Biomarkers of Independent Walking Post-Stroke

NCT ID: NCT05004389

Last Updated: 2023-03-14

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 35 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-12-02
• Study Completion Date: 2023-05-31

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).

Conditions

Stroke, Acute; Gait, Hemiplegic

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Acute Stroke

Persons ≥ 18 years of age with acute (≤ 7 days) ischemic or intracerebral hemorrhagic stroke.

MRI

Intervention Type: DIAGNOSTIC_TEST

white matter integrity and brain structural connectivity metrics

blood draw

Intervention Type: DIAGNOSTIC_TEST

post-stroke serum/plasma levels of BDNF, VEGF, IL-6, IL-10, CRP, TNFalpha, MMPs, IGF-1, cGP

Clinical assessments

Intervention Type: OTHER

measures of strength, balance, and mobility

Interventions

MRI

white matter integrity and brain structural connectivity metrics

Intervention Type: DIAGNOSTIC_TEST

blood draw

post-stroke serum/plasma levels of BDNF, VEGF, IL-6, IL-10, CRP, TNFalpha, MMPs, IGF-1, cGP

Intervention Type: DIAGNOSTIC_TEST

Clinical assessments

measures of strength, balance, and mobility

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Inclusion criteria: 1) individuals with acute (≤ 7 days) ischemic or intra-cerebral hemorrhagic stroke; 2) ≥18 years of age; 3) presence of new lower limb weakness (less than 5/5 on manual muscle testing) on one side of the body or notation of weakness by MD or PT) on one side of the body; 4) unable to walk or requires supervision or assistance for walking.

Exclusion criteria: 1) cerebellar or bilateral stroke; 2) requirement for supervision or physical assistance to walk prior to admission; 3) other neurological disorders such as Parkinson's Disease or Multiple Sclerosis, 4) severe hearing impairment, 5) blindness, 6) actively receiving treatment for cancer, 7) not expected to survive for duration of the study, and 8) diagnosis of current clinical definition of active COVID-19.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of General Medical Sciences (NIGMS)

NIH

Sponsor Role: collaborator

University of Vermont

OTHER

Sponsor Role: lead

Responsible Party

Denise Peters

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Denise Peters, DPT, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Vermont

Locations

University of Vermont Medical Center

Burlington, Vermont, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Denise Peters, DPT, PhD

Role: CONTACT

denise.peters@med.uvm.edu

802-656-1709

Facility Contacts

Swapna Research Coordinator

Role: primary

swapna.balakrishnan@uvm.edu

Other Identifiers

P20GM135007

Identifier Type: NIH

Identifier Source: secondary_id

View Link

00000696

Identifier Type: -

Identifier Source: org_study_id