Tissue Kallikrein Preventing the Restenosis After Stenting of Symptomatic MCA Atherosclerotic Stenosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Jinling Hospital, China
Sponsor:
Information provided by (Responsible Party):
Zhang Renliang, Jinling Hospital, China
ClinicalTrials.gov Identifier:
NCT01558245
First received: December 14, 2011
Last updated: September 11, 2013
Last verified: September 2013
  Purpose

The study aims to determine whether tissue kallikrein (TK) is efficacy for preventing the long-term in-stent restenosis (ISR) after stenting of symptomatic atherosclerotic stenosis of the middle cerebral artery (MCA) M1 segment


Condition Intervention Phase
Cerebrovascular Disease
Drug: tissue kallikrein
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Prevention
Official Title: Tissue Kallikrein Preventing the Restenosis After Stenting of Symptomatic MCA Atherosclerotic Stenosis

Further study details as provided by Jinling Hospital, China:

Primary Outcome Measures:
  • Target lesion failure [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Patients will be evaluated at 1 month, 6 months, and 12 months after the stenting. The primary outcomes are the asymptomatic or symptomatic in-stent restenosis ≥ 50% (affirmed by digital subtraction angiography at 6 and 12 months), new stroke (ischemic and hemorrhagic) or aggravation of the previous ischemic stroke ipsilateral to the severe stenotic artery.


Secondary Outcome Measures:
  • Clinical endpoint [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Stroke of other artery territories, myocardial infarction and vascular death will be conducted in-hospital and planned at 1 month, 6 months, and 12 months.


Other Outcome Measures:
  • Laboratory data [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Laboratory data including bradykinin (BK), TK, platelet inhibitory rate, cGMP, cAMP, hs-CRP, TNF-α, IL-6, LDL-Ch and HDL-Ch will be recorded


Estimated Enrollment: 99
Study Start Date: December 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tissue kallikrein group
Patients in this group will be prescribed with intravenous infusion of TK (0.15 PNAU/d, dissolved in 100ml saline) for 7 days after stenting and then oral administration of pancreatic kallikrein enteric-coated tablet (240U, 3/d) to the end of study. As the foundation treatment, all the enrolled patients will receive aspirin (100 mg/d), clopidogrel (75 mg/d), and atorvastatin (20 mg/d) for the first 6 months and continue with the combination of aspirin and atorvastatin at the previous dosage.
Drug: tissue kallikrein
Human urinary kallidinogenase can transform kininogen to bradykinin (kinin) and vasodilatory factors (kallidin)
Other Name: Human urinary kallidinogenase (HUK)
No Intervention: Control group
Patients in control group will receive foundation treatment, including aspirin (100 mg/d), clopidogrel (75 mg/d), and atorvastatin (20 mg/d) for the first 6 months and continue with the combination of aspirin and atorvastatin at the previous dosage.

Detailed Description:

A series of studies have confirmed the kallikrein-kinin system (KKS), including kallikrein, kininogen and kinin, plays an important role in the regulation of inflammation secondary to acute and chronic ischemic brain injury. Some researchers found that hTK gene delivery can inhibit the formation of neointimal induced by the common carotid artery ligation in mice. Further study revealed hTK gene transfection in VSMC lead to increased secretion of TK and inhibition of VSMC proliferation. In addition, it was also observed that the serum TK levels were coincident with the carotid artery stenosis. The more severe the stenosis is, the higher the serum TK level is, and the serum TK decreased after carotid artery angioplasty and stent placement. These results suggest that KKS play an important regulatory role in vascular remodeling and TK may exert a beneficial influence in the process of ISR

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. TIA or stroke in the MCA territory refractory to aggressive anti-platelet and regular statin therapy in 3 months
  2. Symptomatic MCA M1 segment stenosis ≥ 70% confirmed with DSA
  3. Successfully treated with PTAS without acute surgical complications in 12 hours after operation
  4. All patients provided fully informed consent

Exclusion Criteria:

  1. Using angiotensin-converting enzyme inhibitors
  2. Severe cardiopulmonary dysfunction, chronic liver disease (A / G inversion, ALT increased 2-fold greater than normal), abnormal renal function (serum creatinine greater than 1.5 times normal)
  3. Allergies, the history of allergy to multi-drug
  4. The history of cerebral hemorrhage, brain tumors, brain trauma, cerebral embolism and other brain lesions
  5. During pregnancy or breast-feeding
  6. Not expected to complete follow-up
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01558245

Contacts
Contact: Renliang Zhang, MD + 86-25-8480386 zhangrenliang@gmail.com

Locations
China, Jiangsu
Department of Neurology, Jinling Hospital, Nanjing University School of Medicine Recruiting
Nanjing, Jiangsu, China
Contact: Renliang Zhang, MD    + 86-25-8480386    zhangrenliang@gmail.com   
Sponsors and Collaborators
Jinling Hospital, China
Investigators
Principal Investigator: Renliang Zhang, MD Department of Neurology, Jinling Hospital, Nanjing University School of Medicine
  More Information

No publications provided by Jinling Hospital, China

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Zhang Renliang, Clinical Professor and Associate Director of Department of Neurology, Jinling Hospital, China
ClinicalTrials.gov Identifier: NCT01558245     History of Changes
Other Study ID Numbers: KPRASS
Study First Received: December 14, 2011
Last Updated: September 11, 2013
Health Authority: China: Ministry of Health

Keywords provided by Jinling Hospital, China:
ischemic stroke; in-stent restenosis; tissue kallikrein;
the middle cerebral artery; atherosclerotic stenosis

Additional relevant MeSH terms:
Cerebrovascular Disorders
Constriction, Pathologic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Kallikreins
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fertility Agents, Male
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2014