Clinical trial NCT02121028: Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease
Official title: Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Intracranial Vascular Disorders
Keywords: Intracranial Atherosclerotic Disease
Stroke
Transient Ischemic Attack
Imaging
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
name: Northwestern University
name: Emory University
name: Baystate Medical Center
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2014-04-23
Enrollment: 105
Sex: ALL
Minimum age (years): 30
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Eligible patients will have a recent stroke or TIA due to intracranial Atherosclerotic Disease (IAD) of 50-99% .

Brief summary: The objective of this study is to determine the mechanisms of stroke in patients with Intracranial Atherosclerotic Disease (IAD) by specifically evaluating limitations of antegrade flow through the stenotic artery, distal tissue perfusion to the affected territory, and artery-to-artery embolism. The hypothesis is that non-invasive imaging biomarkers that stratify stroke risk and distinguish mechanisms of IAD. This prospective multicenter study will enroll 175 patients with recently symptomatic high-grade IAD. Patients will be studied within 21 days of the index event (allowing appropriate time to arrange for diverse imaging modalities), with the following advanced neuroimaging techniques to elucidate mechanisms of recurrent ischemia:

* Quantitative magnetic resonance imaging (QMRA) to assess volumetric flow rate through the stenotic artery.
* Magnetic resonance perfusion weighted imaging (PWI-MRI) to determine distal tissue perfusion.
* Vasomotor reactivity by Transcranial Doppler using the breath-holding technique (BHI-TCD) to assess compensatory flow characteristics to the territory distal to the affected artery;
* Transcranial Doppler with embolic signal monitoring to evaluate artery-to-artery embolism that reflects plaque instability.

Patients will receive standardized medical management and its effectiveness on blood pressure, lipid, and glycemic control will be monitored.

The primary outcome is recurrent stroke in the territory of the stenotic artery during a 1-year follow-up period; secondary outcomes are: a) new asymptomatic ischemic lesions on MRI in the distribution of the stenotic artery at 6-8 weeks, and b) transient ischemic attack (TIA) in the distribution of the stenotic artery during a 1-year follow-up period.

Patients will be recruited at various sites that will be trained and certified on the imaging techniques employed. Raw imaging data will be interpreted centrally.


Eligibility criteria: Inclusion Criteria:

1. Stroke defined as symptoms lasting \>24 hours and associated with imaging evidence of acute ischemia in the distribution of the stenotic vessel on CT or MRI.
2. Eligible TIA defined as transient neurological symptoms lasting \<24 hours, need to be:

   1. accompanied by DWI abnormalities in the distribution of the stenotic artery; or
   2. multiple (≥2), stereotyped events associated with unequivocal ischemic symptoms (weakness, aphasia), and attributed to the symptomatic artery.
3. IAD should involve the intracranial carotid, middle cerebral, intracranial vertebral or basilar arteries.
4. Stenosis 50-99% quantified by digital subtraction angiography (DSA), CT angiography-CTA or MR angiography-MRA tests. DSA is not required but will be used if obtained as part of clinical care.

   The criteria for 50-99% are:
   1. CTA or DSA: measured 50-99% stenosis by WASID criteria (percent stenosis = (1-\[diameter stenosis/diameter normal\]) x 100%.
   2. MRA: measured 50-99% stenosis or presence of a flow gap.
5. Age \>30; those 30-49 years of age must also have the presence of established atherosclerotic disease in another vascular bed (coronary, extracranial carotid, peripheral) or the presence of 2 or more risk factors (hypertension, diabetes mellitus, hyperlipidemia, tobacco abuse within the last 2 years).
6. Enrollment within 21 days of symptom onset and completion of study imaging tests within 21 days of index event (stroke or TIA).
7. Provide informed consent for participation in the study.

Exclusion Criteria:

1. Other cause for stroke: atrial fibrillation, acute anterior wall ST-elevation myocardial infarction \<30days, mitral stenosis, mechanical valve, intracardiac thrombus or vegetation, dilated cardiomyopathy or ejection fraction \<30%, proximal extracranial carotid or vertebral stenosis \>50%.
2. Contraindications to MRI, including MR-incompatible metallic implants, implanted electronic devices, other potentially mobile ferromagnetic material, pregnancy (women in fertile age should have a negative pregnancy test), lactation, morbid obesity, and severe claustrophobia.
3. Renal impairment defined as either a creatinine level \>1.5 mg/dL or a glomerular filtration rate (GFR) \<30 mL/min/1.73 m2.
4. Known allergy to gadolinium.
5. Unable to obtain informed consent by patient or legally authorized representative.
6. Severe behavioral or social problems that may interfere with the conduct of the study.
7. In the investigator's opinion, patient unlikely return for follow up visit and to complete the study.
8. Participation in a drug or device clinical trial within the last 30 days.

Primary outcomes:
measure: Recurrent stroke in the territory of the symptomatic artery
timeFrame: 1 year
Secondary outcomes:
measure: TIA in the territory of the stenotic artery
timeFrame: 1 year
measure: Silent infarcts in the distribution of the stenotic artery
timeFrame: 6-8 weeks
Other outcomes:
measure: Risk of combined microembolic signals and impaired vasomotor reactivity.
timeFrame: 1 year
measure: Risk of combined poor ante grade flow and poor distal tissue perfusion.
timeFrame: 1 year
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Northwestern University Department of Radiology
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Miami
name: Jose G Romano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Chicago
name: Shyam Prabhakaran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: David S Liebeskind, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Prabhakaran S, Liebeskind DS, Cotsonis G, Nizam A, Feldmann E, Sangha RS, Campo-Bustillo I, Romano JG; MYRIAD Investigators. Predictors of Early Infarct Recurrence in Patients With Symptomatic Intracranial Atherosclerotic Disease. Stroke. 2021 Jun;52(6):1961-1966. doi: 10.1161/STROKEAHA.120.032676. Epub 2021 Apr 19.
citation: Romano JG, Prabhakaran S, Nizam A, Feldmann E, Sangha R, Cotsonis G, Campo-Bustillo I, Koch S, Rundek T, Chimowitz MI, Liebeskind DS; MyRIAD Investigators. Infarct Recurrence in Intracranial Atherosclerosis: Results from the MyRIAD Study. J Stroke Cerebrovasc Dis. 2021 Feb;30(2):105504. doi: 10.1016/j.jstrokecerebrovasdis.2020.105504. Epub 2020 Dec 1.