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

Last updated: October 12, 2025
Sponsor: University of Cincinnati
Overall Status: Active - Recruiting

Phase

N/A

Condition

Thrombosis

Cerebral Ischemia

Stroke

Treatment

Transcranial Magnetic Stimulation (TMS)

Clinical Study ID

NCT05338697
G200291
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Age 18 years or older

  2. Unilateral symptomatic stroke due to ischemia. (Note: Bilateral acute stroke ispermitted 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 andFinger Extension (SAFE) score ≤ 8 out of 10 points20,61 (i.e., excluding full ornearly 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 studymemo.

  4. Provision of signed and dated informed consent form within 24 to 96 hours of strokeonset, (or time last known well). Note: Participant is considered "enrolled" uponstarting TMS (at least one stimulation is delivered) or starting study-specific MRIpulse sequence (at least one MRI beep occurs)

  5. Stated willingness to comply with all study procedures and availability for theduration of the study, including Day 90 visit which must occur in-person.

  6. Fluent in study approved languages (i.e., English or Spanish)

Exclusion

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 verbalcommand

  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 (acutetreatment or rehabilitation/recovery intervention) after baseline assessments forVERIFY are initiated

  8. Known or expected inability to maintain follow-up with study procedures through 90days

  9. Cognitive or communication impairment precluding informed consent by theparticipant.

  10. Major medical, neurological, or psychiatric condition that would substantiallyaffect functional status

  11. Non-cerebrovascular diagnosis associated with unlikely survival at 90 days

  12. Pregnancy

  13. Contraindication to noncontrast MRI (certain metallic implants, metallic foreignbodies or severe claustrophobia)

  14. Contraindication to TMS

  15. Implanted electronic cardiac devices (e.g., Automatic ImplantableCardioverter-Defibrillator [AICD] or pacemaker)

  16. Any electronic devices in the body at or above the level of the seventhcervical vertebra (such as cochlear implant, cortical stimulator, deep brainstimulator, vagus nerve stimulator, cervical spine epidural stimulator, orventriculoperitoneal shunt)

  17. Ferromagnetic intracranial metallic implant

  18. Skull defect related to current stroke

  19. Seizure after onset of current stroke

  20. Seizure within the last 12 months while taking anti-epileptic medications

  21. Previous serious adverse reaction to TMS

  22. Anticipated inability to perform study procedures within 168 hours of symptom onset

  23. Unable to perform behavioral assessments within 48-120 hours of symptom onset (or time last known well).

  24. Unable to receive TMS within 72-168 hours or get MRI within 48-168 hours ofsymptom onset (or time last known well).

Study Design

Total Participants: 657
Treatment Group(s): 1
Primary Treatment: Transcranial Magnetic Stimulation (TMS)
Phase:
Study Start date:
June 18, 2022
Estimated Completion Date:
October 31, 2027

Study 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.

Connect with a study center

  • University of Alabama

    Birmingham, Alabama 35233
    United States

    Site Not Available

  • Birmingham VA Medical Center

    Birmingham 4049979, Alabama 4829764 35233
    United States

    Active - Recruiting

  • University of Alabama

    Birmingham 4049979, Alabama 4829764 35233
    United States

    Active - Recruiting

  • Banner University Medical Center

    Tucson 5318313, Arizona 5551752 85719
    United States

    Site Not Available

  • Ronald Reagan UCLA Medical Center

    Los Angeles, California 90095
    United States

    Site Not Available

  • San Francisco General Hospital

    San Francisco, California 94110
    United States

    Site Not Available

  • UCSF Medical Center

    San Francisco, California 94143
    United States

    Active - Recruiting

  • Keck Medical Center of USC

    Los Angeles 5368361, California 5332921 90033
    United States

    Active - Recruiting

  • Ronald Reagan UCLA Medical Center

    Los Angeles 5368361, California 5332921 90095
    United States

    Site Not Available

  • Kaiser Permanente Redwood City Medical Center

    Redwood City 5386834, California 5332921 94063
    United States

    Site Not Available

  • San Francisco General Hospital

    San Francisco 5391959, California 5332921 94110
    United States

    Active - Recruiting

  • UCSF Medical Center

    San Francisco 5391959, California 5332921 94143
    United States

    Active - Recruiting

  • Yale New Haven Hospital

    New Haven 4839366, Connecticut 4831725 06511
    United States

    Site Not Available

  • MedStar Washington Hospital Center

    Washington, District of Columbia 20010
    United States

    Site Not Available

  • MedStar Washington Hospital Center

    Washington D.C. 4140963, District of Columbia 4138106 20010
    United States

    Active - Recruiting

  • Emory University Hospital

    Atlanta, Georgia 30322
    United States

    Site Not Available

  • Emory University Hospital

    Atlanta 4180439, Georgia 4197000 30322
    United States

    Active - Recruiting

  • Memorial Hospital of Carbondale

    Carbondale 4235193, Illinois 4896861 62901
    United States

    Site Not Available

  • Advocate Lutheran General Hospital

    Park Ridge 4905367, Illinois 4896861 60068
    United States

    Site Not Available

  • IU Health Methodist Hospital

    Indianapolis 4259418, Indiana 4921868 46202
    United States

    Site Not Available

  • University of Iowa Hospitals & Clinics

    Iowa City, Iowa 52242
    United States

    Site Not Available

  • University of Iowa Hospitals & Clinics

    Iowa City 4862034, Iowa 4862182 52242
    United States

    Active - Recruiting

  • University of Maryland Medical Center

    Baltimore, Maryland 21201
    United States

    Site Not Available

  • University of Maryland Medical Center

    Baltimore 4347778, Maryland 4361885 21201
    United States

    Site Not Available

  • Massachusetts General Hospital

    Boston, Massachusetts 02114
    United States

    Site Not Available

  • Lahey Hospital & Medical Center

    Burlington, Massachusetts 01805
    United States

    Site Not Available

  • Baystate Medical Center

    Springfield, Massachusetts 01199
    United States

    Site Not Available

  • Massachusetts General Hospital

    Boston 4930956, Massachusetts 6254926 02114
    United States

    Active - Recruiting

  • Lahey Hospital & Medical Center

    Burlington 4931737, Massachusetts 6254926 01805
    United States

    Active - Recruiting

  • Baystate Medical Center

    Springfield 4951788, Massachusetts 6254926 01199
    United States

    Active - Recruiting

  • University of Michigan

    Ann Arbor, Michigan 48108
    United States

    Site Not Available

  • Corewell Heath Butterworth Hospital

    Grand Rapids, Michigan 49503
    United States

    Site Not Available

  • University of Michigan

    Ann Arbor 4984247, Michigan 5001836 48108
    United States

    Active - Recruiting

  • Corewell Heath Butterworth Hospital

    Grand Rapids 4994358, Michigan 5001836 49503
    United States

    Active - Recruiting

  • Mayo Clinic Saint Marys Campus

    Rochester 5043473, Minnesota 5037779 55902
    United States

    Site Not Available

  • Montefiore Medical Center

    Bronx, New York 10467-0121
    United States

    Site Not Available

  • Mount Sinai Hospital

    New York, New York 10029
    United States

    Site Not Available

  • NYU Langone Medical Center - Tisch Hospital

    New York, New York 10016
    United States

    Active - Recruiting

  • Strong Memorial Hospital

    Rochester, New York 14642
    United States

    Site Not Available

  • NYU Langone Hospital - Brooklyn

    Brooklyn 5110302, New York 5128638 11220
    United States

    Suspended

  • The Mount Sinai Hospital

    New York 5128581, New York 5128638 10029
    United States

    Active - Recruiting

  • Strong Memorial Hospital

    Rochester 5134086, New York 5128638 14642
    United States

    Active - Recruiting

  • Montefiore Medical Center

    The Bronx 5110266, New York 5128638 10467-0121
    United States

    Active - Recruiting

  • Westchester Medical Center

    Valhalla 5142090, New York 5128638 10595
    United States

    Active - Recruiting

  • Duke University Hospital

    Durham, North Carolina 27710
    United States

    Site Not Available

  • Duke University Hospital

    Durham 4464368, North Carolina 4482348 27710
    United States

    Active - Recruiting

  • University of Cincinnati Medical Center

    Cincinnati, Ohio 45219
    United States

    Site Not Available

  • OSU Wexner Medical Center

    Columbus, Ohio 43210
    United States

    Site Not Available

  • University of Cincinnati Medical Center

    Cincinnati 4508722, Ohio 5165418 45219
    United States

    Active - Recruiting

  • OSU Wexner Medical Center

    Columbus 4509177, Ohio 5165418 43210
    United States

    Active - Recruiting

  • Penn State Hershey Medical Center

    Hershey, Pennsylvania 17033
    United States

    Site Not Available

  • Pennsylvania Hospital

    Philadelphia, Pennsylvania 19107
    United States

    Site Not Available

  • UPMC Presbyterian Hospital

    Pittsburgh, Pennsylvania 15213
    United States

    Site Not Available

  • Penn State Hershey Medical Center

    Hershey 5193342, Pennsylvania 6254927 17033
    United States

    Active - Recruiting

  • Pennsylvania Hospital

    Philadelphia 4560349, Pennsylvania 6254927 19107
    United States

    Active - Recruiting

  • UPMC Presbyterian Hospital

    Pittsburgh 5206379, Pennsylvania 6254927 15213
    United States

    Active - Recruiting

  • Medical University of South Carolina (MUSC)

    Charleston, South Carolina 29425
    United States

    Site Not Available

  • Prisma Health Richland Hospital

    Columbia, South Carolina 29203
    United States

    Site Not Available

  • Medical University of South Carolina (MUSC)

    Charleston 4574324, South Carolina 4597040 29425
    United States

    Active - Recruiting

  • Prisma Health Richland Hospital

    Columbia 4575352, South Carolina 4597040 29203
    United States

    Active - Recruiting

  • UT Southwestern Medical Center

    Dallas, Texas 75390
    United States

    Site Not Available

  • Houston Methodist Hospital

    Houston, Texas 77030
    United States

    Site Not Available

  • Memorial Hermann Texas Medical Center

    Houston, Texas 77030
    United States

    Active - Recruiting

  • UT Southwestern Medical Center

    Dallas 4684888, Texas 4736286 75390
    United States

    Active - Recruiting

  • Houston Methodist Hospital

    Houston 4699066, Texas 4736286 77030
    United States

    Site Not Available

  • Memorial Hermann Texas Medical Center

    Houston 4699066, Texas 4736286 77030
    United States

    Active - Recruiting

  • University of Utah Healthcare

    Salt Lake City, Utah 84132
    United States

    Site Not Available

  • University of Utah Healthcare

    Salt Lake City 5780993, Utah 5549030 84132
    United States

    Active - Recruiting

  • UVA Medical Center

    Charlottesville, Virginia 22903
    United States

    Site Not Available

  • UVA Medical Center

    Charlottesville 4752031, Virginia 6254928 22903
    United States

    Active - Recruiting

  • Richmond VA Medical Center

    Richmond 4781708, Virginia 6254928 23249
    United States

    Site Not Available

  • Harborview Medical Center

    Seattle, Washington 98104
    United States

    Site Not Available

  • Harborview Medical Center

    Seattle 5809844, Washington 5815135 98104
    United States

    Active - Recruiting

  • University of Wisconsin University Hospital

    Madison, Wisconsin 53792
    United States

    Site Not Available

  • Froedtert & Medical College of Wisconsin

    Milwaukee, Wisconsin 53226
    United States

    Site Not Available

  • University of Wisconsin University Hospital

    Madison 5261457, Wisconsin 5279468 53792
    United States

    Active - Recruiting

  • Aurora St. Luke's Medical Center

    Milwaukee 5263045, Wisconsin 5279468 53215
    United States

    Site Not Available

  • Froedtert & Medical College of Wisconsin

    Milwaukee 5263045, Wisconsin 5279468 53226
    United States

    Active - Recruiting

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