Clinical trial NCT04149483: Statin Treatment for UnruptureD Intracranial anEurysms Study
Official title: Application of Atorvastatin in the Treatment of Patients With Intracranial Unruptured Aneurysms
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Intracranial Aneurysm
Inflammation Vascular
Keywords: High resolution magnetic resonance
Atorvastatin
Ruptured risk
Lead sponsor: Beijing Neurosurgical Institute
Sponsor class: OTHER
First posted: 2019-11-04
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was designed to identify whether there is a measurable reduction in inflammation in walls of intracranial aneurysms with oral atorvastatin.

Detailed description: Unruptured intracranial aneurysms (UIAs) are increasingly detected and often remain clinically asymptomatic for a long time before rupture. However, once the UIAs ruptured, the incidence of mortality rate varies from 30% to 60% within 6 months. Thus, the risk of UIAs rupture should be weighed, and need an individual criterion for predicting rupture in clinical decision making.

Histopathological studies indicated that inflammation may play an important role in the formation, growth, and rupture of UIAs. Wall enhancement of a saccular aneurysm on high resolution magnetic resonance (HRMRI) is a proven sign of inflammatory change and might predict an unsteady state of an intracranial saccular aneurysm.

Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase and are established first-line treatments for hypercholesterolemia. Statins produce a range of pleiotropic effects in addition to inhibition of cholesterol synthesis, especially to reduce inflammation, which may be important in reducing the growth and rupture of UIAs.

In the study, participants known to have UIA that is not planned for treatment and has not yet ruptured, take atorvastatin daily for six months, and have an HRMRI scan before and after to look for the role of atorvastatin in inflammation.

Eligibility criteria: Inclusion Criteria:

1. Be aged 18 or over, male or non-pregnant female;
2. patients have a saccular UIA identified on imaging (CT, MRI or DSA), and the aneurysm ≥3mm;
3. patients with wall enhancement of aneurysm by MRI VWI before treatment;
4. patients who is able to understand the objective of the trial, agrees and signs the written informed consent form.

Exclusion Criteria:

1. Patient with MRI contraindications: metallic implant, contrast allergy, claustrophobia, etc.;
2. Planned treatment of the aneurysm within 6 months;
3. Patient taking the drugs, which might have an anti-inflammatory effect, such as aspirin, statin, immunosuppressive drug, etc.
4. Dyslipidemia or severely impaired liver or renal functions
5. Retreatment of recurrent aneurysm;
6. Pregnant or lactating women;
7. Patients with malignant diseases, such as liver disease, kidney disease, congestive heart failure, malignant tumors, etc;
8. Poor compliance patients.

Primary outcomes:
measure: The change in aneurysm wall inflammation as measured by MRI vessel wall imaging (VWI).
timeFrame: 6 months
Secondary outcomes:
measure: Change of aneurysmal morphology between pre-treatment and the 6 months follow-up periods.
timeFrame: 6 months
measure: Changes of CRP in UIA patients between pre-treatment and the 6 months follow-up periods.
timeFrame: 6 months
measure: Changes of TNF-α in UIA patients between pre-treatment and the 6 months follow-up periods.
timeFrame: 6 months
measure: Changes of IL-1β in UIA patients between pre-treatment and the 6 months follow-up periods.
timeFrame: 6 months
measure: Changes of IL-6 in UIA patients between pre-treatment and the 6 months follow-up periods.
timeFrame: 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Neurosurgical Institute and Beijing Tiantan Hospital
state: Beijing
Study officials:
References:
citation: Li W, Zhang Y, Tian Z, Zhu W, Liu J, Zhang Y, Yang X, Tian DC. Statin treatment for unruptured intracranial aneurysms study: a study protocol for a double-blind, placebo-controlled trial. Stroke Vasc Neurol. 2020 Dec;5(4):410-415. doi: 10.1136/svn-2020-000353. Epub 2020 May 6.