Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Acute cerebral infarction is a common type of ischemic stroke, causing brain dysfunction in patients with high morbidity and disability. With the changes in people's diet, lifestyle patterns and population aging, the incidence of acute cerebral infarction has increased year by year, which has become an important cause of disability and death in middle-aged and elderly patients. The human urinary kallidinogenase (HUK) was used in China in the management of acute ischemic stroke (AIS) in recent years. However, the mechanism of HUK on AIS has not been systematically investigated. This study aimed to assess the effect of HUK on motor functional outcome and relative corticospinal tract recovery in the patients with AIS. Diffusion tensor imaging(DTI) and diffusion tensor tractography(DTT) have all been used to observe features of cerebral white matter fibrous structures. In addition, diffusion tensor tractography which is used to trace fiber bundle and evaluate white matter fiber bundle integrity and direction is the only non-invasive imaging method to display the corticospinal tract in vivo.
A total of 80 AIS patients with the unilateral corticospinal tract damage who were matched for inclusion criterion were enrolled in this randomized controlled trial. The HUK group was administered with HUK and standard treatment(general treatment for anti-platelet, lipid-lowering and improving circulation,etc.), the control group received only standard treatment. Kallikrein+Standard Treatment Group (general Treatment for anti-platelet, lipid-lowering and improving circulation,etc.) and Standard Treatment Group were randomly selected.
At admission and discharge, National Institute of Health Stroke Scale(NIHSS), Barthel Index(BI), muscle strength were scored; The DTI were performed and DTT were utilized to reconstruct corticospinal tract to observe its direction and appearance changes then to evaluate the integrity and impairment degree of the corticospinal tract which was divided into four grades according to DTT presented compression, deformation, or rupture. Fractional anisotropy(FA) and apparent diffusion coefficient(ADC) of infarct region and corresponding contralateral normal regions were measured.
Blood samples were collected to test serum myelin basic protein(MBP) and vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay (ELISA). The primary endpoint is the short-term motor function prognosis of the AIS patients, we also evaluated the recovery of corticospinal tract and the serum MBP and VEGF changes during treatment in two groups.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Kallikrein+Standard treatment group | Experimental | The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days. |
|
| Standard treatment group | No Intervention | The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Kallikrein | Drug | HUK has been approved by China's State Food and Drug Administration as a state category I new drug for the treatment of stroke patients. Based on the available evidence, HUK injection ameliorates neurological deficits and improves long-term outcomes. |
| Measure | Description | Time Frame |
|---|---|---|
| Myelin Basic Protein (MBP) Comparison Between the Two Groups Before and After Treatment | The effect of Kallikrein on myelin basic protein (MBP) was determined by comparing the changes of MBP before and after treatment between the Kallikrein+Standard treatment group and the standard treatment group. | before (baseline) and after treatment (14 ± 5 days) |
| Comparison of Vascular Endothelial Growth Factor (VEGF) Before and After Treatment Between the Kallikrein+Standard Treatment Group and Standard Treatment Group | The effect of Kallikrein on vascular endothelial growth factor (VEGF) was judged by comparing the changes of VEGF before and after treatment in the Kallikrein+Standard treatment group and the standard treatment group. | before (baseline) and after treatment (14 ± 5 days) |
| Changes of Barthel Index(BI) Before and After Treatment in the Two Groups | The Barthel Index(BI) is 0 to 100 points. The higher the score, the better the patient's motor function and behavior. The effect of Kallikrein on Barthel Index was judged by comparing the changes of Barthel Index before and after treatment in the Kallikrein+Standard treatment group and the standard treatment group. | before (baseline) and after treatment (14 ± 5 days) |
| Changes in Muscle Strength of the Kallikrein+Standard Treatment Group and the Standard Treatment Group Before and After Treatment | Using the recording method of grade 6 muscle strength of 0-5 grade, grade 0 means no muscle contraction, grade 5 means normal muscle strength. The effect of Kallikrein on muscle strength was judged by comparing the changes of muscle strength before and after treatment in the Kallikrein+Standard treatment group and the standard treatment group. | before (baseline) and after treatment (14 ± 5 days) |
| Changes of National Institute of Health Stroke Scale(NIHSS) Before and After Treatment in the Two Groups |
Not provided
Not provided
Inclusion Criteria:
18 years old ≤ age <80 years old; Within 72 hours of onset; Diagnosed as acute cerebral infarction, and confirmed by magnetic resonance imaging as an acute infarct in the unilateral corticospinal tract; The patient's onset muscle strength grade <4; No history of cerebral infarction or residual physical activity disorder; No other intracranial lesions; Patients or their legal representatives voluntarily Sign the informed consent form;
Exclusion Criteria:
Intracranial hemorrhagic disease: cerebral hemorrhage, subarachnoid hemorrhage, etc.; Transient ischemic attack; Intravenous thrombolysis and interventional thrombectomy; Serious physical illness affects limb movement before enrollment ; Apply other drugs with nutritional nerves and regeneration during the study period; Unstable vital signs, severe liver and kidney diseases or malignant tumors; Incomprehensible or incapable of obeying the research procedure or being unable to follow up due to mental illness, cognitive or emotional disorders;
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Xiaoyun Liu, Prf. | The Second Hospital of Hebei Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Second hospital of hebei medical university | Shijiazhuang | Hebei | 050000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38526971 | Derived | Li P, Lu H, Shi X, Yan J, Zhou L, Yang J, Wang B, Zhao Y, Liu L, Zhu Y, Xu L, Yang X, Su X, Yang Y, Zhang T, Guo L, Liu X. Protective effects of human urinary kallidinogenase against corticospinal tract damage in acute ischemic stroke patients. Neuroreport. 2024 May 8;35(7):431-438. doi: 10.1097/WNR.0000000000002028. Epub 2024 Mar 12. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Kallikrein+Standard Treatment Group | The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days. |
| FG001 | Standard Treatment Group | The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Kallikrein+Standard Treatment Group | The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days. |
| BG001 | Standard Treatment Group |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Myelin Basic Protein (MBP) Comparison Between the Two Groups Before and After Treatment | The effect of Kallikrein on myelin basic protein (MBP) was determined by comparing the changes of MBP before and after treatment between the Kallikrein+Standard treatment group and the standard treatment group. | Among the enrolled 80 subjects, 59 taken the blood samples (33 in the Kallikrein+Standard treatment group and 26 in the Standard treatment group) to test serum myelin basic protein(MBP) and vascular endothelial growth factor (VEGF). | Posted | Median | Inter-Quartile Range | pg/ml | before (baseline) and after treatment (14 ± 5 days) |
|
During the hospitalization of all participants within 14 ± 5 days
No adverse events
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Kallikrein+Standard Treatment Group | The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days. |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Xiaoyun Liu PhD | Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China. | +8613191887318 | audrey-l@163.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Jul 15, 2019 | Dec 16, 2020 | ICF_001.pdf |
| Prot | Yes | No | No | Study Protocol | Jul 15, 2019 | Dec 18, 2020 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 15, 2019 | Dec 18, 2020 | SAP_003.pdf |
Not provided
| ID | Term |
|---|---|
| D020521 | Stroke |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D007610 | Kallikreins |
| ID | Term |
|---|---|
| D012697 | Serine Endopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
| D006867 | Hydrolases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
The NIHSS score is 0 to 42 points. The higher the score, the more severe the nerve damage. The change of NIHSS score is calculated as the value at the earlier time point minus the value at the later time point, that is, the value at the time of admission minus the value after the end of treatment, and then the comparison between groups is performed to obtain the current result. |
| before (baseline) and after treatment (14 ± 5 days) |
| Change of Fractional Anisotropy Valuev Decline Rate† (FA Decline Rate†) | The FA value is used to express the anisotropy, which indicates the anisotropic component of water molecules accounts for the total value of diffusion tensor,and ranges from 0 to 1, the closer the value is to 1, the better the fiber bundle integrity. †FA decline rate = (FA contralateral- FA ipsilateral) / FA contralateral， Used to compare the FA decline rate† of the two groups after treatment. A more substantial decrease of FA values is believed to represent the most severely ischemic tissue. | After 14 ± 5 days of treatment |
| Change of Apparent Diffusion Coefficient Value Decline Rate‡（ADC Decline Rate‡） | The ADC value of normal brain tissue is in the range of 0.7-0.9×10﹣³m㎡/s. When the brain tissue is acutely affected, it is mostly decreased, and it is mostly increased in subacute or chronic disease. The upper and lower limits of abnormal changes in ADC value are 0.4-2.5×10﹣³m㎡/s. ‡ ADC decline rate = (ADCcontralateral- ADCipsilateral) / ADCcontralateral；Used to compare the ADC decline rate‡ of the two groups after treatment. A more substantial decrease of ADC values is believed to represent the most severely ischemic tissue. | After 14 ± 5 days of treatment |
The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Hypertension (number, %) | Count of Participants | Participants | No |
|
| Diabetes (number, %) | Count of Participants | Participants | No |
|
| Coronary heart disease (number, %) | Count of Participants | Participants | No |
|
| Hyperhomocysteinemia (number, %) | Count of Participants | Participants | No |
|
| Previous history of cerebral infarction (number, %) | Count of Participants | Participants | No |
|
| Smoking and drink (number, %) | Count of Participants | Participants | No |
|
| Muscle strength at admission，Median (IQR) | The 6-level muscle strength recording method of 0-5 levels is used. Level 0 means no muscle contraction, and level 5 means normal muscle strength. | Median | Inter-Quartile Range | units on a scale |
|
| NIHSS score at admission ( Mean±SD) | The National Institute of Health Stroke Scale(NIHSS) ranges from 0 to 42, with the higher the score, the more severe the nerve damage. | Mean | Standard Deviation | units on a scale |
|
| BI index at admission，Median (IQR) | Barthel Index(BI) ranges from 0 to 100 points, the higher the score, the stronger the self-care ability. | Median | Inter-Quartile Range | units on a scale |
|
| FA value at admission ( Mean±SD) | The Fractional Anisotropy (FA) value is used to express the anisotropy, which indicates the anisotropic component of water molecules accounts for the total value of diffusion tensor,and ranges from 0 to 1, the closer the value is to 1, the better the fiber bundle integrity. | 78 taken the DTI imaging at admission (40 in the Kallikrein+Standard treatment group and 38 in the Standard treatment group) | Mean | Standard Deviation | units on a scale |
|
| ADC value at admission ( Mean±SD) | The ADC value of normal brain tissue is in the range of 0.7-0.9×10﹣³m㎡/s. When the brain tissue is acutely affected, it is mostly decreased, and it is mostly increased in subacute or chronic disease. The upper and lower limits of abnormal changes in ADC value are 0.4-2.5×10﹣³m㎡/s. | Measure Analysis Population Description: 78 taken the DTI imaging at admission (40 in the Kallikrein+Standard treatment group and 38 in the Standard treatment group). | Mean | Standard Deviation | m㎡/s |
|
| The grade of the severity of corticospinal tract injury ( number, %) | The severity of the corticospinal tract injury evaluated according to DTT presented compression, deformation, or rupture was classified as: Grade 1 refers to complete corticospinal tract; Grade 2 refers to slight corticospinal injury less than 50%. Grade 3 refers to moderate corticospinal tract injury between 50%~75%; Grade 4 refers to severe corticospinal tract injury, almost interrupted more than 75%. | Count of Participants | Participants | No |
|
| Intracranial arterial stenosis ( number, %) | Count of Participants | Participants | No |
|
| VEGF Median (IQR) (pg/ml) | Among the enrolled 80 subjects, 59 taken the blood samples (33 in the Kallikrein+Standard treatment group and 26 in the Standard treatment group) to teste the concentrations of VEGF and MBP. | Median | Inter-Quartile Range | pg/ml |
|
| MBP Median (IQR) (pg/ml) | Among the enrolled 80 subjects, 59 taken the blood samples (33 in the Kallikrein+Standard treatment group and 26 in the Standard treatment group) to teste the concentrations of VEGF and MBP. | Median | Inter-Quartile Range | pg/ml |
|
| OG001 | Standard Treatment Group | The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days. |
|
|
| Primary | Comparison of Vascular Endothelial Growth Factor (VEGF) Before and After Treatment Between the Kallikrein+Standard Treatment Group and Standard Treatment Group | The effect of Kallikrein on vascular endothelial growth factor (VEGF) was judged by comparing the changes of VEGF before and after treatment in the Kallikrein+Standard treatment group and the standard treatment group. | Among the enrolled 80 subjects, 59 taken the blood samples (33 in the Kallikrein+Standard treatment group and 26 in the Standard treatment group) to test serum myelin basic protein(MBP) and vascular endothelial growth factor (VEGF). | Posted | Median | Inter-Quartile Range | ng/ml | before (baseline) and after treatment (14 ± 5 days) |
|
|
|
| Primary | Changes of Barthel Index(BI) Before and After Treatment in the Two Groups | The Barthel Index(BI) is 0 to 100 points. The higher the score, the better the patient's motor function and behavior. The effect of Kallikrein on Barthel Index was judged by comparing the changes of Barthel Index before and after treatment in the Kallikrein+Standard treatment group and the standard treatment group. | Posted | Median | Inter-Quartile Range | score on a scale | before (baseline) and after treatment (14 ± 5 days) |
|
|
|
| Primary | Changes in Muscle Strength of the Kallikrein+Standard Treatment Group and the Standard Treatment Group Before and After Treatment | Using the recording method of grade 6 muscle strength of 0-5 grade, grade 0 means no muscle contraction, grade 5 means normal muscle strength. The effect of Kallikrein on muscle strength was judged by comparing the changes of muscle strength before and after treatment in the Kallikrein+Standard treatment group and the standard treatment group. | Posted | Mean | Inter-Quartile Range | score on a scale | before (baseline) and after treatment (14 ± 5 days) |
|
|
|
| Primary | Changes of National Institute of Health Stroke Scale(NIHSS) Before and After Treatment in the Two Groups | The NIHSS score is 0 to 42 points. The higher the score, the more severe the nerve damage. The change of NIHSS score is calculated as the value at the earlier time point minus the value at the later time point, that is, the value at the time of admission minus the value after the end of treatment, and then the comparison between groups is performed to obtain the current result. | Posted | Mean | Standard Deviation | score on a scale | before (baseline) and after treatment (14 ± 5 days) |
|
|
|
| Primary | Change of Fractional Anisotropy Valuev Decline Rate† (FA Decline Rate†) | The FA value is used to express the anisotropy, which indicates the anisotropic component of water molecules accounts for the total value of diffusion tensor,and ranges from 0 to 1, the closer the value is to 1, the better the fiber bundle integrity. †FA decline rate = (FA contralateral- FA ipsilateral) / FA contralateral， Used to compare the FA decline rate† of the two groups after treatment. A more substantial decrease of FA values is believed to represent the most severely ischemic tissue. | Posted | Median | Inter-Quartile Range | percentage of decline rate | After 14 ± 5 days of treatment |
|
|
|
| Primary | Change of Apparent Diffusion Coefficient Value Decline Rate‡（ADC Decline Rate‡） | The ADC value of normal brain tissue is in the range of 0.7-0.9×10﹣³m㎡/s. When the brain tissue is acutely affected, it is mostly decreased, and it is mostly increased in subacute or chronic disease. The upper and lower limits of abnormal changes in ADC value are 0.4-2.5×10﹣³m㎡/s. ‡ ADC decline rate = (ADCcontralateral- ADCipsilateral) / ADCcontralateral；Used to compare the ADC decline rate‡ of the two groups after treatment. A more substantial decrease of ADC values is believed to represent the most severely ischemic tissue. | Posted | Median | Inter-Quartile Range | percentage of decline rate | After 14 ± 5 days of treatment |
|
|
|
| 0 |
| 42 |
| 0 |
| 42 |
| 0 |
| 42 |
| EG001 | Standard Treatment Group | The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days. | 0 | 38 | 0 | 38 | 0 | 38 |
Not provided
Not provided
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D004798 |
| Enzymes |
| D045762 | Enzymes and Coenzymes |
| D057057 | Serine Proteases |
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001685 | Biological Factors |
| Grade 3 |
|
| Grade 4 |
|