Clinical trial NCT02719652: Vessel Wall and Perfusion Imaging in Intracranial Atherosclerosis
Official title: Vessel Wall and Perfusion Imaging in Intracranial Atherosclerosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Intracranial Atherosclerosis
Keywords: intracranial atherosclerotic disease（ICAD）
vulnerable plaque
high-resolution magnetic resonance imaging （HR-MRI）
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2016-03-25
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants with significant MCA stenosis（≥50%）on TCD, MRA, and/or CTA together with one or more risk factors of atherosclerosis will be prospectively recruited. Symtomatic patients will be included if they had suffered from a recent transient ischemic attack or ischemic stroke(NHISS≤6) in the territory of the stenotic MCA. Asymptomatic patients will be included if they had no history of cerebrovascular events or a history of an ischemic event in a territory outside that the affected MCA.

Brief summary: Intracranial atherosclerotic disease (ICAD) is an important cause of ischemic stroke. The occurrence of stroke caused by symptomatic ICAD is significantly different compared with asymptomatic ICAD (19% vs 3.5%), suggesting that plaque vulnerability may be responsible for the difference. Based on the previous high-resolution magnetic resonance vessel wall imaging (HR-MRI) results, the investigators hypothesis that the feature of intracranial plaque enhancement is an important imaging biomarker of plaque instability, which is closely related to stroke. The investigators will establish the ICAD cohort and use HR-MRI to investigate the composition, morphology and the enhancement pattern of symptomatic ICAD plaques. These findings will correlate with biochemical markers, and stroke recurrence, in order to explore:

1. plaque characteristics and the enhancement features between symptomatic ICAD and asymptomatic ICAD
2. the relationship between plaque enhancement and the composition of plaques;
3. relationship among enhancement features of symptomatic ICAD plaques, biomarkers with different clinical significance,
4. evolution of enhancement features of symptomatic ICAD plaques under intensive medical therapy.

The investigators aim to explore the correlation between vulnerable plaque stratification and clinical outcomes, to explore the value of vascular responses in the pathogenicity of ICAD vulnerable plaques, as well as to provide objective basis for the establishment of the evaluation criteria of intracranial atherosclerotic vulnerable plaques.

Detailed description: Detailed description:

Title: Vessel wall and Perfusion Imaging in Intracranial Atherosclerosis

Design: This is an prospective study that will study the characteristics of intracranial atherosclerotic plaque and the enhancement features of symptomatic ICAD during a mean follow-up of 1 year in symptomatic or asymtomatic patients with moderate to severe stenosis of middle cerebral artery(MCA).

In the WASID trail,patients with at least 70% stenosis of a major intracranial artery had an increased risk of recurrent stroke. However,The degree of stenosis is no longer the single predictor of vulnerable atherosclerotic lesions. Vulnerable plaques are closely associated with stroke recurrence.With the development of neurologic imaging, HR-MRI has unique ability to provide information on plaque compositions, plaque burden and vulnerable features. Several recent investigations suggest that enhancement of intracranial plaque is associated with recurrent stroke. However, no corhort study has been performed.

This prospective, multicenter trail will be conducted in China. Based on the previous work,participants will be divided into two groups :symtomatic ICAD and asymtomatic ICAD. Neurological examination and clinical sera testing will be performed at baseline, 1 month, 3 months, 6 months, and 12 months.The stroke incidence rate of asymptomatic ICAD and stroke recurrence rate of symptomatic ICAD will be recorded.

Eligibility criteria: Inclusion Criteria:

* Symptomatic patients who suffered TIA or non-severe ischemic stroke(NHISS ≤6) in one week with 50% to 90% stenosis of MCA.
* Asymptomatic patients with ≥50% MCA stenosis without history of cerebrovascular events or an ischemic event in a territory outside that supplied by the affected MCA.
* Degree of ≥50% stenosis must be conformed by MRA, CTA and/or TCD.
* Age: 18-80 years.
* mRS scale score of ≤2.
* Patients who agree with future follow-up visits.
* Patients who sign the informed consent.

Exclusion Criteria:

* Coexistent ipsilateral internal carotid stenosis（≥50%）on MRA, CTA and/or TCD. Non-atherosclerotic vasculopathy, such as dissection, vasculitis,or moyamoya disease.
* Evidence of cardioembolism, such as atrial fibrillation, mechanical prosthetic valve disease, sick sinus syndrome, dilated cardiomyopathy, left ventricular thrombus, or recent myocardial infarction, hemorrhage, watershed infarction, or other cerebral diseases, such as vascular malformation, neoplasms, and encephalopyosis.
* Patients who are unable to undergo HR-MRI owing to underlying medical conditions.
* Patients who are allergic to any of the study medications, including aspirin, clopidogrel,atorvastatin,or rosuvastatin.

Primary outcomes:
measure: Stroke recurrence
timeFrame: 1 year
Secondary outcomes:
measure: Death
timeFrame: 1 year
measure: Any stroke, severe transient ischemic attack (TIA) outside the territory of symptomatic MCA
timeFrame: at 7 days, 30 days,3 months，6 months, 12 months
measure: Stroke of asymptomatic participants
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Neurology, Xuanwu hospital
state: Beijing
Study officials:
affiliation: Xuanwu Hospital, Capital Medical University, Beijing, China
name: Guo Xiuhai, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Xuanwu Hospital, Capital Medical University, Beijing, China
name: Qi Yang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mossa-Basha M, Hwang WD, De Havenon A, Hippe D, Balu N, Becker KJ, Tirschwell DT, Hatsukami T, Anzai Y, Yuan C. Multicontrast high-resolution vessel wall magnetic resonance imaging and its value in differentiating intracranial vasculopathic processes. Stroke. 2015 Jun;46(6):1567-73. doi: 10.1161/STROKEAHA.115.009037. Epub 2015 May 7.
citation: Ahn SH, Lee J, Kim YJ, Kwon SU, Lee D, Jung SC, Kang DW, Kim JS. Isolated MCA disease in patients without significant atherosclerotic risk factors: a high-resolution magnetic resonance imaging study. Stroke. 2015 Mar;46(3):697-703. doi: 10.1161/STROKEAHA.114.008181. Epub 2015 Jan 27.
citation: Ryoo S, Cha J, Kim SJ, Choi JW, Ki CS, Kim KH, Jeon P, Kim JS, Hong SC, Bang OY. High-resolution magnetic resonance wall imaging findings of Moyamoya disease. Stroke. 2014 Aug;45(8):2457-60. doi: 10.1161/STROKEAHA.114.004761. Epub 2014 Jun 19.
citation: Holmstedt CA, Turan TN, Chimowitz MI. Atherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and treatment. Lancet Neurol. 2013 Nov;12(11):1106-14. doi: 10.1016/S1474-4422(13)70195-9.
citation: Vakil P, Vranic J, Hurley MC, Bernstein RA, Korutz AW, Habib A, Shaibani A, Dehkordi FH, Carroll TJ, Ansari SA. T1 gadolinium enhancement of intracranial atherosclerotic plaques associated with symptomatic ischemic presentations. AJNR Am J Neuroradiol. 2013 Dec;34(12):2252-8. doi: 10.3174/ajnr.A3606. Epub 2013 Jul 4.