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

Ischemic Stroke Clinical Trial

— MODEST  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06077305
• Other study ID #: KY2023-049-01
• Status: Not yet recruiting
• Start date: October 30, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: October 2023
• Source: Beijing Tiantan Hospital
• Contact: Yilong Wang, PhD+MD
• Phone: 0086-010-67092222
• Email: yilong528[@]aliyun.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20000
• Est. completion date: December 31, 2026
• Est. primary completion date: October 31, 2026
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Study 1:

1. Age = 18 years old.

2. Acute ischemic stroke within 7 days of onset.

3. Sign an informed consent form.

Study 2:

1. Age = 18 years old.

2. Ischemic stroke during recovery period, within 30 days to 1 year of onset.

3. Sign an informed consent form.

Study 3:

1. Age = 18 years old.

2. 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:

1. Paraventricular or deep white matter hyperintensities, Fazekas total score = 2;

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).

3. Paraventricular or deep white matter hyperintensities, Fazekas total score=1, with = 1 lacune.

4. New recent subcortical small infarcts.

3. Sign an informed consent form. Exclusion Criteria:

Study 1:

1. Cerebral hemorrhage and subarachnoid hemorrhage within 3 months of onset.

2. There are untreated cerebral vascular malformations or untreated aneurysms (diameter>3mm).

3. Confirmed neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Parkinson's syndrome, etc.

4. A mental illness diagnosed according to the DSM-V diagnostic criteria.

5. There are clear diagnoses of non-vascular white matter lesions, such as multiple sclerosis, adult white matter dysplasia, metabolic encephalopathy, etc.

6. Unable to cooperate in completing follow-up visits due to geographical or other reasons.

7. The patient also participated in other clinical trials.

Study 2:

1. Cerebral hemorrhage and subarachnoid hemorrhage within 3 months of onset.

2. There are untreated cerebral vascular malformations or untreated aneurysms (diameter>3mm).

3. Confirmed neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Parkinson's syndrome, etc.

4. A mental illness diagnosed according to the DSM-V diagnostic criteria.

5. There are clear diagnoses of non-vascular white matter lesions, such as multiple sclerosis, adult white matter dysplasia, metabolic encephalopathy, etc.

6. Unable to cooperate in completing follow-up visits due to geographical or other reasons.

7. The patient also participated in other clinical trials.

Study 3:

1. Cerebral hemorrhage and subarachnoid hemorrhage within 3 months of onset.

2. There are untreated cerebral vascular malformations or untreated aneurysms (diameter>3mm).

3. Confirmed neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Parkinson's syndrome, etc.

4. A mental illness diagnosed according to the DSM-V diagnostic criteria.

5. There are clear diagnoses of non-vascular white matter lesions, such as multiple sclerosis, adult white matter dysplasia, metabolic encephalopathy, etc.

6. Unable to cooperate in completing follow-up visits due to geographical or other reasons.

7. The patient also participated in other clinical trials.

Related Conditions & MeSH terms

• Cerebral Infarction
• Cerebral Small Vessel Diseases
• Ischemia
• Ischemic Stroke
• Stroke

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital

Country where clinical trial is conducted

China, 

References & Publications (23)

Amki ME, Wegener S. Reperfusion failure despite recanalization in stroke: New translational evidence. Clinical and Translational Neuroscience. 2021;5:2514183X2110071

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

Compilation team of the

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 — View Citation

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. — View Citation

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 — View Citation

Diaz-Otero JM, Fisher C, Downs K, Moss ME, Jaffe IZ, Jackson WF, Dorrance AM. Endothelial Mineralocorticoid Receptor Mediates Parenchymal Arteriole and Posterior Cerebral Artery Remodeling During Angiotensin II-Induced Hypertension. Hypertension. 2017 Dec — View Citation

Feng CM, Narayana S, Lancaster JL, Jerabek PA, Arnow TL, Zhu F, Tan LH, Fox PT, Gao JH. CBF changes during brain activation: fMRI vs. PET. Neuroimage. 2004 May;22(1):443-6. doi: 10.1016/j.neuroimage.2004.01.017. — View Citation

Han JY, Li Q, Ma ZZ, Fan JY. Effects and mechanisms of compound Chinese medicine and major ingredients on microcirculatory dysfunction and organ injury induced by ischemia/reperfusion. Pharmacol Ther. 2017 Sep;177:146-173. doi: 10.1016/j.pharmthera.2017.0 — View Citation

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

Hussein HM, Georgiadis AL, Vazquez G, Miley JT, Memon MZ, Mohammad YM, Christoforidis GA, Tariq N, Qureshi AI. Occurrence and predictors of futile recanalization following endovascular treatment among patients with acute ischemic stroke: a multicenter stu — View Citation

Hussein HM, Saleem MA, Qureshi AI. Rates and predictors of futile recanalization in patients undergoing endovascular treatment in a multicenter clinical trial. Neuroradiology. 2018 May;60(5):557-563. doi: 10.1007/s00234-018-2016-2. Epub 2018 Mar 25. — View Citation

Iadecola C, Buckwalter MS, Anrather J. Immune responses to stroke: mechanisms, modulation, and therapeutic potential. J Clin Invest. 2020 Jun 1;130(6):2777-2788. doi: 10.1172/JCI135530. — View Citation

Litak J, Mazurek M, Kulesza B, Szmygin P, Litak J, Kamieniak P, Grochowski C. Cerebral Small Vessel Disease. Int J Mol Sci. 2020 Dec 20;21(24):9729. doi: 10.3390/ijms21249729. — View Citation

Low A, Mak E, Rowe JB, Markus HS, O'Brien JT. Inflammation and cerebral small vessel disease: A systematic review. Ageing Res Rev. 2019 Aug;53:100916. doi: 10.1016/j.arr.2019.100916. Epub 2019 Jun 10. — View Citation

Montenont E, Rondina MT, Campbell RA. Altered functions of platelets during aging. Curr Opin Hematol. 2019 Sep;26(5):336-342. doi: 10.1097/MOH.0000000000000526. — View Citation

Ng FC, Coulton B, Chambers B, Thijs V. Persistently Elevated Microvascular Resistance Postrecanalization. Stroke. 2018 Oct;49(10):2512-2515. doi: 10.1161/STROKEAHA.118.021631. — View Citation

Reis PA, Alexandre PCB, D'Avila JC, Siqueira LD, Antunes B, Estato V, Tibirica EV, Verdonk F, Sharshar T, Chretien F, Castro-Faria-Neto HC, Bozza FA. Statins prevent cognitive impairment after sepsis by reverting neuroinflammation, and microcirculatory/en — View Citation

Shi Y, Thrippleton MJ, Makin SD, Marshall I, Geerlings MI, de Craen AJM, van Buchem MA, Wardlaw JM. Cerebral blood flow in small vessel disease: A systematic review and meta-analysis. J Cereb Blood Flow Metab. 2016 Oct;36(10):1653-1667. doi: 10.1177/02716 — View Citation

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. — View Citation

Uemura MT, Maki T, Ihara M, Lee VMY, Trojanowski JQ. Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia. Front Aging Neurosci. 2020 Apr 14;12:80. doi: 10.3389/fnagi.2020.00080. eCollection 2020. — View Citation

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 2 — View Citation

Xiao Siting, Cao Chunran, Liu Hongyan, Gao Xiaoxin, Sun Yuanyuan, Zhao Jinyan, et al. Progress in pharmaceutical research on Ginkgo biloba leaf extract China Pharmaceutical. 2022;36:429-443

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The correlation between microcirculatory disorders and recurrence of stroke (ischemic stroke and hemorrhagic stroke)	This study will collect disease information related to microcirculatory disorders and recurrent stroke among patients with acute ischemic stroke.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month
Primary	Correlation between microcirculatory disorders and daily living ability levels (mRS) in patients with acute ischemic stroke	This study will collect disease information related to microcirculatory disorders and mRS among ischemic stroke patients during recovery period.	baseline, 3rd month, 6th month, 12th month, 18th month, 24th month
Primary	The correlation between microcirculatory disorders and cognitive function in CSVD (Mini COG).	This study will collect disease information related to microcirculatory disorders and Mini COG among patients with CSVD.	baseline, 3th month, 12th month
Secondary	The drug treatment of acute ischemic stroke in the real world based on microcirculation disorders.	Record all the medication treatment information during the follow-up period since the last visit, and all the medications information is collated to describe the patient's medication regimen.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month
Secondary	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.	This study will collect Major Adverse Cardiovascular Events (MACE): including ischemic stroke, hemorrhagic stroke, myocardial infarction, and vascular death.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month
Secondary	The correlation between microcirculatory disorders and the pathogenesis of acute ischemic stroke with different etiological subtypes.	Record the final diagnosis and main combined diagnosis of this enrollment event and complete blood laboratory examination, transcranial doppler ultrasound examination, physical examination and the like to ensure and evaluate the correlation between microcirculatory disorders and the pathogenesis of recovery ischemic stroke in different etiological subtypes.	baseline, 3rd month, 12th month
Secondary	The correlation between microcirculation disorders and the severity of acute ischemic stroke.	This study will collect disease information related to microcirculatory disorders among patients with acute ischemic stroke to evaluate the correlation between microcirculation disorders and the severity of acute ischemic stroke.	baseline, 3rd month, 12th month
Secondary	An effective treatment method for microcirculatory dysfunction targets in acute ischemic stroke.	Record the medication treatment information during the follow-up period since the last visit, to explore and build an effective treatment method for microcirculatory dysfunction targets in acute ischemic stroke.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month
Secondary	The drug treatment of ischemic stroke in the recovery period based on microcirculation disorders in the real world.	Record the medication treatment information during the follow-up period since the last visit, including antiplatelet therapy, antihypertensive therapy, lipid-lowering, hypoglycemic, vasoactive drugs, neuroprotective agents, traditional Chinese medicine, etc. Detailed records of medication types, daily dosage, and duration are required.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month
Secondary	The correlation between microcirculatory disorders and the pathogenesis of ischemic stroke during recovery period classified by different etiological subtypes.	Record the final diagnosis and main combined diagnosis of this enrollment event and complete blood laboratory examination, transcranial doppler ultrasound examination, physical examination and the like to ensure and evaluate the correlation between microcirculatory disorders and the pathogenesis of recovery ischemic stroke in different etiological subtypes.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month
Secondary	The correlation between microcirculatory disorders and the severity of ischemic stroke during recovery period.	This study will collect disease information related to microcirculatory disorders and ischemic stroke patients during recovery period to evaluate the correlation between microcirculation disorders and the severity of ischemic stroke.	baseline, 3rd month, 12th month
Secondary	An effective treatment method for microcirculatory dysfunction targets in the recovery stage of ischemic stroke.	Record the medication treatment information during the follow-up period since the last visit, to explore and build an effective treatment method for microcirculatory dysfunction targets in the recovery stage of ischemic stroke.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month
Secondary	The correlation between microcirculatory disorders and the outcome/prognosis of ischemic stroke during recovery period.	This study will collect disease information related to microcirculatory disorders and mRS among ischemic stroke patients during recovery period to assess the correlation between microcirculatory disorders and the outcome/prognosis of ischemic stroke during recovery period.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month
Secondary	The drug treatment of CSVD in the real world based on microcirculation disorders.	Record the medication treatment information during the follow-up period since the last visit, including antiplatelet therapy, antihypertensive therapy, lipid-lowering, hypoglycemic, vasoactive drugs, neuroprotective agents, traditional Chinese medicine, etc. Detailed records of medication types, daily dosage, and duration are required.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month
Secondary	The correlation between microcirculatory disorders and the pathogenesis of different subtypes of CSVD.	Record the final diagnosis and main combined diagnosis of this enrollment event and complete blood laboratory examination, transcranial doppler ultrasound examination, physical examination and the like to ensure and evaluate the correlation between microcirculatory disorders and the pathogenesis of different subtypes of CSVD.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month
Secondary	The correlation between microcirculatory disorders and the severity of CSVD.	This study will collect disease information related to microcirculatory disorders and CSVD to evaluate the correlation between microcirculation disorders and the severity of CSVD.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month
Secondary	Effective treatment methods for microcirculatory disorders in CSVD.	Record the medication treatment information during the follow-up period since the last visit, to explore and build an effective treatment method for microcirculatory dysfunction targets in the CSVD.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month
Secondary	The correlation between microcirculatory disorders and clinical symptoms of CSVD.	This study will complete and collect relevant information of clinical symptoms and microcirculatory disorders among patients with CSVD.	baseline, 14th day, 3rd month, 6th month, 12th month, 18th month, 24th month