, Falls, Perturbation training, NMES, FES, Stroke, Fall prevention, Neuroplastic
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- University of Illinois at ChicagoUniversity, hospital or other
- Study start
- 1 Mar 2024 (actual)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 13 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to compare the effectiveness of 6-weeks of reactive balance training (REACT) with and without neuromuscular electrical stimulation (NMES) to paretic lower limb muscles on biomechanical, clinical, neuromuscular and neuroplastic outcomes of reactive balance control. This project is a Phase-I study and incorporates a double-blinded, randomized controlled trial design.
Methods: Forty-six individuals with chronic stroke will be recruited and screened for determining their eligibility for the study. Once enrolled, they will be randomized into either of the two groups: intervention group (23 participants) and control group (23 participants). Both groups will undergo series of pre-training assessments which includes a postural disturbance in the form of a slip- or trip-like perturbations and walking tests in laboratory environment. After the pre-training assessment, individuals will undergo 6-weeks of training (2 hour per session, 2 sessions per week). The intervention group will receive NMES with the REACT training and the control group will receive ShamNMES. NMES will be applied to the different muscle groups of the paretic lower limb using an advanced software which is able to synchronize muscle activation with the time of perturbation onset and according to the phases of gait. After training, both groups will again be tested on all the assessments performed pre training.
This study will help us understand the immediate therapeutic and mechanistic effects of REACT+NMES and inform stroke rehabilitation research and clinical practice. Our study will provide foundational evidence for future use of NMES to implement clinically applicable neuromodulation adjuvants to reactive balance training, which could be leveraged for designing more effective future interventions for fall-risk reduction.
Detailed description
1.0 Background/Scientific Rationale Interventions such as conventional balance and exercise training constitute a major part of stroke rehabilitation and improve volitional balance control and gait in people with chronic hemiparetic stroke (PwCHS). However, they seldom target reactive balance (compensatory postural responses such as stepping) that forms the first line of defense while recovering from a balance loss. Reactive balance in PwCHS is affected by deficits in perturbation-evoked neuromuscular and biomechanical responses especially during gait. Further, previous research has shown that stability and adaptions to repeated perturbations is more affected on paretic compared to non-paretic limb. Thus, paretic limb deficits are postulated to be key contributors of falls in ambulatory PwCHS. Perturbation-based reactive balance training (REACT) is widely recognized as an intervention that reduces falls by improving fall-resisting skills. In the past five years, there is a 3-fold increase in perturbation training research in PwCHS (mostly low impairment). Thus, limited evidence exists for PwCHS with severe motor impairment who might not show similar tolerance or learning abilities.
Complementing REACT with interventions known to facilitate paretic limb performance and motor learning (i.e., neuromuscular electrical stimulation, NMES) can improve therapeutic effects of REACT and hence its clinical translation for PwCHS and other populations that could benefit from fall-risk reduction. While it is established that REACT programs and NMES can induce motor learning in behavioral variables, there is limited evidence on neuroplastic changes and exact neural mechanisms underlying these behavioral changes (especially during REACT). Similar to the precision medicine approach, modifiable causative factors, contributors, and mediators to falls must be targeted when designing effective falls prevention interventions that reduce training times and/or facilitate the inclusion of persons with high impairment.
This project aims to describe whether a specific pattern of lower limb muscle stimulation could modify the recovery response after an unexpected perturbation in the form of a slip and/or trip in individuals with stroke. Also, this study aims to examine the effectiveness of 6-weeks of reactive balance training (REACT) with and without neuromuscular electrical stimulation (NMES) to paretic lower limb muscles on biomechanical, clinical, neuromuscular and neuroplastic outcomes of reactive balance control.
2.0 Objectives/Aims
The specific aims of this study are below:
Aim 1: To examine effects of synchronous REACT+NMES on reactive balance control and clinical outcomes among people with chronic stroke with moderate to severe motor impairment.
H1.1: REACT+NMES will induce greater improvement in biomechanical outcomes of reactive balance (reactive stability, limb support) resulting in fewer laboratory falls post-training than REACT+ShamNMES (at 6 weeks).
H1.2: The improvements in reactive balance control in REACT+NMES will translate to greater improvement in clinical outcomes of balance (mini-BEST test), gait (10m walk test) and falls-efficacy (Activities specific Balance Confidence scores) than REACT. H1.3: The improvements in reactive balance control will also translate to reduced falls during overground gait-slips after REACT+NMES.
Aim 2: To examine neuromuscular and neuroplastic effects of REACT+NMES in PwCHS with moderate to severe motor impairment.
H2.1. REACT+NMES will induce greater neuromuscular (muscle synergy #s and activations) and neuroplastic (perturbation evoked potentials- PEPs) changes post-training than REACT (at 6 weeks).
H2.2: Baseline PEP amplitude and training-induced neuroplastic changes in PEP's will correlate with the training-induced improvements in biomechanical and neuromuscular responses.
3.0 Research Design This study trial employs a two-arm, double-blinded, randomized controlled trial (RCT) design This study will examine efficacy and feasibility of REACT-NMES intervention compared to REACT+ShamNMES among PwCHS with moderate to severe motor impairment (Aim 1 and 2) A sample size of 46 chronic stroke survivors will be enrolled, undergo initial screening and pre-training assessment, and then randomized into two groups (intervention and control). Next, both groups will undergo 6-weeks of in-lab reactive balance training (2x/week, total 12 sessions). After training, participants in both groups will undergo a post-training assessment, which will include all the tests performed in the pre-training assessment.
Study overview: All participants will undergo the following procedures.
- Session 1 (Week 1): Initial screening (2 hours)
- Session 2 (Week 2): Pre-test (total 4 hours)
- Session 3-15 (Week 3-8): Training sessions (2 hours/session, 2 times/week for 6 weeks) (total: 24 hours)
- Session 16 (Week 9): Post-test (total 4 hours)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blinded Randomized Controlled Trial
| Arm | Type | Receives |
|---|---|---|
| REACT-NMES: Intervention condition | Experimental | Behavioral: Reactive balance training with Neuromuscular Electrical StimulationThe REACT-NMES group will undergo 6 weeks of reactive balance training with NMES involving 12 one-hour sessions (twice a week). Each session will begin with NMES parameter setup where the current amplitude will be customized to individual "maximal tolerable" levels for a strong yet comfortable experience. NMES settings will include moderate to high intensity (30-50mA) and low frequency (20-45Hz) to target motor nerve thresholds. The REACT-NMES group will wear a footswitch on their paretic shoe for triggering the slips during walking and for NMES synchronization. NMES will be delivered to the paretic limb quadriceps muscles for 500 milliseconds after slip onset. |
| REACT: Control condition | Active comparator | Behavioral: Reactive balance training without Neuromuscular Electrical StimulationThe REACT group will undergo 6 weeks involving 12 one-hour sessions (twice a week) of reactive balance training with ShamNMES. To prevent psychological bias and unblinding, sub-sensory stimulation will be used. ShamNMES will employ low intensity (0-10mA) and high frequency (50-100Hz), staying 20% below the sensory nerve threshold without inducing muscle contraction. The REACT group will wear a footswitch on their paretic shoe for triggering the slips during walking and for ShamNMES synchronization. ShamNMES (control) will be delivered after compensatory step touchdown to avoid interference with balance recovery. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age group: 18-90 years.
- Presence of hemiparesis.
- Onset of stroke (> 6 months).
- Ability to walk at least for 2 minutes on the treadmill with or without ankle foot orthosis.
- Can understand and communicate in English.
Key exclusion criteria (8 listed)
- Subjects will not proceed with the test if any of the following occurs at baseline measurement: 1) HR > 85% of age-predicted maximal heart rate (HRmax) (HRmax = 220 - age), 2) systolic blood pressure (SBP) > 165 mmHg and/or diastolic blood pressure (DBP) > 110 mmHg during rest, or 3) oxygen saturation (measured by pulse oximeter) < 95% during rest.
- Body weight of more than 250 lbs.
- Spasticity (Ashworth scale > 2).
- Loss of protective sensations on the paretic leg (indicated by inability to perceive the 5.07/10 g on Semmes-Weinstein Monofilament) or inability to feel the NMES.
- Severe osteoporosis (indicated by T score < -2)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Reactive balance training with Neuromuscular Electrical StimulationREACT-NMES group: The ActiveStep treadmill will be used to deliver slips during all sessions. Each subject will experience three levels of perturbations over 12 sessions (24 slips/session) in progressive ascending way. On the first week, subjects will start with the lowest displacement level (6 cm) and move up to the next level (12 cm) by week 2 if they have < 5 falls out of 8 slips at the previous level. By week 3, subjects are expected to move to level 3 (24 cm) and train at that for weeks 3 to 6. If subjects don't move up a level, training will continue at the lower level. NMES will be delivered to the vastus lateralis synchronously with the perturbation, which will always occur 50 ms after slip-onset and last for 450 ms including the period between liftoff to touchdown of the first compensatory step. | Behavioural | REACT-NMES: Intervention condition |
| Reactive balance training without Neuromuscular Electrical StimulationREACT group: The REACT group will undergo the same reactive balance training (in terms of type, dosage: intensity, frequency) as the REACT-NMES group. The only difference will be that the REACT group will receive ShamNMES for same time after the compensatory step touchdown. The ActiveStep treadmill will be used to deliver slips during all sessions. Each subject will experience three levels of perturbations over 12 sessions (24 slips/session) in progressive ascending way. On the first week, subjects will start with the lowest displacement level (6 cm) and move up to the next level (12 cm) by week 2 if they have < 5 falls out of 8 slips at the previous level. By week 3, subjects are expected to move to level 3 (24 cm) and train at that for weeks 3 to 6. If subjects don't move up a level, training will continue at the lower level. | Behavioural | REACT: Control condition |
Primary outcome
Change in Falls
Time frame: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
A fall will be detected when the force exerted through the safety-harness load cell exceeds 30% of a person's body weight and verified with video analysis. Otherwise, the trial will be a balance recovery. Higher percentages indicate more falls.
Change in Reactive Stability
Time frame: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Reactive stability (dimensionless) will be measured at the time point of compensatory limb touchdown after slipping. Stability will be calculated as the shortest distance from the COM state to the backward balance loss threshold. The instantaneous COM state is determined by its position and velocity (computed from filtered marker data) relative to the BOS, normalized respectively to foot length and the square root of the product of gravitational acceleration and body height. Higher values indicate better reactive stability.
Change in Proactive Stability
Time frame: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Proactive stability (dimensionless) will be measured at the time point of slipping limb touchdown i.e., before slipping. Stability will be calculated as the shortest distance from the COM state to the backward balance loss threshold. The instantaneous COM state is determined by its position and velocity (computed from filtered marker data) relative to the BOS, normalized respectively to foot length and the square root of the product of gravitational acceleration and body height. Higher values indicate better proactive stability.
Change in Vertical Limb support
Time frame: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Vertical limb support (dimensionless) is quantified by the quotient of hip vertical velocity to its height (VZhip/ Zhip). Zhip will be obtained as the vertical distance of the bilateral hip midpoint to the surface of the platform and its vertical velocity (VZhip), as the first-order differentiation of hip height. Its positive direction is upward. Higher values indicate better vertical limb support.
Change in Muscle synergies
Time frame: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
To assess the muscular synergies, electromyography sensors will be applied to four muscle groups on both lower limbs. The muscle groups include tibialis anterior, gastrocnemius, quadriceps and hamstring group of muscles. Higher values indicate more muscle synergies.
Change in Perturbation-evoked potentials
Time frame: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Data from different midline electroencephalographic (EEG) channels overlying lower limb frontal, sensorimotor and parietal regions will be used to extract the perturbation-evoked potentials (P1, N1, P2 and N2) to assess their spatio-temporal parameter (amplitude: microvolts, latency: seconds)
Change in time-frequency power
Time frame: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Data from different midline electroencephalographic channels overlying lower limb frontal, sensorimotor, and parietal regions will be used to extract the alpha, beta, theta, and gamma power (decibels). Higher values indicate more frequency power.
3 secondary outcomes
Change in Margin of Stability
Time frame: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Change in Step length
Time frame: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Change in Step initiation time
Time frame: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
- Background: PubMed 17317219Kesar T, Chou LW, Binder-Macleod SA. Effects of stimulation frequency versus pulse duration modulation on muscle fatigue. J Electromyogr Kinesiol. 2008 Aug;18(4):662-71. doi: 10.1016/j.jelekin.2007.01.001. Epub 2007 Feb 21.
- Results publication: PubMed 34609544Varas-Diaz G, Bhatt T. Application of neuromuscular electrical stimulation on the support limb during reactive balance control in persons with stroke: a pilot study. Exp Brain Res. 2021 Dec;239(12):3635-3647. doi: 10.1007/s00221-021-06209-2. Epub 2021 Oct 5.
- Results publication: PubMed 23192714Pereira S, Mehta S, McIntyre A, Lobo L, Teasell RW. Functional electrical stimulation for improving gait in persons with chronic stroke. Top Stroke Rehabil. 2012 Nov-Dec;19(6):491-8. doi: 10.1310/tsr1906-491.
- Results publication: PubMed 34356128Dusane S, Bhatt T. Effect of Multisession Progressive Gait-Slip Training on Fall-Resisting Skills of People with Chronic Stroke: Examining Motor Adaptation in Reactive Stability. Brain Sci. 2021 Jul 7;11(7):894. doi: 10.3390/brainsci11070894.
- Results publication: PubMed 15153151Kottink AI, Oostendorp LJ, Buurke JH, Nene AV, Hermens HJ, IJzerman MJ. The orthotic effect of functional electrical stimulation on the improvement of walking in stroke patients with a dropped foot: a systematic review. Artif Organs. 2004 Jun;28(6):577-86. doi: 10.1111/j.1525-1594.2004.07310.x.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tanvi Bhatt principal investigator
University of Illinois at Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Reactive balance training with Neuromuscular Electrical Stimulation and Reactive balance training without Neuromuscular Electrical Stimulation in people with Stroke, Ischemic and Stroke Hemorrhagic, run by University of Illinois at Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rudri Purohit, MS (312-413-9772, rpuroh2@uic.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Falls (time frame: Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06127602, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026; AzTrials last refreshed its copy on 26 Oct 2026.