StrokeEarly Phase 1ENCMSNCT06666673
Effect of Neural Constraints on Movement in Stroke
A Early Phase 1 study testing Tizanidine in people with Stroke, run by Northwestern University at 1 site in United States.
Trial summary
This study investigates the effects of Tizanidine on the voluntary movement controls of the arms of participants who have had a stroke and have not had a stroke by measuring medication-induced changes in upper extremity kinematics, pupillometry, and brain activity. Tizanidine is approved by the U.S. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Stroke
- What is being tested?
- Tizanidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Aug 2024to 31 Jul 2029
- Phase
- Early Phase 1
- 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- History of unilateral supratentorial ischemic stroke that occurred at least six months prior to enrollment
- Age between 18-80
- Paresis confined to one side, with substantial motor impairment of the upper limb and some residual voluntary movement (Upper Extremity Fugl-Meyer Assessment in the range of 10-50/66)
- Ability to communicate, understand, and provide informed consent
- Ability to elevate their limb against gravity up to at least 75 degrees of shoulder flexion and to generate active elbow extension
- MRI compatible
- Intact skin on the hemiparetic arm
- Ability to sit for three hours.
Who cannot join
- Motor or sensory impairment in the non-affected limb (FMA<66, filament >3.6)
- Any brainstem and/or cerebellar lesion
- untreated cardiovascular disease
- History of neurologic disorder other than stroke that affects the arms
- Any acute or chronic painful condition in the upper extremities or spine, indicated by a score ≥5 on a 10-point visual analog scale
- Current use of a pacemaker
Show all 13Show fewer
- History of seizure
- Chemo denervation: botulinum toxin injection to any portion of the paretic upper extremity within the last 6 months, or phenol/alcohol injections <12 months before participation
- Flexion contractures larger than 30 degrees in the elbow, wrist, metacarpophalangeal joints (MCP) and interphalangeal joints (IP) after stretching for 15 minutes
- Current participation in any experimental rehabilitation or drug studies
- Individuals with any known contraindications to Tizanidine or currently taking Tizanidine; - concurrent use of medications known to suppress central nervous system activity
- pregnant women or women who are nursing.
- Additionally, each participant will be asked to provide a list of their current medications and a medical screening questionnaire will be sent to their primary physician. Each participant's list of medications will be reviewed for possible interactions with the study drugs and, at the study physician's advice, will be excluded from the study or asked to withhold medications when applicable. A full list of potential drug interactions can be seen in "Medication Interactions", but concisely includes the following: medications with dopaminergic, serotonergic, or noradrenergic actions; central nervous system (CNS) depressants; antihypertensive/ antiarrhythmic agents; and hormonal medications/contraceptives.
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
Northwestern University, Dept. of PTHMS 645 N Michigan Ave, Suite 1100
Chicago, Illinois, 60611
Julius Dewald, PhD, 312-908-6788, j-dewald@northwestern.edu
Riegele Arceo, 312-908-0847, riegele.arceo@northwestern.edu
About this study
This study investigates the effects of Tizanidine on the voluntary movement controls of the arms of participants who have had a stroke and have not had a stroke by measuring medication-induced changes in upper extremity kinematics, pupillometry, and brain activity. Tizanidine is approved by the U.S. Food and Drug Administration. Understanding how different areas of the brain are involved in movement impairments may help rehabilitation efforts and assist in restoring healthy movement in individuals who have had a stroke.
Read the detailed description
Sixty-four individuals with stroke will be recruited. Efforts will be made to recruit the same participants for each protocol. A REDCap database for this study will be setup to manage every step involved in the protocol.
The experiment uses a two-arm, cross-over, double-blinded, pre-test-post-test, randomized controlled design. After confirming eligibility, all enrolled participants will be scheduled for one anatomic brain MRI data collection and 6 arm/ hand experiments: 2 for each aim, one with TIZ and the other with placebo. All experiments will take place on separate days at least one week apart. During each of the experimental sessions, the participant will complete the protocol both before and 1.5 hours after administration of either TIZ or a placebo. The order of using TIZ or a placebo will be double-blinded and randomized to balance the FMA of the participants who receive the TIZ or placebo during their first session. In Aim 1, individuals will perform various isometric tasks with their paretic upper limb while high-density surface electromyography is used to estimate the behavior of their motor units. In Aim 2, individuals will perform isometric shoulder abduction with their cortical activity estimated with electroencephalography and their muscle activity recorded with electromyography. In Aim 3, individuals will be placed in a novel robotic device and asked to produce various shoulder abduction torques while either being perturbed by the device to elicit stretch reflexes or asked to perform reaching and hand-opening tasks. For all aims, joint torque and surface electromyographic data will be obtained from each participant before and 1.5 hours after administration of placebo or Tizanidine. Additionally, electroencephalographic data will be obtained during the second aim and joint kinematics will be obtained in the third aim. In all aims, participants will be seated in a Biodex chair (System 3 ProTM; Shirley, New York, USA) with their paretic limb interfaced to a novel haptic device (NACT-3D, Plaisier et. al., 2023) to measure and manipulate the forces/torques experienced by the participant. Throughout each session, straps will be placed across the chest and waist to prevent unwanted movement. The total time from enrollment to completion of participants is expected to be 8-12 weeks, during which participants will be instructed to keep performing routine daily activities.
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 PIs, IRB, NICHD, and other oversight organizations in accordance with their requirements. In the annual AE summary, the PIs Report will state that they have reviewed all AE reports.
- Conditions
- Stroke
- Being tested
- Tizanidine, Placebo
- Keywords
- Neurotransmitters, flexion synergy, brain plasticity, tizanidine, stroke, motor control, spasticity
- Medical subject headings
- Stroke, Muscle Spasticity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TizanidineDrug
Also called Zanaflex®
Tizanidine (TIZ) (Zanaflex®) is a centrally acting noradrenergic α-2 agonist and a ligand of I3 (non-I1/I2) imidazoline receptors. It is currently indicated for the management of spasticity.
PlaceboDrug
Administered as control
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | One lactose pill will be administered as a control. Receives: Drug: Placebo |
| Drug Probe | Active comparator | 4 mg Tizanidine Receives: Drug: Tizanidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brace Height
Brace height quantifies the amplification in motor unit discharge rate generated by PICs. Brace height is sensitive to the level of neuromodulatory drive received by motoneurons.
Measured: Before and 1.5 hours after administration of TIZ
Cortico-muscular-coherence in beta band
Cortico-muscular coherence (CMC) is a commonly used method to measure the synchronized activity between cortex and muscles. Specifically, betaband CMC has been reported to be linked to the use of corticospinal tract.
Measured: Before and 1.5 hours after administration of TIZ
Difference in reaching distance under shoulder abduction load
The difference in reaching distance under shoulder abduction (SABD) load measures the strength of flexion synergy.
Measured: Before and 1.5 hours after administration of TIZ
Reflexive electromyograph activity prior to movement
Reflexive electromyograph (EMG) activity will be calculated as the difference between perturbation-induced EMG amplitude and baseline EMG, averaged during three-time windows 1) before the perturbation -100- 0 ms pre-perturbation; 2) 25 - 75 ms (shortlatency stretch reflex) and 2) 75 - 125 ms (long latency stretch reflex) after the perturbation onset. Perturbations occur at rest before the onset of a regular ballistic reaching trial. EMG is then normalized by the maximal EMG of the corresponding muscle.
Measured: Before and 1.5 hours after administration of TIZ
Secondary outcomes (5)
Delta-F
Delta-F quantifies hysteresis (i.e., prolongation, or persistence) in motor unit firing induced by persistent inward currents (PICs). Delta-F is less selective to the level of neuromodulatory drive, but also accounts for inhibitory synaptic inputs to motoneurons.
Measured: Before and 1.5 hours after administration of TIZ
Cortico-muscular-coherence in alpha band
Alpha-band cortico-muscular-coherence (CMC) has been reported to be linked to the use of cortico-reticulospinal tract. A decreased use of cortico-reticulospinal tract will indirectly reflect an increased use of corticospinal tract, when the require motor task is still performed successfully.
Measured: Before and 1.5 hours after administration of TIZ
Cortical Laterality Index (LI)
LI measures the relatively higher (close to 1) or lower (close to -1) cortical activity between the lesioned vs non-lesioned motor cortices. An increase in LI indicates a shift of cortical activity towards the lesioned motor cortices, and thus reflecting an increased use of corticospinal tract. Minimum value is -1 and maximum value is 1. Higher scores indicate increased use of corticospinal tract.
Measured: Before and 1.5 hours after administration of TIZ
Difference in Hand hexagon area under SABD load
Hand hexagon area (HHA), i.e. the polygon created by connecting the five fingers of the hand with the base of the palm together in a plane, measures hand opening ability. The difference in HHA under SABD load also measures the strength of flexion synergy, but more distally. The investigators hypothesize that the difference under load will become less following tizanidine administration.
Measured: Before and 1.5 hours after administration of TIZ
Reflexive EMG activity during movement
The investigators will calculate the reflexive EMG activity as in Hypothesis 3.2, but with the perturbation occurring during the onset of a ballistic reach.
Measured: Before and 1.5 hours after administration of TIZ
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2024
- Study start23 Aug 2024
- Primary completion30 Jun 2029 (estimated)
- Study completion31 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Jun Yao, Northwestern University
- Investigators
- Julius Dewald, DPT, PhD, Principal investigator, Northwestern UniversityJun Yao, PhD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06666673
- Sponsor's protocol ID
- STU00223059
- Other IDs
- 2R01HD039343-16
- Acronym
- ENCMS
- Status last verified
- Sep 2026
- First submitted
- 10 Oct 2024
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Neural Constraints on Movement in Stroke
- ClinicalTrials.gov ID
- NCT06666673
- Acronym / sponsor ID
- ENCMS / STU00223059
- Conditions
- Stroke
- Keywords
- Neurotransmitters, flexion synergy, brain plasticity, tizanidine, stroke, motor control, spasticity
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 23 Aug 2024 (actual)
- Primary completion
- 30 Jun 2029 (estimated)
- Study completion
- 31 Jul 2029 (estimated)
- First posted
- 30 Oct 2024 (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.
This study investigates the effects of Tizanidine on the voluntary movement controls of the arms of participants who have had a stroke and have not had a stroke by measuring medication-induced changes in upper extremity kinematics, pupillometry, and brain activity. Tizanidine is approved by the U.S. Food and Drug Administration. Understanding how different areas of the brain are involved in movement impairments may help rehabilitation efforts and assist in restoring healthy movement in individuals who have had a stroke.
Detailed description
Sixty-four individuals with stroke will be recruited. Efforts will be made to recruit the same participants for each protocol. A REDCap database for this study will be setup to manage every step involved in the protocol.
The experiment uses a two-arm, cross-over, double-blinded, pre-test-post-test, randomized controlled design. After confirming eligibility, all enrolled participants will be scheduled for one anatomic brain MRI data collection and 6 arm/ hand experiments: 2 for each aim, one with TIZ and the other with placebo. All experiments will take place on separate days at least one week apart. During each of the experimental sessions, the participant will complete the protocol both before and 1.5 hours after administration of either TIZ or a placebo. The order of using TIZ or a placebo will be double-blinded and randomized to balance the FMA of the participants who receive the TIZ or placebo during their first session. In Aim 1, individuals will perform various isometric tasks with their paretic upper limb while high-density surface electromyography is used to estimate the behavior of their motor units. In Aim 2, individuals will perform isometric shoulder abduction with their cortical activity estimated with electroencephalography and their muscle activity recorded with electromyography. In Aim 3, individuals will be placed in a novel robotic device and asked to produce various shoulder abduction torques while either being perturbed by the device to elicit stretch reflexes or asked to perform reaching and hand-opening tasks. For all aims, joint torque and surface electromyographic data will be obtained from each participant before and 1.5 hours after administration of placebo or Tizanidine. Additionally, electroencephalographic data will be obtained during the second aim and joint kinematics will be obtained in the third aim. In all aims, participants will be seated in a Biodex chair (System 3 ProTM; Shirley, New York, USA) with their paretic limb interfaced to a novel haptic device (NACT-3D, Plaisier et. al., 2023) to measure and manipulate the forces/torques experienced by the participant. Throughout each session, straps will be placed across the chest and waist to prevent unwanted movement. The total time from enrollment to completion of participants is expected to be 8-12 weeks, during which participants will be instructed to keep performing routine daily activities.
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 PIs, IRB, NICHD, and other oversight organizations in accordance with their requirements. In the annual AE summary, the PIs Report will state that they have reviewed all AE reports.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboOne lactose pill will be administered as a control. |
| Drug Probe | Active comparator | Drug: Tizanidine4 mg Tizanidine |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- History of unilateral supratentorial ischemic stroke that occurred at least six months prior to enrollment
- Age between 18-80
- Paresis confined to one side, with substantial motor impairment of the upper limb and some residual voluntary movement (Upper Extremity Fugl-Meyer Assessment in the range of 10-50/66)
- Ability to communicate, understand, and provide informed consent
- Ability to elevate their limb against gravity up to at least 75 degrees of shoulder flexion and to generate active elbow extension
Key exclusion criteria (13 listed)
- Motor or sensory impairment in the non-affected limb (FMA<66, filament >3.6)
- Any brainstem and/or cerebellar lesion
- untreated cardiovascular disease
- History of neurologic disorder other than stroke that affects the arms
- Any acute or chronic painful condition in the upper extremities or spine, indicated by a score ≥5 on a 10-point visual analog scale
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 |
|---|---|---|
| TizanidineAlso: Zanaflex®Tizanidine (TIZ) (Zanaflex®) is a centrally acting noradrenergic α-2 agonist and a ligand of I3 (non-I1/I2) imidazoline receptors. It is currently indicated for the management of spasticity. | Drug | Drug Probe |
| PlaceboAdministered as control | Drug | Placebo |
Primary outcome
Brace Height
Time frame: Before and 1.5 hours after administration of TIZ
Brace height quantifies the amplification in motor unit discharge rate generated by PICs. Brace height is sensitive to the level of neuromodulatory drive received by motoneurons.
Cortico-muscular-coherence in beta band
Time frame: Before and 1.5 hours after administration of TIZ
Cortico-muscular coherence (CMC) is a commonly used method to measure the synchronized activity between cortex and muscles. Specifically, betaband CMC has been reported to be linked to the use of corticospinal tract.
Difference in reaching distance under shoulder abduction load
Time frame: Before and 1.5 hours after administration of TIZ
The difference in reaching distance under shoulder abduction (SABD) load measures the strength of flexion synergy.
Reflexive electromyograph activity prior to movement
Time frame: Before and 1.5 hours after administration of TIZ
Reflexive electromyograph (EMG) activity will be calculated as the difference between perturbation-induced EMG amplitude and baseline EMG, averaged during three-time windows 1) before the perturbation -100- 0 ms pre-perturbation; 2) 25 - 75 ms (shortlatency stretch reflex) and 2) 75 - 125 ms (long latency stretch reflex) after the perturbation onset. Perturbations occur at rest before the onset of a regular ballistic reaching trial. EMG is then normalized by the maximal EMG of the corresponding muscle.
5 secondary outcomes
Delta-F
Time frame: Before and 1.5 hours after administration of TIZ
Cortico-muscular-coherence in alpha band
Time frame: Before and 1.5 hours after administration of TIZ
Cortical Laterality Index (LI)
Time frame: Before and 1.5 hours after administration of TIZ
Difference in Hand hexagon area under SABD load
Time frame: Before and 1.5 hours after administration of TIZ
Reflexive EMG activity during movement
Time frame: Before and 1.5 hours after administration of TIZ
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 5 Oct 2026.
- 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.
Julius Dewald, DPT, PhD principal investigator
Northwestern University
Jun Yao, PhD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Tizanidine in people with Stroke, run by Northwestern University 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 8 inclusion and 13 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 5 Oct 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Riegele Arceo (3129080847, riegele.arceo@northwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brace Height (time frame: Before and 1.5 hours after administration of TIZ). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Oct 2026.