Human Urinary Kallidinogenase Improve Short Term Motor Functional Outcome of Acute Ischemia Stroke Patients

NCT04102956 | Completed Phase 4 Results

• 1 other identifier: 2018-P023
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stroke, Acute

Outcome Measures

Primary Outcomes (7)

• 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

  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

Study Arms (2)

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.

Drug: Kallikrein

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.

Interventions

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.

Also known as: Human urinary kallidinogenase

Kallikrein+Standard treatment group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• The Second Hospital of Hebei Medical University: lead

Study Sites (1)

Second hospital of hebei medical university

Shijiazhuang, Hebei, 050000, China

Location

Related Publications (1)

• 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.

  PMID: 38526971 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Kallikreins

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Results Point of Contact

• Title: Xiaoyun Liu PhD
• Organization: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

audrey-l@163.com

+8613191887318

Study Officials

• Xiaoyun Liu, Prf.

  The Second Hospital of Hebei Medical University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director of Neurology Department

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: September 25, 2019
• Study Start: July 1, 2017
• Primary Completion: March 1, 2019
• Study Completion: August 25, 2019
• Last Updated: March 1, 2021
• Results First Posted: March 1, 2021

Record last verified: 2021-02

Locations

CN (1)