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NCT05338697Recruiting

Validation of Early Prognostic Data for Recovery Outcome After Stroke for Future, Higher Yield Trials

University of Cincinnati

Start Date

6/18/2022

Completion Date

10/1/2027

Summary

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. VERIFY will create the first multicenter, large-scale, prospective dataset of clinical, transmagnetic stimulation (TMS), and MRI measures in the acute stroke time window.

Detailed Description

Currently, 7 million US stroke survivors have significant disability, more than half with residual motor deficits. Motor function, particularly of the upper extremity (UE), is critical for regaining independence after stroke. UE function largely depends on integrity of motor cortex and its descending fibers, collectively termed the corticomotor system (CMS). Validated, clinically relevant biomarkers that identify biologically distinct patient subgroups are critically needed, particularly for the often affected and functionally important CMS. Their absence is a major obstacle to developing and personalizing new recovery therapies, especially in the early days post stroke. Presence or absence of motor evoked potential (MEP) responses to TMS and extent of MRI-measured acute lesion load involving corticospinal tract (CST) are ready for formal validation. Also, the Predict Recovery Potential (PREP)-2 prediction tool, which sequentially combines acute clinical information and MEP status, is primed for multi-site validation. The central objective is to validate the most biologically relevant and primed biomarkers of 90-day UE motor outcomes after ischemic stroke in the first large-scale, prospective, acute dataset of clinical, TMS, and MRI measures. The central hypothesis is that patients have different UE outcomes depending on CMS function measured with TMS, and on CST injury measured with MRI. The specific aims are: 1. to externally validate the relationships that TMS and MRI biomarkers of CMS integrity have with 90-day UE motor impairment outcome and 2. to externally validate the PREP2 prediction tool to predict 90- day UE functional outcome. The study will also explore these biomarkers in acute intracerebral hemorrhage. The study will comprehensively measure UE outcomes 90 days post-stroke in three domains of motor performance -impairment, function, and use - identified by the World Health Organization International Classification of Functioning, Disability and Health. By establishing biomarkers for use in the acute stroke period to identify patient subgroups with distinct 90-day outcomes, the study will improve the efficiency of stroke recovery trials and inform rehabilitation decision-making. Sample Size: up to 657 participants with complete biomarker data enrolled at up to 45 sites. Trial Status: VERIFY received formal FDA IDE approval in November 2020 and received NIH funding in September 2021. Participating sites from the United States have been identified, and the study is now enrolling eligible participants.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: 1. Age 18 years or older 2. Unilateral symptomatic stroke due to ischemia. (Note: Bilateral acute stroke is permitted if the stroke that is contralateral to the index stroke is asymptomatic). 3. Motor deficits in the acutely affected UE, defined as a Shoulder Abduction and Finger Extension (SAFE) score ≤ 8 out of 10 points20,61 (i.e., excluding full or nearly full motor strength in both shoulder abduction and finger extension) within 48 to 96 hours of stroke onset (or time last known well). a. Please note that, if significant imbalance is observed in SAFE score or MEP+ rates, the enrollment threshold for SAFE score may be updated with a formal study memo. 4. Provision of signed and dated informed consent form within 24 to 96 hours of stroke onset, (or time last known well). Note: Participant is considered "enrolled" upon starting TMS (at least one stimulation is delivered) or starting study-specific MRI pulse sequence (at least one MRI beep occurs) 5. Stated willingness to comply with all study procedures and availability for the duration of the study, including Day 90 visit which must occur in-person. 6. Fluent in study approved languages (i.e., English or Spanish) Exclusion Criteria: 1. UE injury or conditions on paretic side that limited use prior to the stroke 2. Legally blind 3. Dense sensory loss on paretic side indicated by a score of 2 on NIHSS sensory item 4. Unable to abduct the shoulder or extend the fingers of the non-paretic UE on verbal command 5. Isolated cerebellar stroke 6. Symptomatic stroke in any location within 30 days prior to index stroke. 7. Co-enrollment in a trial of an intervention targeting the incident stroke (acute treatment or rehabilitation/recovery intervention) after baseline assessments for VERIFY are initiated 8. Known or expected inability to maintain follow-up with study procedures through 90 days 9. Cognitive or communication impairment precluding informed consent by the participant. 10. Major medical, neurological, or psychiatric condition that would substantially affect functional status 11. Non-cerebrovascular diagnosis associated with unlikely survival at 90 days 12. Pregnancy 13. Contraindication to noncontrast MRI (certain metallic implants, metallic foreign bodies or severe claustrophobia) 14. Contraindication to TMS 1. Implanted electronic cardiac devices (e.g., Automatic Implantable Cardioverter-Defibrillator \[AICD\] or pacemaker) 2. Any electronic devices in the body at or above the level of the seventh cervical vertebra (such as cochlear implant, cortical stimulator, deep brain stimulator, vagus nerve stimulator, cervical spine epidural stimulator, or ventriculoperitoneal shunt) 3. Ferromagnetic intracranial metallic implant 4. Skull defect related to current stroke 5. Seizure after onset of current stroke 6. Seizure within the last 12 months while taking anti-epileptic medications 7. Previous serious adverse reaction to TMS 15. Anticipated inability to perform study procedures within 168 hours of symptom onset 1. Unable to perform behavioral assessments within 48-120 hours of symptom onset (or time last known well). 2. Unable to receive TMS within 72-168 hours or get MRI within 48-168 hours of symptom onset (or time last known well).

Interventions

DIAGNOSTIC_TEST

Transcranial Magnetic Stimulation (TMS)

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Conditions

StrokeStroke, AcuteStroke, Ischemic

Locations

Birmingham VA Medical Center

Birmingham, Alabama 35233

United States

University of Alabama

Birmingham, Alabama 35233

United States

Banner University Medical Center

Tucson, Arizona 85719

United States

Keck Medical Center of USC

Los Angeles, California 90033

United States

Ronald Reagan UCLA Medical Center

Los Angeles, California 90095

United States

Kaiser Permanente Redwood City Medical Center

Redwood City, California 94063

United States

San Francisco General Hospital

San Francisco, California 94110

United States

UCSF Medical Center

San Francisco, California 94143

United States

Yale New Haven Hospital

New Haven, Connecticut 06511

United States

MedStar Washington Hospital Center

Washington D.C., District of Columbia 20010

United States

Emory University Hospital

Atlanta, Georgia 30322

United States

Memorial Hospital of Carbondale

Carbondale, Illinois 62901

United States

Advocate Lutheran General Hospital

Park Ridge, Illinois 60068

United States

IU Health Methodist Hospital

Indianapolis, Indiana 46202

United States

University of Iowa Hospitals & Clinics

Iowa City, Iowa 52242

United States

University of Maryland Medical Center

Baltimore, Maryland 21201

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Lahey Hospital & Medical Center

Burlington, Massachusetts 01805

United States

Baystate Medical Center

Springfield, Massachusetts 01199

United States

University of Michigan

Ann Arbor, Michigan 48108

United States

Corewell Heath Butterworth Hospital

Grand Rapids, Michigan 49503

United States

Mayo Clinic Saint Marys Campus

Rochester, Minnesota 55902

United States

NYU Langone Hospital - Brooklyn

Brooklyn, New York 11220

United States

The Mount Sinai Hospital

New York, New York 10029

United States

Strong Memorial Hospital

Rochester, New York 14642

United States

Montefiore Medical Center

The Bronx, New York 10467-0121

United States

Westchester Medical Center

Valhalla, New York 10595

United States

Duke University Hospital

Durham, North Carolina 27710

United States

University of Cincinnati Medical Center

Cincinnati, Ohio 45219

United States

OSU Wexner Medical Center

Columbus, Ohio 43210

United States

Penn State Hershey Medical Center

Hershey, Pennsylvania 17033

United States

Pennsylvania Hospital

Philadelphia, Pennsylvania 19107

United States

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania 15213

United States

Medical University of South Carolina (MUSC)

Charleston, South Carolina 29425

United States

Prisma Health Richland Hospital

Columbia, South Carolina 29203

United States

UT Southwestern Medical Center

Dallas, Texas 75390

United States

Houston Methodist Hospital

Houston, Texas 77030

United States

Memorial Hermann Texas Medical Center

Houston, Texas 77030

United States

University of Utah Healthcare

Salt Lake City, Utah 84132

United States

UVA Medical Center

Charlottesville, Virginia 22903

United States

Richmond VA Medical Center

Richmond, Virginia 23249

United States

Harborview Medical Center

Seattle, Washington 98104

United States

University of Wisconsin University Hospital

Madison, Wisconsin 53792

United States

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin 53215

United States

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States