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

Stroke Clinical Trial

— VERIFY  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05338697
• Other study ID #: G200291
• Status: Recruiting
• Start date: June 18, 2022
• Est. completion date: January 2027

Study information

• Verified date: January 2024
• Source: University of Cincinnati
• Contact: Pooja Khatri, MD
• Phone: 513-558-5478
• Email: pooja.khatri[@]uc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 poststroke.

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: 657 participants: 557 with ischemic stroke and 100 with intracerebral hemorrhage (exploratory cohort) enrolled at up to 35 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 657
• Est. completion date: January 2027
• Est. primary completion date: January 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 years or older

• Unilateral stroke due to ischemia or intracerebral hemorrhage

• Motor deficits in the acutely affected UE, defined as a Shoulder Abduction and Finger Extension (SAFE) score = 8 out of 10 points (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).

• Provision of signed and dated informed consent form within 48 to 96 hours of stroke onset (or time last known well).

• Stated willingness to comply with all study procedures and availability for the duration of the study

• Fluent in English or Spanish

Exclusion Criteria:

• UE injury or conditions on paretic side that limited use prior to the stroke.

• Legally blind.

• Dense sensory loss indicated by a score of 2 on NIHSS sensory item

• Unable to abduct the shoulder or extend the fingers of the non-paretic arm/hand/wrist on verbal command

• Isolated cerebellar stroke

• Bilateral hemisphere acute strokes

• 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

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

• Cognitive or communication impairment precluding informed consent by the participant.

• Major medical, neurological, or psychiatric condition that would substantially affect functional status

• Non-cerebrovascular diagnosis associated with unlikely survival at 90 days

• Pregnancy

• Contraindication to noncontrast MRI (i.e., certain metallic implants, metallic foreign bodies or severe claustrophobia)

• Contraindication to TMS (i.e., cardiac pacemaker or other 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; Skull defect related to current stroke; Seizure after onset of current stroke; Seizure within the last 12 months while taking anti-epileptic medications; Previous serious adverse reaction to TMS)

• Unable to perform behavioral assessments within 48-120 hours of symptom onset

• Unable to receive TMS or get MRI within 72-168 hours of symptom onset

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

Related Conditions & MeSH terms

• Hemorrhagic Stroke
• Ischemic Stroke
• Stroke
• Stroke Hemorrhagic
• Stroke, Acute
• Stroke, Ischemic

Intervention

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.

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Lahey Hospital & Medical Center	Burlington	Massachusetts
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	UVA Medical Center	Charlottesville	Virginia
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Prisma Health Richland Hospital	Columbia	South Carolina
United States	OSU Wexner Medical Center	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Duke University Hospital	Durham	North Carolina
United States	Corewell Heath Butterworth Hospital	Grand Rapids	Michigan
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Houston Methodist Hospital	Houston	Texas
United States	Memorial Hermann Texas Medical Center	Houston	Texas
United States	University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	University of Wisconsin University Hospital	Madison	Wisconsin
United States	Froedtert & Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Mount Sinai Hospital	New York	New York
United States	NYU Langone Medical Center - Tisch Hospital	New York	New York
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	UPMC Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	Strong Memorial Hospital	Rochester	New York
United States	University of Utah Healthcare	Salt Lake City	Utah
United States	San Francisco General Hospital	San Francisco	California
United States	UCSF Medical Center	San Francisco	California
United States	Harborview Medical Center	Seattle	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	MedStar Washington Hospital Center	Washington	District of Columbia

Sponsors (4)

Lead Sponsor	Collaborator
University of Cincinnati	Medical University of South Carolina, University of Auckland, New Zealand, University of California, Los Angeles

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Motor Activity Log (MAL)	MAL categorized as 0 to 3 versus >/=3 to 5.	90 days post-stroke
Other	modified Rankin Score (mRS)	mRS level (0-6)	90 days post-stroke
Primary	Upper Extremity-Fugl Meyer (UE-FM) for AIM 1	UE-FM score, as a continuous scale, adjusted for baseline score in analysis	90 days post-stroke
Primary	Action Research Arm Test (ARAT) for AIM 2	ARAT categorized as 'excellent', 'good', 'limited', or 'poor'	90 days post-stroke