Clinical trial NCT01558245: Tissue Kallikrein Preventing the Restenosis After Stenting of Symptomatic MCA Atherosclerotic Stenosis
Official title: Tissue Kallikrein Preventing the Restenosis After Stenting of Symptomatic MCA Atherosclerotic Stenosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cerebrovascular Disease
Keywords: ischemic stroke; in-stent restenosis; tissue kallikrein;
the middle cerebral artery; atherosclerotic stenosis
Lead sponsor: Jinling Hospital, China
Sponsor class: OTHER
First posted: 2012-03-20
Enrollment: 99
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Eligibility 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

Primary outcomes:
measure: Target lesion failure
timeFrame: 12 months
Secondary outcomes:
measure: Clinical endpoint
timeFrame: 12 months
Other outcomes:
measure: Laboratory data
timeFrame: 12 months
Locations:
city: Nanjing
country: China
facility: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine
state: Jiangsu
Study officials:
affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine
name: Renliang Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shi R, Zhang R, Yang F, Lin M, Li M, Liu L, Yin Q, Lin H, Xiong Y, Liu W, Fan X, Dai Q, Zhou L, Lan W, Cao Q, Chen X, Xu G, Liu X. Tissue Kallikrein Prevents Restenosis After Stenting of Severe Atherosclerotic Stenosis of the Middle Cerebral Artery: A Randomized Controlled Trial. Medicine (Baltimore). 2016 Feb;95(6):e2809. doi: 10.1097/MD.0000000000002809.
citation: Lan W, Yang F, Liu L, Yin Q, Li M, Li Z, Sang H, Xu G, Ma M, Zhang Z, Liu Z, Liu X, Zhang R. Tissue kallikrein preventing the restenosis after stenting of symptomatic MCA atherosclerotic stenosis (KPRASS). Int J Stroke. 2014 Jun;9(4):533-5. doi: 10.1111/ijs.12229. Epub 2013 Dec 20.