Cerebrovascular Disease
Conditions
Keywords
ischemic stroke; in-stent restenosis; tissue kallikrein;, the middle cerebral artery; atherosclerotic stenosis
Brief summary
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
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
Interventions
DRUGtissue kallikrein
Human urinary kallidinogenase can transform kininogen to bradykinin (kinin) and vasodilatory factors (kallidin)
Sponsors
Jinling Hospital, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Target lesion failure | 12 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Clinical endpoint | 12 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Laboratory data | 12 months | 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 |
Countries
China
Contacts
Primary ContactRenliang Zhang, MD
Outcome results
None listed