Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease

NCT ID: NCT02121028

Last Updated: 2021-05-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 105 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-05-01
• Study Completion Date: 2020-12-31

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.

Conditions

Intracranial Vascular Disorders

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Intracranial Atherosclerotic Disease, Stroke/TIA

Stroke/TIA due to high grade IAD ≤21 days from symptom onset.

No interventions assigned to this group

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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: collaborator

Baystate Medical Center

OTHER

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Jose Romano, MD

Professor of Clinical Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jose G Romano, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Shyam Prabhakaran, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

David S Liebeskind, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

UCLA

Los Angeles, California, United States

University of Florida

Gainesville, Florida, United States

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

University of Miami

Miami, Florida, United States

Northwestern University Department of Radiology

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

Columbia University Medical Center

New York, New York, United States

Medical University of South Carolina

Charleston, South Carolina, United States

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33866818 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33276302 (View on PubMed)

Other Identifiers

1R01NS084288-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20140056

Identifier Type: -

Identifier Source: org_study_id