Clinical trial NCT05338697: Validation of Early Prognostic Data for Recovery Outcome After Stroke for Future, Higher Yield Trials
Official title: Validation of Early Prognostic Data for Recovery Outcome After Stroke for Future, Higher Yield Trials
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Stroke
Stroke, Acute
Stroke, Ischemic
Stroke Hemorrhagic
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
name: University of Auckland, New Zealand
name: Medical University of South Carolina
First posted: 2022-04-21
Enrollment: 657
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with ischemic or intracerebral hemorrhage consented within 48-96 hours of stroke onset in the acute hospitalization setting

Brief 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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Upper Extremity-Fugl Meyer (UE-FM) for AIM 1
timeFrame: 90 days post-stroke
measure: Action Research Arm Test (ARAT) for AIM 2
timeFrame: 90 days post-stroke
Secondary outcomes:
Other outcomes:
measure: Motor Activity Log (MAL)
timeFrame: 90 days post-stroke
measure: modified Rankin Score (mRS)
timeFrame: 90 days post-stroke
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: San Francisco General Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Heath Butterworth Hospital
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center - Tisch Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Rochester
country: United States
facility: Strong Memorial Hospital
state: New York
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Columbus
country: United States
facility: OSU Wexner Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Columbia
country: United States
facility: Prisma Health Richland Hospital
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Texas Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Healthcare
state: Utah
city: Charlottesville
country: United States
facility: UVA Medical Center
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin University Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert & Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Cincinnati
name: Pooja Khatri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Steve Cramer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Auckland, New Zealand
name: Cathy Stinear, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cincinnati
name: Achala Vagal, MD
role: PRINCIPAL_INVESTIGATOR
References: