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

NCT ID: NCT05338697

Last Updated: 2025-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

657 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-06-18

Study Completion Date

2027-10-31

Brief Summary

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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

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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.

Conditions

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Stroke Stroke, Acute Stroke, Ischemic

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Ischemic & Hemorrhagic stroke patients

up to 657 stroke patients

Transcranial Magnetic Stimulation (TMS)

Intervention Type DIAGNOSTIC_TEST

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.

Interventions

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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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of California, Los Angeles

OTHER

Sponsor Role collaborator

University of Auckland, New Zealand

OTHER

Sponsor Role collaborator

Medical University of South Carolina

OTHER

Sponsor Role collaborator

University of Cincinnati

OTHER

Sponsor Role lead

Responsible Party

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Pooja Khatri

Professor & Chair of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pooja Khatri, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Steve Cramer, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Cathy Stinear, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Auckland, New Zealand

Achala Vagal, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

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Birmingham VA Medical Center

Birmingham, Alabama, United States

Site Status RECRUITING

University of Alabama

Birmingham, Alabama, United States

Site Status RECRUITING

Banner University Medical Center

Tucson, Arizona, United States

Site Status NOT_YET_RECRUITING

Keck Medical Center of USC

Los Angeles, California, United States

Site Status RECRUITING

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Site Status WITHDRAWN

Kaiser Permanente Redwood City Medical Center

Redwood City, California, United States

Site Status NOT_YET_RECRUITING

San Francisco General Hospital

San Francisco, California, United States

Site Status RECRUITING

UCSF Medical Center

San Francisco, California, United States

Site Status RECRUITING

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status NOT_YET_RECRUITING

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Emory University Hospital

Atlanta, Georgia, United States

Site Status RECRUITING

Memorial Hospital of Carbondale

Carbondale, Illinois, United States

Site Status NOT_YET_RECRUITING

Advocate Lutheran General Hospital

Park Ridge, Illinois, United States

Site Status NOT_YET_RECRUITING

IU Health Methodist Hospital

Indianapolis, Indiana, United States

Site Status NOT_YET_RECRUITING

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status RECRUITING

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status ACTIVE_NOT_RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Lahey Hospital & Medical Center

Burlington, Massachusetts, United States

Site Status RECRUITING

Baystate Medical Center

Springfield, Massachusetts, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Corewell Heath Butterworth Hospital

Grand Rapids, Michigan, United States

Site Status RECRUITING

Mayo Clinic Saint Marys Campus

Rochester, Minnesota, United States

Site Status NOT_YET_RECRUITING

NYU Langone Hospital - Brooklyn

Brooklyn, New York, United States

Site Status SUSPENDED

The Mount Sinai Hospital

New York, New York, United States

Site Status RECRUITING

Strong Memorial Hospital

Rochester, New York, United States

Site Status RECRUITING

Montefiore Medical Center

The Bronx, New York, United States

Site Status RECRUITING

Westchester Medical Center

Valhalla, New York, United States

Site Status RECRUITING

Duke University Hospital

Durham, North Carolina, United States

Site Status RECRUITING

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

OSU Wexner Medical Center

Columbus, Ohio, United States

Site Status RECRUITING

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status RECRUITING

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Medical University of South Carolina (MUSC)

Charleston, South Carolina, United States

Site Status RECRUITING

Prisma Health Richland Hospital

Columbia, South Carolina, United States

Site Status RECRUITING

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

Houston Methodist Hospital

Houston, Texas, United States

Site Status WITHDRAWN

Memorial Hermann Texas Medical Center

Houston, Texas, United States

Site Status RECRUITING

University of Utah Healthcare

Salt Lake City, Utah, United States

Site Status RECRUITING

UVA Medical Center

Charlottesville, Virginia, United States

Site Status RECRUITING

Richmond VA Medical Center

Richmond, Virginia, United States

Site Status NOT_YET_RECRUITING

Harborview Medical Center

Seattle, Washington, United States

Site Status RECRUITING

University of Wisconsin University Hospital

Madison, Wisconsin, United States

Site Status RECRUITING

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status NOT_YET_RECRUITING

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Pooja Khatri, MD

Role: CONTACT

203-747-4730

Kalli Beasley, MPH

Role: CONTACT

707-372-6241

Facility Contacts

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Michael Lyerly, MD

Role: primary

Toby Gropen, MD

Role: primary

Firas Kaddouh, MD, MHS

Role: primary

Sook-Lei Liew, PhD, OTR/L

Role: primary

Sheila Chan, MD

Role: primary

Cathra Halabi, MD

Role: primary

Cathra Halabi, MD

Role: primary

Rebecca DiBiase, MD

Role: primary

Matt Edwardson, MD

Role: primary

202-687-2184

Michael Borich, PT, PhD

Role: primary

404-640-3150

Andrea Loggini, MD

Role: primary

Anit Behera, MD

Role: primary

Ann Jones, MD

Role: primary

Hannah Roeder, MD, MPH

Role: primary

319-356-8755

David J Lin, MD

Role: primary

Siddharth Sehgal, MD

Role: primary

Gottfried Schlaug, MD, PhD

Role: primary

617-319-5953

Chandramouli Krishnan, PT, PhD

Role: primary

Malgorzata M Miller, MD

Role: primary

M

Role: backup

Muhib Khan, MBBS, MD, RPNI

Role: primary

Neha Dangayach, MD

Role: primary

Ania Busza, MD, PhD

Role: primary

Cynthia Hung, MD

Role: primary

Tomoko Kitago, MD

Role: primary

Wayne Feng, MD

Role: primary

919-684-3801

Oluwole Awosika, MD

Role: primary

513-558-5328

Yousef Hannawi, MD

Role: primary

614-685-7234

Raymond Reichwein, MD

Role: primary

717-461-1220

Kelly Sloan, MD

Role: primary

George Wittenberg, MD, PhD

Role: primary

412- 648-4178

Kirstin Heise, PhD

Role: primary

843-792-3435

Forrest Lowe, MD

Role: primary

Benjamin Nguyen, MD

Role: primary

214-633-4794

Sean Savitz, MD

Role: primary

617-233-1988

Lorie Richards, PhD

Role: primary

352-317-1023

Chad Aldridge, PT, PhD

Role: primary

Sherita Chapman, MD

Role: primary

Nicole Mazwi, MD

Role: primary

Azam S. Ahmed, MD

Role: primary

608-201-0957

Thomas Wolfe, MD

Role: primary

Caitlin Moore, MD

Role: primary

Related Links

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https://theverifystudy.com/

Information about the study.

Other Identifiers

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G200291

Identifier Type: -

Identifier Source: org_study_id

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