VERIFY will validate biomarkers of upper extremity (UE) motor outcome in the acute ischemic stroke window for immediate use in clinical trials, and explore these biomarkers in acute intracerebral hemorrhage. The central hypothesis is that patients have different UE outcomes depending on corticomotor system (CMS) function, measured as motor evoked potential (MEP) status with TMS, and on CMS structure, measured as acute lesion load with MRI. VERIFY will create the first multicenter, large-scale, prospective dataset of clinical, TMS, and MRI measures in the acute stroke time window.
Trial Design and Outcomes:
VERIFY is a multicenter, biomarker validation study of upper extremity motor outcome. VERIFY will validate biomarkers in the acute ischemic stroke window of upper extremity (UE) motor outcome, for immediate use in clinical trials. The central hypothesis is that patients have different UE outcomes depending on CMS function, measured as motor evoked potential (MEP) status via TMS, and on CMS structure, measured as CST lesion load via MRI. This biomarker validation study will be performed at as many as 35 acute care hospitals in the United States participating in the NIH StrokeNet. VERIFY builds on previous work showing that MEP status and MRI prognostic biomarkers distinguish between patients who will have different UE motor outcomes. However, these studies have important limitations. First, baseline measures were sometimes collected up to 2 weeks after stroke onset, which does not meet the goal of stratifying patients during the acute stroke admission. Second, most studies were performed at a single center, often with advanced TMS expertise, and with limited sample size. External validation with a large sample across a range of stroke centers is needed. Third, prior studies have used a range of TMS and MRI techniques, but a standardized protocol needs to be tested. VERIFY is designed to overcome these limitations. Objectives:
Primary Aim 1: To externally validate the relationships that TMS and MRI biomarkers of CMS integrity acquired ≤ 7 days after stroke have with 90-day UE motor impairment outcome after ischemic stroke.
Primary Aim 2: To externally validate the PREP2 prediction tool used ≤ 7 days after stroke to predict 90-day UE functional outcome for individual participants with ischemic stroke.
Exploratory 1: To derive and internally validate multivariable prediction tools, using TMS and MRI CMS biomarkers as well as baseline clinical factors, to predict 90-day patient-reported UE use and global functional outcome in individual participants.
Exploratory 2: To collect outcomes in other domains of recovery to generate hypotheses that allow consideration of future ancillary studies and future directions from this rich dataset.
- Aim 1: UE-Fugl Meyer (UE-FM) Score, as a continuous scale at 90 days
- Aim 2: Action Research Arm Test (ARAT), categorized as excellent, good, limited, or poor at 90 days
Exploratory Endpoints, all at 90 Days
- Motor Activity Log (MAL), categorized as 0-2 vs. 3-5 at 90 days
- Modified Rankin Score (mRS) level (0-6) at 90 days
Study Sponsor and Chair:
Pooja Khatri, MD MSc (Lead), University of Cincinnati
Achala Vagal, MD MS, University of Cincinnati
Steven C. Cramer, MD MSc, University of California Los Angeles
Cathy M. Stinear, PhD, University of Auckland
NIH National Institute of Neurological Disorders and Stroke (NINDS) - 1U01NS120910-01
NIH StrokeNet National Coordinating Center at the University of Cincinnati
NIH StrokeNet National Data Management Center at Medical University of South Carolina
US FDA IDE # G200291
For More Information:
University of Cincinnati
260 Stetson St, ML 0525
Cincinnati, OH. 45219