Ischemic Stroke, AcuteNCT05585255
Clinical Significance of DKK2 Protein in Cerebral Ischemia-reperfusion Injury
An observational study of Ischemic Stroke, Acute and Ischemia-reperfusion Injury, run by Nanfang Hospital, Southern Medical University at 2 sites in China.
Trial summary
The study is a two-center prospective cohort clinical trial. The primary purpose of this trial is to identify the pattern of DKK2 serum levels in ischemic stroke patients after revascularization therapy and determine the correlation between serum DKK2 levels and prognosis. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Ischemic Stroke, Acute, Ischemia-reperfusion Injury, Cerebral Edema
- What is being tested?
- enzyme-linked immunosorbent assay(ELISA)
- How many people
- 108 participants
- Where
- 2 sitesChina
- Study dates
- 1 Sep 2022to 30 Sep 2024
- How long will I take part?
- 90 Days
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Acute ischemic stroke patients with large vessel occlusion who are treated with mechanical embolization and successfully revascularized at Dongguan Hospital of Southern Medical University and Nanfang Hospital of Southern Medical University.
Who may be able to join
- Age ≥ 18 years, < 80 years, sex not limited;
- Definite clinical diagnosis of acute ischemic stroke;
- Baseline NIHSS score ≥ 6 and ≤ 25;
- CTA/MRA/DSA examination suggests large vessel occlusion in the anterior circulation (internal carotid artery, M1/M2 segment of the middle cerebral artery);
- The criteria for receiving endovascular treatment in accordance with the Chinese Guidelines for Early Endovascular Intervention in Acute Ischemic Stroke 2018 and have successful revascularization (TICI ≥ grade 2b);
- Subjects or their legal representatives agree to the treatment and sign the informed consent form.
Who cannot join
- Patients with combined posterior circulation infarction;
- The mRS ≥ 2 points before the current episode;
- Patients who are to be treated with or have been treated with anticoagulants;
- Patients with existing or active organ bleeding within 6 months of enrollment, including cerebral hemorrhage, subarachnoid hemorrhage, gastrointestinal tract hemorrhage, fundus hemorrhage, etc;
- The presence of other intracranial pathologies, such as cerebrovascular malformations, cerebral venous lesions, tumors, and other diseases involving the cranium;
- Severe organ dysfunction or failure;
Show all 12Show fewer
- Those with severe hematologic disorders or severe coagulation abnormalities；
- Those with a history of severe trauma or major surgical procedures within 6 months prior to enrollment;
- Pregnant or lactating women;
- Patients with a life expectancy of less than 3 months or who for other reasons are unable to complete the study;
- Unwillingness to be followed up or poor compliance with treatment;
- Other conditions that the investigator considers unsuitable for enrollment.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
Dongguan Hospital of Southern Medical University
Dongguan, Guangdong, 523059
Zhu Shi, PHD, 0769-22679351, shizhu@smu.edu.cn
- Recruiting
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, 510515
Kaibin Huang, PHD, (+86) 020-62787664, hkb@smu.edu.cn
About this study
Official title: Clinical Significance, Mechanism of Action, and New Targeted Drug Research of DKK2 Protein in Cerebral Ischemia-reperfusion Injury
The study is a two-center prospective cohort clinical trial. The primary purpose of this trial is to identify the pattern of DKK2 serum levels in ischemic stroke patients after revascularization therapy and determine the correlation between serum DKK2 levels and prognosis.
Read the detailed description
Ischemic stroke refers to ischaemic and hypoxic necrosis of brain tissue caused by narrowing or occlusion of the blood vessels in the brain and accounts for approximately 80% of all strokes. It is characterized by high morbidity, mortality, disability, and recurrence rates. Reperfusion is currently the most effective treatment for the acute phase of ischaemic stroke, including pharmacological thrombolysis and mechanical embolization. Although successful revascularization can reperfuse areas of cerebral ischemia, it can cause acute cerebrovascular damage while restoring blood supply to brain tissue, leading to disruption of the blood-brain barrier (BBB), increased risk of cerebral edema and hemorrhagic transformation, and increased inflammation of neural tissue, which can further damage brain tissue. Targeted reduction of endothelial damage from ischemia-reperfusion will therefore effectively protect neurons from subsequent damage, thereby minimizing neurological impairment after stroke and maximizing the benefit of revascularisation therapy.
The Wnt signaling pathway has been identified by several research groups worldwide as a key regulatory pathway in the maintenance of cerebrovascular and neural cell function. The DKK (Dickkopf-related protein) family of proteins is the most representative group of classical Wnt signaling pathway inhibitors. DKK proteins competitively bind to the Wnt co-receptor LRP5/6, thereby inhibiting the activity of Wnt proteins and exerting their inhibitory effects on the Wnt/β-catenin signaling pathway. We initially found that DKK2 serum levels increased significantly after 4.5 h of recanalization therapy in 20 patients with large vessel occlusive acute stroke, and decreased after 24 h. Increased DKK2 levels were strongly associated with an unfavorable prognosis. This was corroborated in animal models as well, DKK2 expression levels in ischaemic brain tissue and peripheral blood were both significantly elevated and rapidly upregulated within 6-12 h of the onset of cerebral ischemia-reperfusion in mice. In vitro cellular assays showed that DKK2 protein significantly inhibited the activity of the Wnt/β-catenin signaling pathway. We further study showed that upregulation of DKK2 protein levels in the blood of mice by intravenous administration of adenovirus expressing DKK2 protein significantly increased cerebral infarction and neurological impairment in mice with stroke. The increased expression of DKK2 protein in brain tissue is the main reason for the downregulation of Wnt/β-catenin signaling pathway activity after ischemia/reperfusion, which leads to blood-brain barrier damage, neuronal cell death, and neuroinflammation, and ultimately promotes brain tissue damage and neurological dysfunction. It is a new target for drug therapy and has great scientific significance and clinical application prospects.
This clinical study is conducted at Dongguan Hospital of Southern Medical University and Nanfang Hospital of Southern Medical University. Acute ischemic stroke patients with large vessel occlusion who received mechanical thrombectomy therapy and are successfully revascularized will be included and followed up for 90 d, along with testing serum levels of DKK2 protein to explore its correlation with the prognosis of enrolled patients. Venous blood samples will be collected before, and 24 h, 48 h, and 72 h after revascularization treatment in enrolled patients. Venous blood samples will be collected before and 0h, 24 h, 48 h, and 72 h after revascularisation treatment to test serum KKD2 level, and cranial CT examination will be performed before, 24 h, and 72 h after revascularization treatment to detect the occurrence of the transformation of hemorrhage, the severity of cerebral edema, and midline shift after revascularisation treatment. Blood-brain barrier injury-related indicators (MMP-9, ICAM-1) and inflammation-related indicators (IL-6, IL-1β, TNF-α, IL-10) will be measured at each time point of DKK2 testing. NIHSS scores will be evaluated before, 0h (immediately after revascularization treatment), 24 h, 48 h, 72 h, and 7 d after revascularization treatment. The mRS scores will be followed up at 30 days and 90 days after the onset to clarify the relationship between serum DKK2 levels and large vessel occlusion. We aim to investigate the mechanism of DKK2 causing adverse clinical outcomes such as BBB leakage, cerebral edema, and hemorrhagic transformation at a real-world clinical level by collecting blood samples, clinical follow-up, and neurological scoring from stroke patients by measuring DKK2 levels and brain imaging parameters for quantitative assessment.
- Being tested
- enzyme-linked immunosorbent assay(ELISA)
- Medical subject headings
- Ischemic Stroke, Reperfusion Injury, Brain Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enzyme-linked immunosorbent assay(ELISA)Diagnostic test
After allowing to stand at room temperature for 2h, blood samples are centrifuged at 4 ℃ for 15 min (12000 rpm) to collect the supernatant. Then, the levels of DKK2, IL-6, IL-1β, TNF-α, and IL-10 in the supernatants are tested by ELISA detection.
| Study group | Role | What they receive |
|---|---|---|
| Acute ischemic stroke patients | Acute ischemic stroke patients with large vessel occlusion who received mechanical thrombectomy therapy and are successfully revascularized Receives: Diagnostic Test: enzyme-linked immunosorbent assay(ELISA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
90-day Functional Outcome.
The favorable prognosis (modified Rankin score [mRS] score ≤ 2) and the unfavorable prognosis group ([mRS] score ≥ 3) within 90 d after onset.
Measured: The mRS score will follow up at 90 days.
Secondary outcomes (5)
Incidence of neurological deterioration
Significantly improved NIHSS score (an increase in the NIHSS score by ≥4 points) within 7 days after onset.
Measured: The NIHSS score will evaluat at the point before revascularization treatment, 0 (immediately after revascularization treatment), 24, 48, 72 hours, and 7 days after revascularization treatment.
Incidence of substantial hemorrhagic transformation
Cranial CT examination will perform to detect substantial hemorrhagic transformation (ECASS typing PH2 type) within 72 hours.
Measured: At the point before revascularization treatment, 24, and 72 hours after revascularization treatment.
The severity of cerebral edema.
Cranial CT examination will perform to detect the varying severity of cerebral edema groups (divided into 3 groups according to CED scores 1, 2 and 3) within 72 hours.
Measured: At the point before revascularization treatment, 24, and 72 hours after revascularization treatment.
Incidence of midline shift ≥ 6mm.
Cranial CT examination will perform to detect the severity of cerebral edema and cerebral hernia.
Measured: At the point before revascularization treatment, 24, and 72 hours after revascularization treatment.
Levels of major inflammatory indicators in peripheral blood.
Blood-brain barrier injury-related indicators (MMP-9, ICAM-1) and inflammation-related indicators (IL-6, IL-1β, TNF-α, IL-10).
Measured: Before revascularization treatment, 24, 48, 72 hours and 7 days after revascularization treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2022
- Study start1 Sep 2022
- Primary completion30 Sep 2024 (estimated)
- Study completion30 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Ischemic Stroke, AcuteStudies of the same condition, open and under way.
- More trials run by Nanfang Hospital, Southern Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 108 participants (estimated)
- Target duration
- 90 Days
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Huang Kaibin, Nanfang Hospital, Southern Medical University
- Investigators
- Zhu Shi, PHD, Study chair, Dongguan Hospital of Southern Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05585255
- Sponsor's protocol ID
- NFEC-2022-273
- Status last verified
- Mar 2024
- First submitted
- 21 Sep 2022
- Last updated
- 25 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The study is proceeding.
Publications
GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 May;18(5):439-458. doi: 10.1016/S1474-4422(19)30034-1. Epub 2019 Mar 11.
PubMed 30871944Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, Li X, Wang L, Wang L, Liu Y, Liu J, Zhang M, Qi J, Yu S, Afshin A, Gakidou E, Glenn S, Krish VS, Miller-Petrie MK, Mountjoy-Venning WC, Mullany EC, Redford SB, Liu H, Naghavi M, Hay SI, Wang L, Murray CJL, Liang X. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2019 Sep 28;394(10204):1145-1158. doi: 10.1016/S0140-6736(19)30427-1. Epub 2019 Jun 24.
PubMed 31248666Phipps MS, Cronin CA. Management of acute ischemic stroke. BMJ. 2020 Feb 13;368:l6983. doi: 10.1136/bmj.l6983.
PubMed 32054610Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, Kleinig TJ, Wijeratne T, Curtze S, Dewey HM, Miteff F, Tsai CH, Lee JT, Phan TG, Mahant N, Sun MC, Krause M, Sturm J, Grimley R, Chen CH, Hu CJ, Wong AA, Field D, Sun Y, Barber PA, Sabet A, Jannes J, Jeng JS, Clissold B, Markus R, Lin CH, Lien LM, Bladin CF, Christensen S, Yassi N, Sharma G, Bivard A, Desmond PM, Yan B, Mitchell PJ, Thijs V, Carey L, Meretoja A, Davis SM, Donnan GA; EXTEND Investigators. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Engl J Med. 2019 May 9;380(19):1795-1803. doi: 10.1056/NEJMoa1813046.
PubMed 31067369Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, Palesch YY, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG; DEFUSE 3 Investigators. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018 Feb 22;378(8):708-718. doi: 10.1056/NEJMoa1713973. Epub 2018 Jan 24.
PubMed 29364767Patel P, Yavagal D, Khandelwal P. Hyperacute Management of Ischemic Strokes: JACC Focus Seminar. J Am Coll Cardiol. 2020 Apr 21;75(15):1844-1856. doi: 10.1016/j.jacc.2020.03.006.
PubMed 32299596Yang P, Zhang Y, Zhang L, Zhang Y, Treurniet KM, Chen W, Peng Y, Han H, Wang J, Wang S, Yin C, Liu S, Wang P, Fang Q, Shi H, Yang J, Wen C, Li C, Jiang C, Sun J, Yue X, Lou M, Zhang M, Shu H, Sun D, Liang H, Li T, Guo F, Ke K, Yuan H, Wang G, Yang W, Shi H, Li T, Li Z, Xing P, Zhang P, Zhou Y, Wang H, Xu Y, Huang Q, Wu T, Zhao R, Li Q, Fang Y, Wang L, Lu J, Li Y, Fu J, Zhong X, Wang Y, Wang L, Goyal M, Dippel DWJ, Hong B, Deng B, Roos YBWEM, Majoie CBLM, Liu J; DIRECT-MT Investigators. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. N Engl J Med. 2020 May 21;382(21):1981-1993. doi: 10.1056/NEJMoa2001123. Epub 2020 May 6.
PubMed 32374959Moskowitz MA, Lo EH, Iadecola C. The science of stroke: mechanisms in search of treatments. Neuron. 2010 Jul 29;67(2):181-98. doi: 10.1016/j.neuron.2010.07.002.
PubMed 20670828Shi K, Zou M, Jia DM, Shi S, Yang X, Liu Q, Dong JF, Sheth KN, Wang X, Shi FD. tPA Mobilizes Immune Cells That Exacerbate Hemorrhagic Transformation in Stroke. Circ Res. 2021 Jan 8;128(1):62-75. doi: 10.1161/CIRCRESAHA.120.317596. Epub 2020 Oct 19.
PubMed 33070717Wang R, Zhu Y, Liu Z, Chang L, Bai X, Kang L, Cao Y, Yang X, Yu H, Shi MJ, Hu Y, Fan W, Zhao BQ. Neutrophil extracellular traps promote tPA-induced brain hemorrhage via cGAS in mice with stroke. Blood. 2021 Jul 8;138(1):91-103. doi: 10.1182/blood.2020008913.
PubMed 33881503El-Benna J, Hurtado-Nedelec M, Marzaioli V, Marie JC, Gougerot-Pocidalo MA, Dang PM. Priming of the neutrophil respiratory burst: role in host defense and inflammation. Immunol Rev. 2016 Sep;273(1):180-93. doi: 10.1111/imr.12447.
PubMed 27558335Chen R, Zhang X, Gu L, Zhu H, Zhong Y, Ye Y, Xiong X, Jian Z. New Insight Into Neutrophils: A Potential Therapeutic Target for Cerebral Ischemia. Front Immunol. 2021 Jul 14;12:692061. doi: 10.3389/fimmu.2021.692061. eCollection 2021.
PubMed 34335600Jian Z, Liu R, Zhu X, Smerin D, Zhong Y, Gu L, Fang W, Xiong X. The Involvement and Therapy Target of Immune Cells After Ischemic Stroke. Front Immunol. 2019 Sep 11;10:2167. doi: 10.3389/fimmu.2019.02167. eCollection 2019.
PubMed 31572378O'Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW. 1,026 experimental treatments in acute stroke. Ann Neurol. 2006 Mar;59(3):467-77. doi: 10.1002/ana.20741.
PubMed 16453316Zhou Z, Lu J, Liu WW, Manaenko A, Hou X, Mei Q, Huang JL, Tang J, Zhang JH, Yao H, Hu Q. Advances in stroke pharmacology. Pharmacol Ther. 2018 Nov;191:23-42. doi: 10.1016/j.pharmthera.2018.05.012. Epub 2018 May 25.
PubMed 29807056
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Significance, Mechanism of Action, and New Targeted Drug Research of DKK2 Protein in Cerebral Ischemia-reperfusion Injury
- ClinicalTrials.gov ID
- NCT05585255
- Acronym / sponsor ID
- NFEC-2022-273
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- Nanfang Hospital, Southern Medical UniversityUniversity, hospital or other
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 30 Sep 2024 (estimated)
- First posted
- 18 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a two-center prospective cohort clinical trial. The primary purpose of this trial is to identify the pattern of DKK2 serum levels in ischemic stroke patients after revascularization therapy and determine the correlation between serum DKK2 levels and prognosis.
Detailed description
Ischemic stroke refers to ischaemic and hypoxic necrosis of brain tissue caused by narrowing or occlusion of the blood vessels in the brain and accounts for approximately 80% of all strokes. It is characterized by high morbidity, mortality, disability, and recurrence rates. Reperfusion is currently the most effective treatment for the acute phase of ischaemic stroke, including pharmacological thrombolysis and mechanical embolization. Although successful revascularization can reperfuse areas of cerebral ischemia, it can cause acute cerebrovascular damage while restoring blood supply to brain tissue, leading to disruption of the blood-brain barrier (BBB), increased risk of cerebral edema and hemorrhagic transformation, and increased inflammation of neural tissue, which can further damage brain tissue. Targeted reduction of endothelial damage from ischemia-reperfusion will therefore effectively protect neurons from subsequent damage, thereby minimizing neurological impairment after stroke and maximizing the benefit of revascularisation therapy.
The Wnt signaling pathway has been identified by several research groups worldwide as a key regulatory pathway in the maintenance of cerebrovascular and neural cell function. The DKK (Dickkopf-related protein) family of proteins is the most representative group of classical Wnt signaling pathway inhibitors. DKK proteins competitively bind to the Wnt co-receptor LRP5/6, thereby inhibiting the activity of Wnt proteins and exerting their inhibitory effects on the Wnt/β-catenin signaling pathway. We initially found that DKK2 serum levels increased significantly after 4.5 h of recanalization therapy in 20 patients with large vessel occlusive acute stroke, and decreased after 24 h. Increased DKK2 levels were strongly associated with an unfavorable prognosis. This was corroborated in animal models as well, DKK2 expression levels in ischaemic brain tissue and peripheral blood were both significantly elevated and rapidly upregulated within 6-12 h of the onset of cerebral ischemia-reperfusion in mice. In vitro cellular assays showed that DKK2 protein significantly inhibited the activity of the Wnt/β-catenin signaling pathway. We further study showed that upregulation of DKK2 protein levels in the blood of mice by intravenous administration of adenovirus expressing DKK2 protein significantly increased cerebral infarction and neurological impairment in mice with stroke. The increased expression of DKK2 protein in brain tissue is the main reason for the downregulation of Wnt/β-catenin signaling pathway activity after ischemia/reperfusion, which leads to blood-brain barrier damage, neuronal cell death, and neuroinflammation, and ultimately promotes brain tissue damage and neurological dysfunction. It is a new target for drug therapy and has great scientific significance and clinical application prospects.
This clinical study is conducted at Dongguan Hospital of Southern Medical University and Nanfang Hospital of Southern Medical University. Acute ischemic stroke patients with large vessel occlusion who received mechanical thrombectomy therapy and are successfully revascularized will be included and followed up for 90 d, along with testing serum levels of DKK2 protein to explore its correlation with the prognosis of enrolled patients. Venous blood samples will be collected before, and 24 h, 48 h, and 72 h after revascularization treatment in enrolled patients. Venous blood samples will be collected before and 0h, 24 h, 48 h, and 72 h after revascularisation treatment to test serum KKD2 level, and cranial CT examination will be performed before, 24 h, and 72 h after revascularization treatment to detect the occurrence of the transformation of hemorrhage, the severity of cerebral edema, and midline shift after revascularisation treatment. Blood-brain barrier injury-related indicators (MMP-9, ICAM-1) and inflammation-related indicators (IL-6, IL-1β, TNF-α, IL-10) will be measured at each time point of DKK2 testing. NIHSS scores will be evaluated before, 0h (immediately after revascularization treatment), 24 h, 48 h, 72 h, and 7 d after revascularization treatment. The mRS scores will be followed up at 30 days and 90 days after the onset to clarify the relationship between serum DKK2 levels and large vessel occlusion. We aim to investigate the mechanism of DKK2 causing adverse clinical outcomes such as BBB leakage, cerebral edema, and hemorrhagic transformation at a real-world clinical level by collecting blood samples, clinical follow-up, and neurological scoring from stroke patients by measuring DKK2 levels and brain imaging parameters for quantitative assessment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 90 Days
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acute ischemic stroke patients | – | Diagnostic Test: enzyme-linked immunosorbent assay(ELISA)Acute ischemic stroke patients with large vessel occlusion who received mechanical thrombectomy therapy and are successfully revascularized |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Acute ischemic stroke patients with large vessel occlusion who are treated with mechanical embolization and successfully revascularized at Dongguan Hospital of Southern Medical University and Nanfang Hospital of Southern Medical University.
Key inclusion criteria (6 listed)
- Age ≥ 18 years, < 80 years, sex not limited;
- Definite clinical diagnosis of acute ischemic stroke;
- Baseline NIHSS score ≥ 6 and ≤ 25;
- CTA/MRA/DSA examination suggests large vessel occlusion in the anterior circulation (internal carotid artery, M1/M2 segment of the middle cerebral artery);
- The criteria for receiving endovascular treatment in accordance with the Chinese Guidelines for Early Endovascular Intervention in Acute Ischemic Stroke 2018 and have successful revascularization (TICI ≥ grade 2b);
Key exclusion criteria (12 listed)
- Patients with combined posterior circulation infarction;
- The mRS ≥ 2 points before the current episode;
- Patients who are to be treated with or have been treated with anticoagulants;
- Patients with existing or active organ bleeding within 6 months of enrollment, including cerebral hemorrhage, subarachnoid hemorrhage, gastrointestinal tract hemorrhage, fundus hemorrhage, etc;
- The presence of other intracranial pathologies, such as cerebrovascular malformations, cerebral venous lesions, tumors, and other diseases involving the cranium;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| enzyme-linked immunosorbent assay(ELISA)After allowing to stand at room temperature for 2h, blood samples are centrifuged at 4 ℃ for 15 min (12000 rpm) to collect the supernatant. Then, the levels of DKK2, IL-6, IL-1β, TNF-α, and IL-10 in the supernatants are tested by ELISA detection. | Diagnostic test | Acute ischemic stroke patients |
Primary outcome
90-day Functional Outcome.
Time frame: The mRS score will follow up at 90 days.
The favorable prognosis (modified Rankin score [mRS] score ≤ 2) and the unfavorable prognosis group ([mRS] score ≥ 3) within 90 d after onset.
5 secondary outcomes
Incidence of neurological deterioration
Time frame: The NIHSS score will evaluat at the point before revascularization treatment, 0 (immediately after revascularization treatment), 24, 48, 72 hours, and 7 days after revascularization treatment.
Incidence of substantial hemorrhagic transformation
Time frame: At the point before revascularization treatment, 24, and 72 hours after revascularization treatment.
The severity of cerebral edema.
Time frame: At the point before revascularization treatment, 24, and 72 hours after revascularization treatment.
Incidence of midline shift ≥ 6mm.
Time frame: At the point before revascularization treatment, 24, and 72 hours after revascularization treatment.
Levels of major inflammatory indicators in peripheral blood.
Time frame: Before revascularization treatment, 24, 48, 72 hours and 7 days after revascularization treatment.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2024.
- Background: PubMed 30871944GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 May;18(5):439-458. doi: 10.1016/S1474-4422(19)30034-1. Epub 2019 Mar 11.
- Background: PubMed 31248666Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, Li X, Wang L, Wang L, Liu Y, Liu J, Zhang M, Qi J, Yu S, Afshin A, Gakidou E, Glenn S, Krish VS, Miller-Petrie MK, Mountjoy-Venning WC, Mullany EC, Redford SB, Liu H, Naghavi M, Hay SI, Wang L, Murray CJL, Liang X. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2019 Sep 28;394(10204):1145-1158. doi: 10.1016/S0140-6736(19)30427-1. Epub 2019 Jun 24.
- Background: PubMed 32054610Phipps MS, Cronin CA. Management of acute ischemic stroke. BMJ. 2020 Feb 13;368:l6983. doi: 10.1136/bmj.l6983.
- Background: PubMed 31067369Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, Kleinig TJ, Wijeratne T, Curtze S, Dewey HM, Miteff F, Tsai CH, Lee JT, Phan TG, Mahant N, Sun MC, Krause M, Sturm J, Grimley R, Chen CH, Hu CJ, Wong AA, Field D, Sun Y, Barber PA, Sabet A, Jannes J, Jeng JS, Clissold B, Markus R, Lin CH, Lien LM, Bladin CF, Christensen S, Yassi N, Sharma G, Bivard A, Desmond PM, Yan B, Mitchell PJ, Thijs V, Carey L, Meretoja A, Davis SM, Donnan GA; EXTEND Investigators. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Engl J Med. 2019 May 9;380(19):1795-1803. doi: 10.1056/NEJMoa1813046.
- Background: PubMed 29364767Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, Palesch YY, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG; DEFUSE 3 Investigators. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018 Feb 22;378(8):708-718. doi: 10.1056/NEJMoa1713973. Epub 2018 Jan 24.
- Background: PubMed 32299596Patel P, Yavagal D, Khandelwal P. Hyperacute Management of Ischemic Strokes: JACC Focus Seminar. J Am Coll Cardiol. 2020 Apr 21;75(15):1844-1856. doi: 10.1016/j.jacc.2020.03.006.
- Background: PubMed 32374959Yang P, Zhang Y, Zhang L, Zhang Y, Treurniet KM, Chen W, Peng Y, Han H, Wang J, Wang S, Yin C, Liu S, Wang P, Fang Q, Shi H, Yang J, Wen C, Li C, Jiang C, Sun J, Yue X, Lou M, Zhang M, Shu H, Sun D, Liang H, Li T, Guo F, Ke K, Yuan H, Wang G, Yang W, Shi H, Li T, Li Z, Xing P, Zhang P, Zhou Y, Wang H, Xu Y, Huang Q, Wu T, Zhao R, Li Q, Fang Y, Wang L, Lu J, Li Y, Fu J, Zhong X, Wang Y, Wang L, Goyal M, Dippel DWJ, Hong B, Deng B, Roos YBWEM, Majoie CBLM, Liu J; DIRECT-MT Investigators. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. N Engl J Med. 2020 May 21;382(21):1981-1993. doi: 10.1056/NEJMoa2001123. Epub 2020 May 6.
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- Background: PubMed 33070717Shi K, Zou M, Jia DM, Shi S, Yang X, Liu Q, Dong JF, Sheth KN, Wang X, Shi FD. tPA Mobilizes Immune Cells That Exacerbate Hemorrhagic Transformation in Stroke. Circ Res. 2021 Jan 8;128(1):62-75. doi: 10.1161/CIRCRESAHA.120.317596. Epub 2020 Oct 19.
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- Individual participant dataSharing planned: No. The study is proceeding.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhu Shi, PHD study chair
Dongguan Hospital of Southern Medical University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ischemic Stroke, Acute and Ischemia-reperfusion Injury, run by Nanfang Hospital, Southern Medical University at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kaibin Huang, PHD (020-62787664, hkb@smu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
90-day Functional Outcome. (time frame: The mRS score will follow up at 90 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05585255, which also lists 29 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2024.