Effect of Neural Constraints on Movement in Stroke
ConditionStroke
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-80
SponsorNorthwestern University
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Crossover
Treatments tested in this trial
Tizanidine
DrugTizanidine (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.
Placebo
DrugAdministered as control
Treatment groups
64 Participants
are divided into 2 treatment groupsGroup A: PlaceboPlacebo comparator 1 intervention
Group B: Drug ProbeActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Before and 1.5 hours after administration of TIZ2
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.
Time frame
Before and 1.5 hours after administration of TIZ3
Difference in reaching distance under shoulder abduction load
The difference in reaching distance under shoulder abduction (SABD) load measures the strength of flexion synergy.
Time frame
Before and 1.5 hours after administration of TIZ4
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.
Time frame
Before and 1.5 hours after administration of TIZSecondary outcomes
1
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.
Time frame
Before and 1.5 hours after administration of TIZ2
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.
Time frame
Before and 1.5 hours after administration of TIZ3
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.
Time frame
Before and 1.5 hours after administration of TIZ4
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.
Time frame
Before and 1.5 hours after administration of TIZSponsors and contacts
Click on the lead sponsor to view all of their trials.
Northwestern University
Lead sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborator
Source ClinicalTrials.gov