Effect of Neural Constraints on Movement in Stroke

NCT06666673 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: STU002230592R01HD039343-16
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Stroke

Keywords

Neurotransmitters; flexion synergy; brain plasticity; tizanidine; stroke; motor control; spasticity

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Before and 1.5 hours after administration of TIZ

Secondary Outcomes (5)

• Delta-F

  Before and 1.5 hours after administration of TIZ

• Cortico-muscular-coherence in alpha band

  Before and 1.5 hours after administration of TIZ

• Cortical Laterality Index (LI)

  Before and 1.5 hours after administration of TIZ

• Difference in Hand hexagon area under SABD load

  Before and 1.5 hours after administration of TIZ

• Reflexive EMG activity during movement

  Before and 1.5 hours after administration of TIZ

Study Arms (2)

Placebo

PLACEBO COMPARATOR

One lactose pill will be administered as a control.

Drug: Placebo

Drug Probe

ACTIVE COMPARATOR

8 mg Tizanidine

Drug: Tizanidine

Interventions

Tizanidine DRUG

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.

Also known as: Zanaflex®

Drug Probe

Placebo DRUG

Administered as control

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 15-45/66, Chedoke McMaster Stroke Assessment Hand section \<=4)
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Northwestern University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Northwestern University, Dept. of PTHMS 645 N Michigan Ave, Suite 1100

Chicago, Illinois, 60611, United States

RECRUITING

MeSH Terms

Conditions

Stroke; Muscle Spasticity

Interventions

tizanidine

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Julius Dewald, DPT, PhD

  Northwestern University

  PRINCIPAL INVESTIGATOR

• Jun Yao, PhD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Riegele Arceo

CONTACT

3129080847; riegele.arceo@northwestern.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 10, 2024
• First Posted: October 30, 2024
• Study Start: August 23, 2024
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): July 31, 2029
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)