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

Cerebrovascular Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01558245
• Other study ID #: KPRASS
• Status: Recruiting
• Phase: Phase 2
• First received: December 14, 2011
• Last updated: September 11, 2013
• Start date: December 2011
• Est. completion date: December 2013

Study information

• Verified date: September 2013
• Source: Jinling Hospital, China
• Contact: Renliang Zhang, MD
• Phone: + 86-25-8480386
• Email: zhangrenliang[@]gmail.com
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 99
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cerebrovascular Disease
• Cerebrovascular Disorders

Intervention

Drug:
• tissue kallikrein
Human urinary kallidinogenase can transform kininogen to bradykinin (kinin) and vasodilatory factors (kallidin)

Locations

Country	Name	City	State
China	Department of Neurology, Jinling Hospital, Nanjing University School of Medicine	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Jinling Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Laboratory data	Laboratory data including bradykinin (BK), TK, platelet inhibitory rate, cGMP, cAMP, hs-CRP, TNF-a, IL-6, LDL-Ch and HDL-Ch will be recorded	12 months	Yes
Primary	Target lesion failure	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.	12 months	Yes
Secondary	Clinical endpoint	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.	12 months	Yes