Motor rECovery witH eArly imagiNg In STroke

Stroke Clinical Trial

— MECHANIST  

Official title:

MECHANIST: Motor rECovery witH eArly imagiNg In STroke

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04165616
• Other study ID #: STU00210349
• Secondary ID: R01NS105759
• Status: Recruiting
• Start date: June 21, 2022
• Est. completion date: May 2025

Study information

• Verified date: March 2024
• Source: Northwestern University
• Contact: Michael D Ellis, PT, DPT
• Phone: 312-503-4435
• Email: m-ellis[@]northwestern.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study will contribute to the field of stroke rehabilitation research by expanding the investigator's understanding of the neural mechanisms responsible for the development and expression of abnormal flexion synergy, a primary movement impairment due to stroke. The study will longitudinally evaluate motor tract morphology and motor impairment/function in an attempt to develop early neuroimaging-based predictors of the development of flexion synergy and its impact on reaching and hand recovery (6 month). The study will utilize quantitative motor testing (kinematics and kinetics) to measure motor impairment and reaching and hand function. Both neuroimaging and quantitative motor testing will be conducted within 96 hours-, 2 weeks-, 3 months-, and 6 months-post stroke. The knowledge gained by this study will provide crucial structural and functional neuroimaging evidence that demonstrates the timeline of progressive ipsi- and contralesional motor pathway (including bulbospinal pathways) changes and the associated development of flexion synergy that grossly impacts reaching and hand function in individuals with moderate to severe stroke.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: May 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Stroke within the middle cerebral artery distribution based on brain MRI done within 48 hours of admission

2. 18 to 85 years old

3. Isolated motor deficits (hemiparesis) without significant aphasia, visual disturbances, or neglect based on the following scores on the NIH Stroke Scale: 1a (level of consciousness) = 0- Alert; keenly responsive. 1b (LOC questions) = 0- Asked month and age; Answers both correctly. 1c (LOC commands) = 0- Asked to open/close eyes, grasp/release hand; Performs both correctly. 2 (Best Gaze) = 0- Horizontal eye movements; Normal. 5 (Motor Arm) = 1, 2, 3, or 4- Arm placed at 90 (sitting) or 45 (supine), Drift, Some effort, No effort against gravity, or No movement. 7 (Limb Ataxia) = 0- Finger-nose-finger or heel-shin test; Absent. 8 (Sensory) = 0 or 1- Pin prick; Normal or Mild-to-moderate sensory loss. 9 (Best Language) = 0 or 1- Describe picture; No or Mild-to-moderate Aphasia. 11 (Extinction and Inattention) = 0 or 1- No abnormality or Inattention to one modality.

Exclusion Criteria:

1. Premorbid disability or sensorimotor impairment

2. Comorbidity medically contraindicating the administration of subsequent MRI scanning and motor assessments

3. Pain or hypersensitivity limiting motor assessment

4. Limb edema limiting motor assessment

Related Conditions & MeSH terms

• Stroke

Locations

Country	Name	City	State
United States	Department of Physical Therapy and Human Movement Sciences	Chicago	Illinois
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Shirley Ryan AbilityLab	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Northwestern University	National Institute of Neurological Disorders and Stroke (NINDS), Shirley Ryan AbilityLab

Country where clinical trial is conducted

United States, 

References & Publications (3)

Ellis MD, Carmona C, Drogos J, Dewald JPA. Progressive Abduction Loading Therapy with Horizontal-Plane Viscous Resistance Targeting Weakness and Flexion Synergy to Treat Upper Limb Function in Chronic Hemiparetic Stroke: A Randomized Clinical Trial. Front Neurol. 2018 Feb 19;9:71. doi: 10.3389/fneur.2018.00071. eCollection 2018. — View Citation

Karbasforoushan H, Cohen-Adad J, Dewald JPA. Brainstem and spinal cord MRI identifies altered sensorimotor pathways post-stroke. Nat Commun. 2019 Aug 6;10(1):3524. doi: 10.1038/s41467-019-11244-3. Erratum In: Nat Commun. 2020 Jul 6;11(1):3433. — View Citation

McPherson JG, Chen A, Ellis MD, Yao J, Heckman CJ, Dewald JPA. Progressive recruitment of contralesional cortico-reticulospinal pathways drives motor impairment post stroke. J Physiol. 2018 Apr 1;596(7):1211-1225. doi: 10.1113/JP274968. Epub 2018 Feb 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in fractional anisotropy	Fractional anisotropy is a quantitative measure of fiber density, axonal diameter, and myelination in the corticofugal, corticoreticulospinal, and corticorubrospinal tracts derived from the diffusion tensor imaging dataset.	Change in fractional anisotropy will be modeled over 4 time points (48-96 hours-, 2 weeks-, 3 months-, and 6 months post-stroke).
Primary	Change in complexity	Complexity (alpha) is an index of the non-Gaussian diffusion dynamics within the corticofugal, corticoreticulospinal, and corticorubrospinal tracts derived from the diffusion tensor imaging dataset.	Change in complexity will be modeled over 4 time points (48-96 hours-, 2 weeks-, 3 months-, and 6 months post-stroke).
Primary	Change in mean diffusivity	Mean diffusivity is a measure of neural tract integrity quantifying the rotationally invariant magnitude of water diffusion within neural tissue defined by the 3-dimensional diffusion tensor.	Change in mean diffusivity will be modeled over 4 time points (48-96 hours-, 2 weeks-, 3 months-, and 6 months post-stroke).
Primary	Change in radial diffusivity	Radial diffusivity is a measure of neural membrane integrity quantifying the average of the two small-axis values of water diffusion within neural tissue defined by the 3-dimensional diffusion tensor.	Change in radial diffusivity will be modeled over 4 time points (48-96 hours-, 2 weeks-, 3 months-, and 6 months post-stroke).
Primary	Change in axial diffusivity	Axial diffusivity is a measure of neural tract direction quantifying the long-axis value of water diffusion within neural tissue defined by the 3-dimensional diffusion tensor.	Change in axial diffusivity will be modeled over 4 time points (48-96 hours-, 2 weeks-, 3 months-, and 6 months post-stroke).
Primary	Change in maximum reaching distance	Quantitative evaluation of reaching accounting for the expression of both flexion synergy and weakness by calculating distance from reaching kinematics data during ballistic outward reaches against various abduction loads.	Change in maximum reaching distance will be modeled over 4 time points (48-96 hours-, 2 weeks-, 3 months-, and 6 months post-stroke).
Primary	Change in maximum hand aperture	Quantitative evaluation of hand opening accounting for the expression of both flexion synergy and weakness by calculating the area of a pentagon formed by the finger tips from hand kinematics data obtained at various abduction loads.	Change in maximum hand aperture will be modeled over 4 time points (48-96 hours-, 2 weeks-, 3 months-, and 6 months post-stroke).
Primary	Change in maximum grasp force	Quantitative evaluation of hand closing accounting for the expression of both flexion synergy and weakness by calculating the mean surface grasp force of the hand at various abduction loads.	Change in maximum grasp force will be modeled over 4 time points (48-96 hours-, 2 weeks-, 3 months-, and 6 months post-stroke).
Primary	Predictive capacity of diffusor tensor imaging (DTI) for 6-month reaching and hand performance	Changes in structural morphology measured acutely will be evaluated as early predictors for chronic reaching and hand performance. Receiver operating characteristic (ROC) curve analysis will be used to evaluate the discrimination potential of each acute imaging measure in predicting chronic moderate versus severe motor impairment for each of the reaching and hand performance measures.	Changes in structural morphology from 48 hours to 2-weeks post-stroke will be evaluated as early predictors for the 6-month reaching and hand performance outcomes including ROC curve analysis.
Primary	Relationship between DTI and quantitative motor testing	The relationship between each structural morphology metric and each quantitative motor testing metric will be evaluated.	Relationships between metrics will be modeled over 4 time points (48-96 hours-, 2 weeks-, 3 months-, and 6 months post-stroke).
Secondary	Change in Fugl-Meyer Motor Assessment	Qualitative and clinical assessment of general motor impairment of arm following stroke. The scale evaluates movement impairment of the arm through observation. The scale ranges from 0-66 points with 66 indicating the best score.	Change in Fugl-Meyer Motor Assessment will be modeled over 4 time points (48-96 hours-, 2 weeks-, 3 months-, and 6 months post-stroke).
Secondary	Change in Action Research Arm Test	Qualitative and clinical assessment of activity limitation (function) of the arm following stroke. The scale focusses on reaching, grasping, and releasing objects of various sizes. The scale ranges from 0-57 with 57 indicating the best score.	Change in Action Research Arm Test will be modeled over 4 time points (48-96 hours-, 2 weeks-, 3 months-, and 6 months post-stroke).
Secondary	Change in Stroke Impact Scale	Structured interview to assess domains of the ICF (International Classification of Functioning, Disability and Health) in individuals following stroke. The domains include self-reported physical problems, memory and thinking, control of emotions, communication, daily activities, home and community mobility, the affected hand, participation and life roles, and global recovery. Each domain score is transformed to a scale of 0-100 with 100 being the best score.	Change in Stroke Impact Scale will be modeled over 4 time points (48-96 hours-, 2 weeks-, 3 months-, and 6 months post-stroke).