URMC / Labs / Cerebrovascular and Neurocognitive Research Group (CNRG) / Stroke Trials

Stroke Trials

Acute Trials Sub-Acute Trials Out-Patient Trials Schifitto Lab

Acute Trials

Study	CHARM	MOST	The Role of Hyperoxia in Treatment of AIS	GIST
Site PI(s)	Benesch	Benesch	Dylla	Halterman/Schifitto
Coordinator	Prentiss	Prentiss	Dylla	Prifti
Sponsor	Biogen	StrokeNet/NINDS	TBD	UR
Description	IV Glyburide for the treatment of cerebral edema following large hemispheric infarction	Determine whether argatroban and/or eptifibatide + IV rt-PA is superior to placebo in improving outcomes in AIS patients treated with IV rt-PA	To evaluate the feasibility and gather preliminary data on safety/efficacy of brief, early hyperoxia (supplemental oxygen in normoxic patients) for acute ischemic stroke.	1) Assess markers of gut permeability and immune activation in AIS compared to AIS mimics, and, 2) Assess whether markers of gut dysfunction predict penumbra to core conversion
Enrollment Period	2 years	2 years	2.5 years	<1 year
Stroke Type	Ischemic, MCA territory (PCA/ ACA involvement is OK), Large Hemispheric Infarction	Acute Ischemic, treated with IV rt-PA	Acute ischemic stroke	Acute ischemic stroke

Inclusion Criteria	1) Patients 18-85 with AIS in MCA territory	1) Acute Ischemic Stroke	1. Capacity to consent (or LAR present) and be enrolled within 1 hour of ED arrival	1. Patient is 45-85 years old of any sex or race
	2) LHI defined by 80-300cm3 on CTP or MRI (DWI), or an ASPECTS score of 1-5 with involvement of at least 2 cortical areas	2) Treated with 0.9mg/kg IV rt-PA within 3 hours of LKW	2. Patient suspected to have AIS	2. Diagnosed acute ischemic stroke from presenting CT/CTA/CTP
	3) Screening NIHSS ≥ 10	3) Age ≥ 18	3. Patient ≥ 18 years old	3. RAPID perfusion scans for AIS patients will exhibit a CBF <30% of 0–150 mls, a Tmax>6 of 50–360 ml, a mismatch volume > 50 ml, and Tmax:CBV ratio of >2
	4) Able to receive study drug within 10 hours of LKW	4) NIHSS ≥ 6 prior to IV rt-PA	4. CTP shows perfusion:diffusion mismatch >1.8; CTP shows perfusion:diffusion mismatch volume >10ml	4. Controls (AIS mimics) will have Tmax and CBF scores of 0
	5) Eligibility must be confirmed after mechanical thrombectomy with a study MRI	5) Able to receive study drug within 60 minutes of initiation of IV rt-PA	5. Pulse oximetry 96% or greater on room air by triage vitals

Exclusion Criteria	1) Likely to have supportive care withdrawn in the 1st day	1) Previous stroke in the last 90 days	1. Patient requires supplemental oxygen	1. Isolated subcortical stroke
	2) commitment to decompressive craniectomy (crani-watch OK)	2) Previous ICH, neoplasm, SAH, or AVM	2. No respiratory comorbidities requiring pulmonary vasodilators or supplemental oxygen	2. Fever, cough, UTI, or diarrheal illness in the last 2 months
	3) Evidence of concurrent infarction in the contralateral hemisphere sufficiently serious as to affect functional outcome	3) Clinical presentation suggesting SAH, even if CT is clean	3. No history of disorders with systematic inflammation (e.g. SLE or IBD)	3. History of GI surgery (any) or inflammatory bowel disease
		4) Surgery or biopsy of parenchymal organ in past 30 days; Trauma with internal injuries or ulcerative wounds in the past 30 days; severe head trauma in the past 30 days; severe systematic hemorrhage in the past 30 days	4. Patient is a tPA or EVT candidate	4. Stroke of any type in the last year and/or any history of seizures or seizure at presentation

Sub-Acute Trials

STRONG Study	HEART	MC10	FLUORESCE
Busza	Busza	Busza	Sahin
Busza/Prentiss	Busza	Busza	Prentiss
UCI	TBD	TBD	UR
Determine how genetic polymorphisms interact with rehab therapy and stress to impact treatment-induced recovery after a stroke.	Create a focus group of patients with arm weakness to collect subjective responses to a prototype of a new system for monitoring motor rehabilitation.	Use new sensor technology to develop more effective neurorehabilitation methods by tracking patients' effort in therapeutic exercises and relative motor recovery.	Determine whether fluoxetine (Prozac) enhances post-stroke visual recovery in ischemic stroke survivors.
Up to 4 years ischemic or ICH	up to 3 60 minute sessions any stroke or neurological condition resulting in arm weakness	up to 2 days ischemic, hemorrhagic	6 months ischemic stroke resulting in homonymous hemianopia or quadrantanopia

1. Age ≥ 18	1. Age ≥ 18	1. 18 years of age or older	1. Age 18-85 admitted to SMH or HH with a neuro-imaging confirmed AIS
2. Stroke that is ischemic or intracerebral hemorrhage, onset 2-10 days prior, and radiologically confirmed (CT or MRI)	2. English speaking	2. English-speaking	2. Clinically verifiable right or left-sided homonymous hemianopia or quadrantanopia
3. Able to communicate in English	3. Able to understand and consent to the study	3. History of ischemic or hemorrhagic stroke, confirmed by imaging
4. Reasonable expectation patient can participate through month 12	4. Able to understand and consent to the study	4. Currently enrolled in rehabilitation therapy (either inpatient or outpatient) to treat upper limb weakness due to stroke
5. Reasonable likelihood that patient will receive standard of care rehabilitation therapy after discharge (acute rehab, SNF, or home therapies)	5. Some amount of weakness in one of their arms

1. Moderate-severe disability prior to stroke (pre-stroke modified Rankin scan >2).	1. Any medical condition that would make potentially unsafe for the patient to participate in physical therapy (as deemed by primary team or outpatient neurologist)	1. Aphasia or cognitive impairments that limit capacity for consent or following commands	1. NIHSS > 5
2. Had a major brain or nerve disease that was active immediately prior to the stroke	2. History of allergy or skin irritation to skin electrodes (such as EKG or telemetry electrodes)	2. Medical conditions that would make patient unfit/unsafe to participate in standard rehab therapy	2. Premorbid mRS >2
3. Was hospitalized for a mental health problem in the prior 24 months	3. Unable or unwilling to consent or to participate in the study.	3. History of medical conditions that may affect motor function (e.g. Parkinson's)	3. Premorbid visual field deficits, retinopathy, or optic neuropathy
4. History of a symptomatic stroke in the 90 days prior to the index stroke		4. Bilateral weakness, hemispatial neglect, visual field defects, history of injury or current pain in affected arm/shoulder	4. Premorbid depression (or depression identified on admission), or current use of antidepressant medication
5. History of moderate-severe traumatic brain injury, operationally defined as a traumatic even accompanied by LOC for >30 mins.		5. Allergy to sensor adhesive	5. Hemorrhagic transformation of index stroke, resulting in mass effect

Outpatient Trials

Study	CREST-2	ASPIRE	ARCADIA
Site PI(s)	Sahin	Benesch	Benesch
Coordinator	Prentiss	Prentiss	Prentiss
Sponsor	NINDS, Regeneron	NINDS	See previous - patients can also be recruited from clinic within 120 days of index stroke
Description	To determine if carotid endararectomy or stenting in conjunction with medical management is more effective than medical management alone in preventing strokes in patients with high-grade, asymptomatic carotid stenosis.	Test the efficacy and safety of apizaban compared with aspirin in patients with recent ICH and high-risk non-valvular AF
Enrollment Period	5 years
Stroke Type	n/a; prevention trial

Inclusion Criteria	1. ≥35 years old	TBD - protocol forthcoming	See previous
	2. ≥70% carotid stenosis (asymptomatic)
	3. No medical history of stroke or TIA ipsilateral to the stenosis within 180 days of randomization.
	4. mRS of 0 or 1 at time of consent
	5. Women must not be of child-bearing potential, or, have a negative pregnancy test prior to randomization

Exclusion Criteria	1. Intolerance or allergy to study medication	TBD - protocol forthcoming	See previous
	2. GI hemorrhage within 1 month prior to enrollment that would preclude antiplatelet therapy.
	3. Prior major ipsilateral stroke in the past with substantial residual disability (mRS≥2) that is likely to confound study outcomes
	4. Severe dementia
	5. History of major symptomatic intracranial hemorrhage within 12 months that was not related to anticoagulation

Schifitto Lab

Study	PrEP	cART	Vascular Aging	CSVD	CSVD MRE	AHA-Pulmonary Hypertension
Site PI(s)	Schifitto	Schifitto, Arduino	Schifitto, Maggirwar, Abe	Schifitto, Maggirwar	Schifitto	Schifitto
Coordinator	Crysler	Crysler	Crysler, Moscato	Crysler, Oh	Crysler, Oh	Crysler, Oh
Sponsor	Unfunded	NIH	National Heart, Lung, Blood Institute	NIH	NIH	AHA
Description	To determine whether chronic exposure to antiretroviral therapy alters brain structure and function.	To determine whether the cART-aging interaction is associated with CNS toxicity, to estimate the effect of residual HIV replication on brain function in the absence of cART and evaluate red blood cell fragility and its correlation to decreased cognitive abilities.	To determine whether chronic exposure to combination antiretroviral therapy (cART) and elevated plasma levels of sCD40L in older HIV infected individuals are associated with p90RSK activation leading to enhanced aging of monocytes (reduce telomere length, reduced efferocytosis) and whether these measures of monocyte aging are associated with markers of atherosclerosis [carotid intima-media thickness (CIMT) and carotid arterial stiffness (CAS)].	To determine whether in chronically infected and cART treated HIV infected individuals changes in vascular reactivity and white matter microstructural integrity are associated with levels of circulating PMCs	To assess whether HIV infection is associated with abnormalities in brain viscoelastic properties and whether these abnormalities are associated with systemic markers of immune activation (soluble CD14 and CD163, D-dimer, soluble tissue factor and TF+ monocytes).	To assess whether circulating LPS or exDll4 is associated with pulmonary artery pressure (PAP) in HIV infected individuals.
Enrollment Period		NA	NA	January 2018 - June 2019	August 2019-April 2020

Inclusion Criteria	HIV negative	Cohort dependent	On stable cART for at least 12 months	On stable cART for at least 3 months	Enrolled in CSVD and quotas unmet	HIV+
	On PrEP for at least 6 months	60-80 newly diagnosed HIV+, 80-100 HIV-, 15-30 Elite Controllers (LTNP)	Viral load < 200 copies	Viral load < 200 copies		> 18
	18 years+	> 18	> 45	70 HIV+ > 50, 40 HIV+ < 50, 110 HIV- matched

Exclusion Criteria	HIV positive	Severe psychiatric disorders, dementia	Symptomatic CVD, uncontrolled diabetes, uncontrolled hypertension, immunosupressant use, inflammatory conditions	Symptomatic CVD, uncontrolled diabetes, uncontrolled hypertension, immunosupressant use, inflammatory conditions	NA	Chemotherapy
	Severe psychiatric disorders, dementia	Seizures, head trauma, MS	Self reported drug/alcohol abuse	Severe psychiatric disorders, dementia		Inflammatory bowel disease
	Seizures, stroke, head trauma, MS	Self reported drug/alcohol abuse		Seizures, head trauma, MS
	Self reported drug/alcohol abuse	Metal implant, claustrophobia		Self reported drug/alcohol abuse
	Metal implant, claustrophobia			Metal implant, claustrophobia