Biomarkers of Independent Walking Post-Stroke
- Conditions
- Gait, HemiplegicStroke, Acute
- Interventions
- Diagnostic Test: MRIDiagnostic Test: blood drawOther: Clinical assessments
- Registration Number
- NCT05004389
- Lead Sponsor
- University of Vermont
- Brief Summary
Prediction of walking recovery after stroke can inform patient-centered care and support discharge planning. The accuracy of current prediction models is limited, however, due to small study designs and narrow predictors assessed. The investigators propose a comprehensive evaluation of a novel combination of biomarkers to improve prediction of walking recovery and guide rehabilitation efforts after stroke. These include acute structural brain network disruption (utilizing MRI); blood biomarker levels (e.g., brain-derived neurotrophic factor and vascular endothelial growth factor); and clinical assessments of strength and mobility. The overall study objectives are to assess protocol feasibility and investigate relationships between select biomarkers and walking recovery to provide strong justification for a larger study on predictors of independent walking after stroke. The proposed objectives will be pursued through the following specific aims: 1) Assess feasibility of a larger study and develop methods for telehealth data collection; 2) Establish baseline levels of biomarkers and average change over time; and 3) Elucidate relationships between baseline levels of biomarkers and walking gains across time in persons after stroke. A longitudinal, observational study design will be utilized for this study. Thirty-five persons with acute (≤7 days) stroke will be recruited from the local medical center. Select inclusion criteria include presence of new lower limb weakness and assistance for walking; select exclusion criteria include cerebellar stroke or other neurological disorders such as Parkinson's Disease. Subjects will undergo clinical evaluation at week 1, 4, 9, 12, and 26 weeks post-stroke. MRI scans will occur within 12 days post-stroke and at 12 weeks post-stroke, and blood draws within 1 week, 1 to 2 weeks and at 12 weeks post-stroke. To assess feasibility the investigators will examine study processes, recruitment, resources, study management, and scientific assessment. To examine the role of acute clinical, neuroimaging, and physiological measures in predicting walking recovery, the investigators will examine relationships between these measures and walking outcome at 12-weeks post-stroke. The proposed research is expected to provide strong scientific support for future clinical trials designed to target therapies based on predicted functional potential. Such knowledge has the potential of enhancing mobility gains and patient independence following stroke.
- Detailed Description
The investigators will utilize a longitudinal, observational study design to investigate predictors of walking recovery post-stroke. Subjects will undergo clinical evaluation at week 1, 4, 9, 12, and 26 weeks after the initial onset of stroke symptoms; MRI scan within 12 days and at 12 weeks post-stroke; and blood draws at 1 week, 1 to 2 weeks and at 12 weeks post-stroke. Subjects will be recruited from the University of Vermont Medical Center (UVMMC), with a goal sample of 35 patients (accounts for 15% attrition). Subjects will provide written consent before participation.
Aim 1: Assess feasibility of a larger study and develop methods for telehealth data collection
Data Collection: To assess feasibility the investigators will examine study processes, recruitment, resources, study management, and scientific assessment.
Data Analyses: Feasibility questions will be examined using descriptive statistics and qualitative analyses. To ensure collection and dissemination of high quality data, the "CONSORT 2010 checklist of information to include when reporting a pilot or feasibility trial" will be used to guide data collection and analysis.
Aim 2: Establish baseline levels of biomarkers (clinical, neuroimaging, blood) and average change over time.
Experimental Protocol: Subjects will undergo baseline clinical assessment (within 1-week post-stroke), MRI scan (within 12 days post-stroke), and blood draw (within 1 week post-stroke). These same measures will be repeated 12 weeks after stroke (primary predictive outcome).
Data Analyses:
1. Establishing baseline levels of clinical measures, neuroimaging and blood biomarkers: To determine the variability in participants' walking ability/balance/strength, post-stroke preservation of sensorimotor connectivity, and acute changes in blood markers associated with immune response (IL-6, IL-10, cross-reacting protein, TNF alpha), neural function (BDNF), and blood vessel/ circulation (VEGF, matrix metalloproteinase, insulin like growth factor-1, cGP), descriptive statistics will be obtained. Results will be stratified by stroke characteristics and NIHSS score.
2. Quantifying change over time for clinical measures: defined as the average difference between 1-4-,9-,12-, and 26-week values. To examine change over time, the investigators will perform paired t-tests (or non-parametric equivalent) and effect size calculations on all outcome measures, using the 12 week post-stroke timepoint as the primary outcome. The investigators will also use the following minimal clinically important difference (MCID) or minimal detectable change (MDC) values to determine if observed statistical differences are clinically relevant: 0.16 m/s change in gait speed, 6-point change in Berg Balance Scale, and a change of three repetitions in 30 second Sit-To-Stand.
3. Quantifying change over time for neuroimaging and blood biomarkers: defined as the average difference between baseline and 12-week values. To examine change over time, the investigators will perform paired t-tests (or non-parametric equivalent) and effect size calculations.
4. Secondary analyses: will be performed with assistance and training from Core C (e.g., 5 dimensions spatial-temporal maps of walking biomechanics and/or muscle activation).
Aim 3: Elucidate relationships between baseline levels of biomarkers and walking gains across time in persons after stroke.
Experimental Protocol: Subjects will undergo the same experimental procedures as in Aims 1 and 2.
Data Analysis: To study the role of acute clinical, neuroimaging, and physiological measures in predicting recovery of independent walking post-stroke, the investigators will examine relationships between these measures and walking outcome as defined by the Functional Ambulation Category (FAC).
1. Identifying the time to regaining independent walking after stroke: defined as the time post-stroke (as measured at 1, 4, 9, 12, or 26 weeks post-stroke) at which a participant achieves a score of ≥4 on the FAC.
2. Quantifying the relationship between acute measures and walking outcome at 12 weeks post-stroke (primary predictive outcome): the relationship between clinical, MRI, and blood biomarkers and walking outcome at 12 weeks post-stroke (± independently walking) will be examined using logistic regression, correcting for potential confounders \[age, sex, stroke severity (NIHSS)\]. Secondary analyses will be performed by evaluating trends over time (repeated measures model).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 35
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Acute Stroke Clinical assessments Persons ≥ 18 years of age with acute (≤ 7 days) ischemic or intracerebral hemorrhagic stroke. Acute Stroke MRI Persons ≥ 18 years of age with acute (≤ 7 days) ischemic or intracerebral hemorrhagic stroke. Acute Stroke blood draw Persons ≥ 18 years of age with acute (≤ 7 days) ischemic or intracerebral hemorrhagic stroke.
- Primary Outcome Measures
Name Time Method Change in Functional Ambulation Category week 1, week 4, week 9, week 12, and week 26 s/p stroke Assessment of walking assistance
Change in blood markers - VEGF within week 1, at 1-2 weeks and at 12 weeks post-stroke serum VEGF
Change in diffusion tensor imaging within 12 days and at 12 weeks post-stroke fractional anisotropy and structural connectivity metrics
Change in blood markers - BDNF within week 1, at 1-2 weeks and at 12 weeks post-stroke serum BDNF
- Secondary Outcome Measures
Name Time Method Change in 3-meter walk test week 1, week 4, week 9, week 12, and week 26 s/p stroke Assessment of gait speed
Change in National Institutes of Health Stroke Scale within 72 hours and 1 week post-stroke Stroke severity assessment; scores range from 0 (min) to 42 (max), with higher values indicating greater stroke severity (worse outcome)
Change in Barthel Index week 12 and 26 s/p stroke Assessment of activities of daily living
Change in Modified Rankin Scale week 12 and 26 s/p stroke Assessment of level of disability; scores range from 0 (min) to 5 (max), with higher values indicating greater disability (worse outcome)
Mini-Mental Status Exam 1 week post-stroke Cognition
Change in Trunk Control Test week 1, week 4, week 9, week 12, and week 26 s/p stroke Assessment of trunk/postural control
Change in lower extremity muscle strength as assessed by Medical Research Council grades week 1, week 4, week 9, week 12, and week 26 s/p stroke Assessment of specific muscle strength; scores range from 0 (no muscle contraction) to 5 (normal power)
Change in Berg Balance Scale week 1, week 4, week 9, week 12, and week 26 s/p stroke Assessment of static/dynamic sitting and standing balance; scores range from 0 (min) to 56 (max), with higher values indicating better balance/outcome
Change in Motricity Index (lower limb portion) week 1 , week 4, week 9, week 12, and week 26 s/p stroke assessment of motor function/strength of the lower limbs
Change in Modified 30 second sit to stand week 1, week 4, week 9, week 12, and week 26 s/p stroke Assessment of lower limb power
Change in Fatigue Severity Scale week 1, week 4, week 9, week 12, and week 26 s/p stroke Assessment of fatigue level; scores range from 9 (min) to 63 (max), with higher values indicating greater fatigue severity (worse outcome)
Change in physical activity levels as assessed by the Physical Activity Vital Sign questionnaire week 12 and 26 post-stroke Assessment of physical activity levels; self-report of average number of days and minutes engaged in physical activity per week
Change in blood markers - IL-6 within week 1,at 1-2 weeks and at 12 weeks post-stroke IL-6
Change in blood markers - cGP within 1 week, at 1-2 weeks and at 12 weeks post-stroke cGP
Change in Opal sensor metric - gait week 1, week 4, week 9, week 12, and week 26 s/p stroke Assessment of spatiotemporal parameters of gait
Change in Opal sensor metric - posture week 1, week 4, week 9, week 12, and week 26 s/p stroke Assessment of postural sway
Change in blood markers - IL-10 within week 1,at 1-2 weeks and at 12 weeks post-stroke IL-10
Change in blood markers - C reactive protein within week 1 ,at 1-2 weeks and at 12 weeks post-stroke CRP
Change in blood markers - TNFalpha within week 1, at 1-2 weeks and at 12 weeks post-stroke TNFalpha
Change in blood markers - matrix metalloproteinase within week 1, at 1-2 weeks and at 12 weeks post-stroke MMP
Change in blood markers - insulin-like growth factor-1 within 1 week, at 1-2 weeks and at 12 weeks post-stroke IGF-1
Trial Locations
- Locations (1)
University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States