Impaired Interlimb Coordination During Locomotion in Individuals With Chronic Stroke: Contributors and Effect on Walking Function

NCT07006818 | Recruiting

• 1 other identifier: UIC EXITO Pilot 2025
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Individuals with chronic stroke have long-term walking problems that limit community engagement and quality of life, lead to secondary disabilities, and increase healthcare costs and burden. These walking issues often persist despite rehabilitation. One novel target for stroke gait rehabilitation is interlimb coordination-the phase-dependent cyclical relation of the legs. Interlimb coordination is altered during walking after stroke, compromising walking stability, phase transitions, and responses to perturbation and contributing to motor compensation. It is unclear what neural pathways contribute to impaired interlimb coordination after stroke and what impact this has on walking-related outcomes. This proposal consists of two aims to address these issues, with the long-term goal of developing therapeutic interventions to improve interlimb coordination and walking after stroke. Aim 1 will identify which neural sources contribute to impaired interlimb coordination after stroke. During bilateral, cyclical recumbent stepping (analogue of walking), interlimb coordination will be assessed as relative leg phasing. During the task, transcranial magnetic stimulation and peripheral nerve stimulation will be applied to assess supraspinal, interhemispheric, spinal interneuronal, and sensory pathways. The relation of interlimb coordination with these outcomes will be assessed to determine potential contributors. Aim 2 will test the association between interlimb coordination and walking after stroke. Interlimb coordination will be quantified during split-belt treadmill walking, and associations with walking speed, endurance, mobility, independence, daily activity, quality of life, and community engagement will be tested. An additional exploratory aim will determine the effect of targeted neuromodulation on lower limb interlimb coordination. Electrical stimulation will be applied to three locations in a cross-over study: the primary motor cortex (supraspinal/interhemispheric), thoracolumbar spine (spinal interneuronal), and peripheral nerves (sensory).

Conditions

Stroke

Outcome Measures

Primary Outcomes (3)

• Corticomotor excitability

  Transcranial magnetic stimulation (TMS) will be used to measure change in contralateral and ipsilateral corticomotor excitability of the paretic tibialis anterior, medial gastrocnemius, rectus femoris, and biceps femoris. TMS will be applied at different intensities, and the response (motor evoked potential) is measured in the paretic TMS. Corticomotor excitability will be measured as the slope of the input output curve (intensity vs. response). Higher values represent greater corticomotor excitability.

  immediately before and after immediately after the intervention

• Cutaneous reflexes

  A train of 5 short duration (1 ms) electrical pulses at \~300 Hz will be applied to the cutaneous superficial peroneal nerve. These pulses elicit reflex responses in muscles throughout the leg (cutaneous reflexes). Amplitude of muscle activation during stimulation will be compared to periods without stimulation.

  immediately before and after immediately after the intervention

• H-reflexes

  1ms electrical pulses will be applied to the deep fibular (peroneal) nerve. Two evoked potentials (M-wave and H-reflex) in the muscle that will be recorded with electromyography (EMG). Stimulations will be applied at a variety of intensities ranging from 70% of H-reflex threshold up to 120% of M-Max. M and H input-output curves will be generated. We will extract the maximal H-reflex response at any intensity (H-max), calculate the H-max/M-max ratio, and determine the slope of the ascending portion of the H-reflex curve (determined with a sigmoidal function).

  immediately before and after immediately after the intervention

Secondary Outcomes (1)

• Interhemispheric inhibition

  immediately before and after immediately after the intervention

Study Arms (3)

Supraspinal direct current stimulation

EXPERIMENTAL

Participants will receive 2 mA direct current stimulation for 20 minutes, with the anode applied to the ipsilesional primary motor cortex and the cathode applied to the contralesional supraorbit.

Device: Direct current stimulation

Spinal direct current stimulation

EXPERIMENTAL

Participants will receive 2 mA direct current stimulation for 20 minutes, with the anode applied to the thoracic vertebra and the cathode applied to the non-paretic shoulder.

Device: Direct current stimulation

Sensory direct current stimulation

EXPERIMENTAL

Participants will receive 2 mA direct current stimulation for 20 minutes, with the anode and the cathode applied to the cutaneous superficial peroneal nerve.

Device: Direct current stimulation

Interventions

Direct current stimulation DEVICE

Direct current stimulation will be applied at 2 mA for 20 minutes.

Sensory direct current stimulation; Spinal direct current stimulation; Supraspinal direct current stimulation

Eligibility Criteria

• Age: 25 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 25 - 90 years of age
• Monohemispheric stroke
• Chronic phase (\> 6 months post stroke)
• Ability to walk for at least 6 minutes at a self-selected comfortable speed

You may not qualify if:

• Lesions affecting the brainstem or cerebellum
• Other neurological disorders
• Current botox treatments for the lower limb
• Significant cognitive or communication impairment
• Previous adverse reaction to TMS
• Skull abnormalities or fractures
• Concussion within the prior 6 months
• Unexplained, recurring headaches
• Implanted cardiac pacemaker
• Metal implants in the head or face
• History of seizures or epilepsy
• Use of medications that could increase risk of seizure
• Current pregnancy
• Skin hypersensitivity at any sites of stimulation, including the scalp, thoracolumbar spine, and peripheral limbs
• History of contact dermatitis at any of the sites of stimulation

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

RECRUITING

MeSH Terms

Conditions

Stroke

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Central Study Contacts

Brice T Cleland, PhD

CONTACT

3129969056; bcleland@uic.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Visiting Research Assistant Professor

Study Record Dates

• First Submitted: May 27, 2025
• First Posted: June 5, 2025
• Study Start: September 15, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: December 5, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: All shared data will be made available at latest by the time of associated publication or at the end of the performance period, whichever comes first. As permitted by the relevant repositories, data will be made available in perpetuity, but at minimum for 10 years.
• Access Criteria: All data described above will be shared on UIC INDIGO and UIC Research Data Glacier, university institutional and data repositories. All shared data will be accessible via persistent unique identifiers (Digital Object Identifier \[DOI\]). DOIs will be referenced in any related publications.

Locations

US (1)