Multi-"Omics" Research of Danhong Injection to Treat Acute Ischemic Stroke

The purpose of this study is to explore the pharmacological mechanism of Danhong injection in the treatment of acute ischemic stroke.

Study Overview

• Status: Completed
• Conditions: Acute Stroke
• Intervention / Treatment: Procedure: Standard medical care; Drug: Danhong injection; Drug: placebo

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Henan
    • Nanyang, Henan, China, 473065
      • Nanshi Hospital of Nanyang
  • Liaoning
    • Panjin, Liaoning, China, 124013
      • Panjin Central Hospital
    • Shenyang, Liaoning, China
      • 202 Military Hospital of China
  • Neimenggu
    • Chifeng, Neimenggu, China, 024005
      • Affiliated Hospital of Chifeng University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Female or male inpatients

   • Age: 18 - 70 years.
   • Clinical diagnosis of ischemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition and/or gaze, vision or neglect. Ischemic stroke is defined as an event characterized by the sudden onset of an acute focal neurologic deficit presumed to be due to cerebral ischemia after CT scan excludes hemorrhage.
   • Clinical diagnosis of "Xueyu Zheng" (Blood Stasis Syndrome) as the scores of Chinese medicine symptoms scales of "Xueyu Zheng" in ischemic stroke ≥ 20. The Chinese medicine symptoms scales of "Xueyu Zheng" is defined as following (1)hemiplegia-10,(2)numbness of limbs-10，(3) dark face-9,(4)purple or dark lip-8,(5)Roughness of skin-4, (6) pain with fixed point-5, (7) purple or dark tongue-10,(8)ecchymosis on tongue-10,(9)purple sublingual vessel-10,(10)varicose sublingual vessel-8,(11)unsmooth pulse-8,(12)intermittent pulse-1.
   • Onset of symptoms in 1 week prior to initiation of administration of study drug.
   • Clinical diagnosis of cerebral anterior circulation obstruction.
   • 4≤NIHSS<20.
   • Patient is willing to participate voluntarily and to sign a written patient informed consent. Informed consent will be obtained from each patient or the subject's legally authorized representative or relatives, or deferred where applicable, according to the regulatory and legal requirements of the participating centers.

2. Female or male healthy volunteer

   • Age: 18 - 70 years.
   • Medical history, physical examination, vital signs, electrocardiogram(ECG) and laboratory results (including renal function, hepatic function, et al)with no clinically significant findings.
   • Healthy volunteer is willing to participate voluntarily and to sign a written informed consent form. Informed consent will be obtained from each volunteer, according to the regulatory and legal requirements of the participating centers.

Exclusion Criteria:

1. Female or male inpatients

   • Evidence of intracranial hemorrhage (ICH) or other cerebral diseases (eg.vascular malformation, tumor, abscess or multiple sclerosis etc.)on the CT-or MRI-scan.
   • Patients with thrombolysis or endovascular treatment.
   • Known history of allergy or suspected allergic to the drug.
   • Blood glucose 2.8 or > 16.8 mmol / l under the treatment of diabetes or with severe complications due to diabetes (eg. peripheral neuropathy, diabetic gangrene).
   • Liver function impairment with the value of ALT or AST over 1.5-fold of normal value.
   • Renal dysfunction with the value of serum creatinine over 1.5-fold of normal value.
   • Severe cardiac dysfunction on echocardiogram or the grade of heart function over Ⅲ grade.
   • History of prior stroke with mRS ≥2.
   • Complicated with atrial fibrillation.
   • Severe stroke as assessed by appropriate imaging techniques (eg. massive cerebral infarction including more than one lobe of brain or over 1/3 of blood-supply area of middle cerebral artery).
   • Prior disable patients.
   • Hemorrhagic tendency or recent severe or dangerous bleeding in 3 months.
   • Suspected addicted into alcohol or drug abuse.
   • With severe complications that would make the condition more complicated assessed by the investigator.
   • Woman with pregnancy, lactation or positive result of pregnancy test, or women who want to be pregnant in recent 6 months.
   • Woman who is under menstrual period.
   • Patient who is participating in other trials or has been participated in other trials in recent 3 months.

2. Healthy volunteer

   • Had a known history of chronic diseases including stroke, heart diseases, diabetes, COPD, Neuropsychiatric diseases and chronic infectious diseases, etc.
   • Coagulation disorders.
   • Conditions with increased bleeding risk.
   • Trauma or surgery in the 6 months prior to the study.
   • Use of any medication 4 weeks prior to the trial.
   • History of drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Danhong injection; Based on the standard medical care, 40ml of Danhong injection, added into 250ml of 0.9% saline, given by continuous IV infusion at 2.5ml/min within 2 hours.	Procedure: Standard medical care; Standard medical care is in accordance with China Guideline for the diagnosis and treatment of acute ischemic stroke (2010), including medical care for vital signs, control of temperature, blood pressure and glucose, improving cerebral blood circulation, antiplatelet treatment and nutritional supportive care.; Drug: Danhong injection; 40ml Danhong injection added into 250ml 0.9% saline by an independent research nurse, sealed with brown bag in order to make the investigators and patients blinded, using brown infusion tube for infusion; Other Names: A kind of injection made from two kind of Chinese herbs: Salvia miltiorrhiza and Safflower.
Placebo Comparator: placebo; Based on the standard medical care, 40ml of 0.9% saline as the placebo, added into 250ml of 0.9% saline, given by continuous IV infusion at 2.5ml/min within 2 hours.	Procedure: Standard medical care; Standard medical care is in accordance with China Guideline for the diagnosis and treatment of acute ischemic stroke (2010), including medical care for vital signs, control of temperature, blood pressure and glucose, improving cerebral blood circulation, antiplatelet treatment and nutritional supportive care.; Drug: placebo; 0.9% saline added into 250ml 0.9% saline by an independent research nurse, sealed with brown bag in order to make the investigators and patients blinded, using brown infusion tube for infusion
No Intervention: healthy volunteer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Modified Rankin Scale 0-1 (favourable outcome) at Day 90	Day 90

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes of serum proteomics in 36 patients selected from certain center	We wish to identify protein biomarkers in the blood that changed with Danhong treatment	Day 0, Day 14, Day 90
The microRNA profile in 10 healthy volunteer		Day0
The mRNA profiles in 10 healthy volunteer		Day0
The proteomics profiles of 10 healthy volunteer		Day 0

Collaborators and Investigators

• Sponsor: China Academy of Chinese Medical Sciences
• Collaborators: China Food and Drug Administration
• Investigators: Principal Investigator: Wang Zhong, Professor, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences; Principal Investigator: Zhao Xingquan, Professor, Beijing Tiantan Hospital; Study Chair: Wang Yongyan, Professor, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences; Principal Investigator: Jiang Zhilin, Professor, 202 Military Hospital of China

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): July 1, 2020

Study Registration Dates

• First Submitted: June 20, 2014
• First Submitted That Met QC Criteria: June 25, 2014
• First Posted (Estimate): June 27, 2014

Study Record Updates

• Last Update Posted (Actual): July 15, 2020
• Last Update Submitted That Met QC Criteria: July 14, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Traditional Chinese Medicine; Proteomics; Acute Ischemic Stroke
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: DH20140604