The REACTplusNMES Trial: A Double-blinded RCT

NCT06127602 | Recruiting DMC

• 1 other identifier: 2023-1233
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Stroke, Ischemic; Stroke Hemorrhagic; Stroke, Cerebrovascular

Keywords

Reactive balance; Falls; Perturbation training; NMES; FES; Stroke; Fall prevention; Neuroplastic; Neuromuscular

Outcome Measures

Primary Outcomes (7)

• 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.

  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.

  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.

  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.

  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.

  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)

  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.

  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

  Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)

• Change in Step length

  Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)

• Change in Step initiation time

  Pre-training (during week 2 i.e., Session 2), Post-training (during week 9 i.e., Session 16)

Study Arms (2)

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.

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.

Behavioral: Reactive balance training without Neuromuscular Electrical Stimulation

Interventions

Reactive balance training with Neuromuscular Electrical Stimulation BEHAVIORAL

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.

REACT-NMES: Intervention condition

Reactive balance training without Neuromuscular Electrical Stimulation BEHAVIORAL

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.

REACT: Control condition

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

RECRUITING

Related Publications (5)

• 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.

  PMID: 17317219 BACKGROUND

• Varas-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.

  PMID: 34609544 RESULT

• Pereira 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.

  PMID: 23192714 RESULT

• Dusane 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.

  PMID: 34356128 RESULT

• Kottink 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.

  PMID: 15153151 RESULT

MeSH Terms

Conditions

Ischemic Stroke; Hemorrhagic Stroke; Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Tanvi Bhatt

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rudri Purohit, MS

CONTACT

312-413-9772; rpuroh2@uic.edu

Swaranka Deshmukh, MS

CONTACT

312-355-3988; sdeshm9@uic.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Subjects will be blinded to group existence and assignment and outcome assessors will be blinded to group assignment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Model Details: Double-blinded Randomized Controlled Trial

Study Record Dates

• First Submitted: October 25, 2023
• First Posted: November 13, 2023
• Study Start: March 1, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: August 6, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)