Clinical trial NCT02594800: Intensive Rosuvastatin Therapy on Cerebral Hemodynamics in Patients With Atherosclerotic Intracranial Arterial Stenosis
Official title: The Impact of Intensive Rosuvastatin Therapy on Cerebral Hemodynamics in Patients With Atherosclerotic Intracranial Arterial Stenosis Evaluated by Computed Tomography Perfusion (CTP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atherosclerosis
Keywords: Atherosclerotic Intracranial Arterial Stenosis
Intensive Rosuvastatin Therapy
Computed Tomography Perfusion (CTP)
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2015-11-03
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Atherosclerotic intracranial arterial stenosis (AICAS) corresponds to luminal narrowing of the major intracranial arteries. The prevalence of intracranial atherosclerotic stenosis accounts for 33% to 67% of stroke or transient ischemic attack (TIA) cases in China and other countries in Asia. AICAS is also highly associated with the risk of stroke recurrence. Possible mechanisms of cerebral infarction secondary to AICAS are likely linked with hemodynamic compromise distal to site of stenosis.

Computed tomography perfusion (CTP) can be used to evaluate vasoreactivity and cerebrovascular reserve in patients with AICAS and predict future stroke. The parameters of CTP include ①cerebral blood flow(CBF),② cerebral blood volume(CBV) and ③mean transit time(MTT). Relative regional cerebral blood flow (rCBF) was evaluated as the percentage radioisotope counts in the region of interest (ROI) of the affected side against the corresponding ROI in the unaffected contralateral side.

Statins can decrease the incidence of transient ischemic attack or ischemic stroke and improve stroke outcome. Few studies focus on the relationship between statins therapy and cerebral perfusion.

Whether intensive rosuvastatin therapy compared with standard rosuvastatin therapy can improve hemodynamic situation and cerebral perfusion status in AICAS has not been illustrated.

Based on those studies, the investigators hypothesized that intensive rosuvastatin may also improve the symptoms of AICAS not only through enhancing the stability of atherosclerotic plaques, but also its pleiotropic effects. So it can change the hemodynamic status around the plaque and increase cerebral flow in the downstream territory. So in this study the investigators try to analysis statin's impact on the hemodynamic changes as well as the downstream perfusion which is determined by CTP.

Detailed description: This is an prospective, randomized, single-blind, single center clinical trial to evaluate the effect of intensive rosuvastatin therapy compared with standard rosuvastatin therapy on improve the cerebral perfusion in Chinese patients with atherosclerotic intracranial arterial stenosis between 50-99%.

The study will enroll 44 patients and randomly divided into 2 groups: standard dose rosuvastatin therapy (SRT 10mg/day)and intensive dose rosuvastatin therapy (IRT 20mg/day)in a 1:1 ratio. Both groups will be prescribed with statin based on other routine medication for stroke for 52 weeks. CTP will be performed at baseline and 52 weeks after treatment. Lipid levels and biochemical examinations will be obtained at baseline and 13, 26, 39, 52 week. AEs(Adverse Events)/SAEs(Serious Adverse Events) will be collected and recorded in CRF(Case Report Form) from the signing of informed consent throughout the study until and including the last visit.

Study Endpoints: Primary endpoint: Compared with standard dose rosuvastatin therapy 10mg/day, the change of relative cerebral blood flow (CBF) by CTP after intensive dose rosuvastatin therapy 20mg/day treatment for 52 weeks.Secondary endpoints: (1) Compared with standard dose rosuvastatin therapy 10mg/day, the changes of relative cerebral blood volume (CBV) by CTP after rosuvastatin 20mg/d treatment for 52 weeks (2) Compared with standard dose rosuvastatin therapy 10mg/day, the changes of relative mean transit time (MTT) by CTP after rosuvastatin 20mg/d treatment for 52 weeks (3) Compared with standard dose rosuvastatin therapy 10mg/day, the changes of lipid parameters (LDL-C, HDL-C, TG(Triglyceride), TC(Total Cholesterol), Apo A and Apo B ) after rosuvastatin 20mg/d for 52 weeks (4) Safety.

Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent
2. Male and female adults aged 18-80years old
3. Recent (within 3 months) ischemic stroke or TIA;
4. Intracranial large artery (intracranial internal artery, middle cerebral artery M1, vertebral artery and basilar artery) stenosis between 50-99%.
5. Statin naïve:defined as receiving no statin therapy within 3 months

Exclusion Criteria:

1. Cardioembolic stroke;
2. Rosuvastatin use is contraindicated;
3. Allergic to contrast agents;
4. Chronic devastating illness, multiple organ failure;
5. Dementia or mental disorder unable to return for repeat brain CTP.
6. Administration of lipid-lowering drugs (statin, clofibrate, probucol or analog, nicotinic acid, or other prohibited drug) before enrollment.
7. Active liver disease or aminopherase ≧3 ULN(Upper Limit of Normal)
8. Renal function damage. GFR（Glomerular Filtration Rate） ﹤30ml/min

Primary outcomes:
measure: the change of relative cerebral blood flow (CBF) （ml/100g/min）by CTP
timeFrame: 52 weeks
Secondary outcomes:
measure: the changes of relative cerebral blood volume (CBV)（ml/100g） by CTP
timeFrame: 52 weeks
measure: the changes of relative mean transit time (MTT)（min） by CTP
timeFrame: 52 weeks
measure: the changes of lipid parameters (LDL-C,mmol/L；HDL-C,mmol/L；TG,mmol/L；TC,mmol/L；Apo A，mmol/L；Apo B，mmol/L )
timeFrame: 13, 26, 39, 52 week
measure: myopathic events, hepatic function, renal function and other adverse events.
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The second affiliated hospital of Zhejiang University
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: Min Lou, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: