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

October 12, 2025 updated by: Pooja Khatri, University of Cincinnati
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

657

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama
        • Contact:
        • Principal Investigator:
          • Toby Gropen, MD
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • Birmingham VA Medical Center
        • Contact:
        • Principal Investigator:
          • Michael Lyerly, MD
    • Arizona
      • Tucson, Arizona, United States, 85719
    • California
      • Los Angeles, California, United States, 90033
        • Recruiting
        • Keck Medical Center of USC
        • Contact:
        • Principal Investigator:
          • Sook-Lei Liew, PhD, OTR/L
      • Los Angeles, California, United States, 90095
        • Withdrawn
        • Ronald Reagan UCLA Medical Center
      • Redwood City, California, United States, 94063
        • Not yet recruiting
        • Kaiser Permanente Redwood City Medical Center
        • Principal Investigator:
          • Sheila Chan, MD
        • Contact:
      • San Francisco, California, United States, 94110
        • Recruiting
        • San Francisco General Hospital
        • Contact:
        • Principal Investigator:
          • Cathra Halabi, MD
      • San Francisco, California, United States, 94143
        • Recruiting
        • UCSF Medical Center
        • Contact:
        • Principal Investigator:
          • Cathra Halabi, MD
    • Connecticut
      • New Haven, Connecticut, United States, 06511
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Recruiting
        • MedStar Washington Hospital Center
        • Contact:
        • Principal Investigator:
          • Matt Edwardson, MD
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University Hospital
        • Contact:
        • Principal Investigator:
          • Michael Borich, PT, PhD
    • Illinois
      • Carbondale, Illinois, United States, 62901
        • Not yet recruiting
        • Memorial Hospital of Carbondale
        • Contact:
        • Principal Investigator:
          • Andrea Loggini, MD
      • Park Ridge, Illinois, United States, 60068
        • Not yet recruiting
        • Advocate Lutheran General Hospital
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Not yet recruiting
        • IU Health Methodist Hospital
        • Contact:
        • Principal Investigator:
          • Ann Jones, MD
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa Hospitals & Clinics
        • Principal Investigator:
          • Hannah Roeder, MD
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Active, not recruiting
        • University of Maryland Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
          • David J Lin, MD
        • Principal Investigator:
          • David J Lin, MD
      • Burlington, Massachusetts, United States, 01805
        • Recruiting
        • Lahey Hospital & Medical Center
        • Contact:
        • Principal Investigator:
          • Siddharth Sehgal
      • Springfield, Massachusetts, United States, 01199
        • Recruiting
        • Baystate Medical Center
        • Contact:
        • Principal Investigator:
          • Gottfried Schlaug, MD, PhD
    • Michigan
      • Ann Arbor, Michigan, United States, 48108
        • Recruiting
        • University of Michigan
        • Contact:
        • Principal Investigator:
          • Chandramouli Krishnan, PT, PhD
      • Grand Rapids, Michigan, United States, 49503
    • Minnesota
      • Rochester, Minnesota, United States, 55902
        • Not yet recruiting
        • Mayo Clinic Saint Marys Campus
        • Contact:
        • Principal Investigator:
          • Muhib Khan, MBBS, MD, RPNI
    • New York
      • Brooklyn, New York, United States, 11220
        • Suspended
        • NYU Langone Hospital - Brooklyn
      • New York, New York, United States, 10029
        • Recruiting
        • The Mount Sinai Hospital
        • Contact:
        • Principal Investigator:
          • Neha Dangayach, MD
      • Rochester, New York, United States, 14642
        • Recruiting
        • Strong Memorial Hospital
        • Contact:
        • Principal Investigator:
          • Ania Busza, MD, PhD
      • The Bronx, New York, United States, 10467-0121
        • Recruiting
        • Montefiore Medical Center
        • Contact:
        • Principal Investigator:
          • Cynthia Hung, MD
      • Valhalla, New York, United States, 10595
        • Recruiting
        • Westchester Medical Center
        • Principal Investigator:
          • Tomoko Kitago, MD
        • Contact:
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Hospital
        • Contact:
        • Principal Investigator:
          • Wayne Feng, MD
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Medical Center
        • Principal Investigator:
          • Oluwole Awosika, MD
        • Contact:
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • OSU Wexner Medical Center
        • Contact:
        • Principal Investigator:
          • Yousef Hannawi, MD
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Recruiting
        • Penn State Hershey Medical Center
        • Principal Investigator:
          • Raymond Reichwein, MD
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19107
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • UPMC Presbyterian Hospital
        • Principal Investigator:
          • George Wittenberg, MD, PhD
        • Contact:
          • George Wittenberg, MD, PhD
          • Phone Number: 412- 648-4178
          • Email: geowitt@pitt.edu
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina (MUSC)
        • Contact:
        • Principal Investigator:
          • Kirstin Heise, PhD
      • Columbia, South Carolina, United States, 29203
        • Recruiting
        • Prisma Health Richland Hospital
        • Contact:
        • Principal Investigator:
          • Forrest Lowe, MD
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern Medical Center
        • Contact:
        • Principal Investigator:
          • Benjamin Nguyen, MD
      • Houston, Texas, United States, 77030
        • Recruiting
        • Memorial Hermann Texas Medical Center
        • Principal Investigator:
          • Sean Savitz, MD
        • Contact:
      • Houston, Texas, United States, 77030
        • Withdrawn
        • Houston Methodist Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Recruiting
        • University of Utah Healthcare
        • Contact:
        • Principal Investigator:
          • Lorie Richards, PhD
        • Sub-Investigator:
          • Jennifer Majersik
    • Virginia
      • Charlottesville, Virginia, United States, 22903
      • Richmond, Virginia, United States, 23249
    • Washington
      • Seattle, Washington, United States, 98104
        • Recruiting
        • Harborview Medical Center
        • Contact:
        • Principal Investigator:
          • David Tirschwell, MD, MSc
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin University Hospital
        • Contact:
        • Principal Investigator:
          • Azam S. Ahmed, MD
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Froedtert & Medical College of Wisconsin
        • Contact:
        • Principal Investigator:
          • Caitlin Moore, MD
      • Milwaukee, Wisconsin, United States, 53215
        • Not yet recruiting
        • Aurora St. Luke's Medical Center
        • Contact:
        • Principal Investigator:
          • Thomas Wolfe, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with ischemic stroke consented within 24-96 hours of stroke onset in the acute hospitalization setting

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Ischemic & Hemorrhagic stroke patients
up to 657 stroke patients
Diagnostic test: Transcranial Magnetic Stimulation (TMS)
No intervention used. This study is using TMS to obtain motor evoked potential (MEP), a prognostic biomarker. The TMS procedure is being conducted during the first week of hospitalization, which required registration under an IDE. Only TMS devices that have received 510(k) clearance from the FDA are used in this study, consisting of MEGA-TMS and MagStim 200-2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Upper Extremity-Fugl Meyer (UE-FM) for AIM 1
Time Frame: 90 days post-stroke
UE-FM score, as a continuous scale, adjusted for baseline score in analysis
90 days post-stroke
Action Research Arm Test (ARAT) for AIM 2
Time Frame: 90 days post-stroke
ARAT categorized as 'excellent', 'good', 'limited', or 'poor'
90 days post-stroke

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Motor Activity Log (MAL)
Time Frame: 90 days post-stroke
MAL categorized as 0 to 3 versus >/=3 to 5.
90 days post-stroke
modified Rankin Score (mRS)
Time Frame: 90 days post-stroke
mRS level (0-6)
90 days post-stroke

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Cincinnati

Collaborators

Medical University of South Carolina
University of California, Los Angeles
University of Auckland, New Zealand

Investigators

  • Principal Investigator: Steve Cramer, MD, University of California, Los Angeles
  • Principal Investigator: Cathy Stinear, PhD, University of Auckland, New Zealand
  • Principal Investigator: Achala Vagal, MD, University of Cincinnati
  • Principal Investigator: Pooja Khatri, MD, Yale University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 18, 2022

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

October 1, 2027

Study Registration Dates

First Submitted

April 13, 2022

First Submitted That Met QC Criteria

April 13, 2022

First Posted (Actual)

April 21, 2022

Study Record Updates

Last Update Posted (Estimated)

October 15, 2025

Last Update Submitted That Met QC Criteria

October 12, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • G200291

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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