A Registry Study of Microcirculation Disorder After Cerebral Small Vessel Disease and Ischemic Stroke

Official title

A Registry Study of Microcirculation Disorder After Cerebral Small Vessel Disease and Ischemic Stroke, MODEST, Research Protocol

Overview

This study aims to construct a registry platform for microcirculatory disorders in a large sample of Chinese patients with cerebral small vessel disease and ischemic stroke; To explore the role of microcirculatory disorders in different types of cerebral small vessel disease and iachemic stroke, as well as their pathogenesis, severity, and prognosis; And to research on the drug treatment of microcirculatory disorders for cerebral small vessel disease and stroke in the real world.

Detailed description

Cerebral small vessel disease (CSVD) is a clinical syndrome with imaging and pathological changes, which is caused by various structural abnormality or functional dysfunction of small blood vessels including cerebral arterioles, perforating arteries, capillaries, and venules. It is also a common cause of stroke. Among people over 60 years old, the prevalence of CSVD exceeds 80%, and it is speculated that the number of CSVD patients in China exceeds 200 million, far higher than the number of stroke patients. CSVD can cause about 20% of stroke and 50% of dementia, while also doubling the risk of dementia and death, and tripling the risk of stroke. It is an important cause of death and disability in elderly people in China.

Stroke is a kind of cerebrovascular diseases characterized by sudden localized or diffuse neurological deficits caused by cerebral blood circulation disorders, and is the main clinical phenotype of cerebrovascular diseases. Stroke is characterized by high incidence rate, high disability rate, high mortality, high recurrence rate, and high economic burden. It is the first cause of death and disability in adult in China.

Microcirculatory disorders may play an important role in the pathophysiological process of ischemic CSVD. The pathological process of CSVD involves various components of the neurovascular units, including the blood-brain barrier composed of vascular endothelial cells, basement membrane, pericytes, and astrocytes, as well as oligodendrocytes, neurons, and extracellular matrix, etc.Among them, the disruption of the blood-brain barrier and endothelial damage are considered to be the initial stage of the pathological process of CSVD, causing the destruction of various secondary microcirculation structures and functions, namely the occurrence of microcirculatory disorders.

Microcirculatory disorders may also play a major role in the occurrence and development of ischemic cerebrovascular disease. By exploring multiple omics markers such as specific molecular biological markers related to ischemic cerebrovascular disease in the pathophysiological pathways of microcirculatory disorders, traditional risk factors and imaging markers can be combined to create prediction models for ineffective reperfusion of acute ischemic stroke and progression of CSVD, providing scientific evidence for improving the prognosis of acute ischemic stroke and CSVD.

Primary outcome measures

• The correlation between microcirculatory disorders and recurrence of stroke (ischemic stroke and hemorrhagic stroke) [Time frame: baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month]
• Correlation between microcirculatory disorders and daily living ability levels (mRS) in patients with acute ischemic stroke [Time frame: baseline, 3rd month, 6th month, 12th month, 18th month, 24th month]
• The correlation between microcirculatory disorders and cognitive function in CSVD (Mini COG). [Time frame: baseline, 3th month, 12th month]

Secondary outcome measures (12)

• The drug treatment of acute ischemic stroke in the real world based on microcirculation disorders. [Time frame: baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month]
• The correlation between microcirculatory disorders and the combination of vascular events (ischemic stroke, hemorrhagic stroke, myocardial infarction, vascular death) in the recovery period of ischemic stroke. [Time frame: baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month]
• The correlation between microcirculatory disorders and the pathogenesis of acute ischemic stroke with different etiological subtypes. [Time frame: baseline, 3rd month, 12th month]
• The correlation between microcirculation disorders and the severity of acute ischemic stroke. [Time frame: baseline, 3rd month, 12th month]
• An effective treatment method for microcirculatory dysfunction targets in acute ischemic stroke. [Time frame: baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month]
• The drug treatment of ischemic stroke in the recovery period based on microcirculation disorders in the real world. [Time frame: baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month]
• The correlation between microcirculatory disorders and the pathogenesis of ischemic stroke during recovery period classified by different etiological subtypes. [Time frame: baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month]
• The correlation between microcirculatory disorders and the severity of ischemic stroke during recovery period. [Time frame: baseline, 3rd month, 12th month]
• An effective treatment method for microcirculatory dysfunction targets in the recovery stage of ischemic stroke. [Time frame: baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month]
• The correlation between microcirculatory disorders and the outcome/prognosis of ischemic stroke during recovery period. [Time frame: baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month]
• The drug treatment of CSVD in the real world based on microcirculation disorders. [Time frame: baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month]
• The correlation between microcirculatory disorders and the pathogenesis of different subtypes of CSVD. [Time frame: baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month]

Eligibility criteria

Inclusion criteria

Study 1:

• Age ≥ 18 years old.
• Acute ischemic stroke within 7 days of onset.
• Sign an informed consent form.

Study 2:

• Age ≥ 18 years old.
• Ischemic stroke during recovery period, within 30 days to 1 year of onset.
• Sign an informed consent form.

Study 3:

• Age ≥ 18 years old.
• Within 3 years, there are characteristic lesions of cerebral small vessel disease on head MRI or CT, and they meet at least one of the following criteria:

• Paraventricular or deep white matter hyperintensities, Fazekas total score ≥ 2;
• Paraventricular or deep white matter hyperintensities, Fazekas total score=1, and at least two vascular risk factors (hypertension, hyperlipidemia, diabetes, current smoking, obesity, history of coronary heart disease, history of stroke).
• Paraventricular or deep white matter hyperintensities, Fazekas total score=1, with ≥ 1 lacune.
• New recent subcortical small infarcts.
• Sign an informed consent form.

Exclusion criteria

Study 1:

• Cerebral hemorrhage and subarachnoid hemorrhage within 3 months of onset.
• There are untreated cerebral vascular malformations or untreated aneurysms (diameter>3mm).
• Confirmed neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Parkinson's syndrome, etc.
• A mental illness diagnosed according to the DSM-V diagnostic criteria.
• There are clear diagnoses of non-vascular white matter lesions, such as multiple sclerosis, adult white matter dysplasia, metabolic encephalopathy, etc.
• Unable to cooperate in completing follow-up visits due to geographical or other reasons.
• The patient also participated in other clinical trials.

Study 2:

• Cerebral hemorrhage and subarachnoid hemorrhage within 3 months of onset.
• There are untreated cerebral vascular malformations or untreated aneurysms (diameter>3mm).
• Confirmed neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Parkinson's syndrome, etc.
• A mental illness diagnosed according to the DSM-V diagnostic criteria.
• There are clear diagnoses of non-vascular white matter lesions, such as multiple sclerosis, adult white matter dysplasia, metabolic encephalopathy, etc.
• Unable to cooperate in completing follow-up visits due to geographical or other reasons.
• The patient also participated in other clinical trials.

Study 3:

• Cerebral hemorrhage and subarachnoid hemorrhage within 3 months of onset.
• There are untreated cerebral vascular malformations or untreated aneurysms (diameter>3mm).
• Confirmed neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Parkinson's syndrome, etc.
• A mental illness diagnosed according to the DSM-V diagnostic criteria.
• There are clear diagnoses of non-vascular white matter lesions, such as multiple sclerosis, adult white matter dysplasia, metabolic encephalopathy, etc.
• Unable to cooperate in completing follow-up visits due to geographical or other reasons.
• The patient also participated in other clinical trials.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model

Cohort

Study locations

China · 1 center

• Beijing Tiantan Hospital — Beijing

Publications

• Chen Weiqi, Pan Yuesong, Chen Xia, Bai Feng, Cao Yongjun, Fan Yuhua, et al. Expert Consensus on Clinical Trial Design Standards for Cerebrovascular Disease Treatment Drugs. Chinese Journal of Stroke.2021;16:288-297
• Hu Wenli, Yang Lei, Li Tingting, Huang Yonghua Consensus of Chinese Experts on the Diagnosis and Treatment of Cerebral small vessel disease 2021. Chinese Journal of Stroke 2021;16:716-726
• van Veluw SJ, Shih AY, Smith EE, Chen C, Schneider JA, Wardlaw JM, Greenberg SM, Biessels GJ. Detection, risk factors, and functional consequences of cerebral microinfarcts. Lancet Neurol. 2017 Sep;16(9):730-740. doi: 10.1016/S1474-4422(17)30196-5. Epub 2017 Jul 14. PMID 28716371
• Debette S, Schilling S, Duperron MG, Larsson SC, Markus HS. Clinical Significance of Magnetic Resonance Imaging Markers of Vascular Brain Injury: A Systematic Review and Meta-analysis. JAMA Neurol. 2019 Jan 1;76(1):81-94. doi: 10.1001/jamaneurol.2018.3122. PMID 30422209
• Compilation team of the
• De Silva TM, Faraci FM. Contributions of Aging to Cerebral Small Vessel Disease. Annu Rev Physiol. 2020 Feb 10;82:275-295. doi: 10.1146/annurev-physiol-021119-034338. Epub 2019 Oct 16. PMID 31618600
• Cuadrado-Godia E, Dwivedi P, Sharma S, Ois Santiago A, Roquer Gonzalez J, Balcells M, Laird J, Turk M, Suri HS, Nicolaides A, Saba L, Khanna NN, Suri JS. Cerebral Small Vessel Disease: A Review Focusing on Pathophysiology, Biomarkers, and Machine Learning Strategies. J Stroke. 2018 Sep;20(3):302-320. doi: 10.5853/jos.2017.02922. Epub 2018 Sep 30. PMID 30309226
• Ter Telgte A, van Leijsen EMC, Wiegertjes K, Klijn CJM, Tuladhar AM, de Leeuw FE. Cerebral small vessel disease: from a focal to a global perspective. Nat Rev Neurol. 2018 Jul;14(7):387-398. doi: 10.1038/s41582-018-0014-y. PMID 29802354

Identifiers

NCT: NCT06077305 · KY2023-049-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗