Atorvastatin in the TREATment of Intracranial Unruptured VertebroBasilar Dissecting Aneurysms

Not Applicable

• Conditions: Dissecting Aneurysm of Cerebral Artery; Inflammation Vascular; Intramural Hematomas
• Interventions: Drug: Atorvastatin 20mg

• Registration Number: NCT04943783
• Lead Sponsor: Beijing Neurosurgical Institute

Brief Summary

This study was designed to whether there is a measurable reduction in inflammation in walls of unruptured vertebrobasilar dissecting aneurysms with atorvastatin.

Detailed Description

Unruptured vertebrobasilar dissecting aneurysms (UVBDAs) are a pathological condition of the vertebrobasilar artery caused by hypertension, atherosclerosis, and infection. Hematoma between intima and media can progressively occlude the parent artery. Thus lead to decreasing perfusion of the distal perforator vessels and even cause cerebral infarction. Even worse, ruptured VBDAs can lead to subarachnoid hemorrhage and eventually death of the patients. Thus, risk of UVBDAs rupture should be weighed, and need an individual criterion for predicting rupture in clinical decision making.

Recently, many histopathological studies indicated that inflammation may play an important role in the formation, growth, and rupture of aneurysms. High-resolution vessel wall MRI (HR-VW-MRI) has been increasingly applied in clinical practice and is the only noninvasive method for imaging the structure of the vascular wall.

Wall enhancement of an aneurysm on high resolution magnetic resonance (HRMRI) is a proven sign of inflammatory change and might predict an unsteady state of an intracranial aneurysm. Besides, a previous study has demonstrated that HR-MRI can provide valuable information, such as parameters of intramural hematomas, double lumens and intimal flaps, in the diagnosis and follow-up UVBDAs.

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used cholesterol-lowering drugs and are established as first-line treatments for hypercholesterolemia. In addition, statins exert pleiotropic effects to protect the vasculature. Statins can reduce the inflammation of the vessel wall and mobilize endothelial progenitor cells for aneurysmal endothelial cell repair. Statins can also inhibit the expression of several matrix metalloproteinases by smooth muscle cells and macrophages, which may be important in reducing the growth and rupture of UVBDAs.

In this study, participants with UVBDAs that are not planned for surgical treatment and has not yet ruptured, take atorvastatin daily for six months, and have a HRMRI scan before and after conservative therapy to look for the role of atorvastatin in inflammation.

Study Timeline

• Study First Submitted: 2021-05-31
• Status Verified: 2021-06
• Study First Submitted QC: 2021-06-21
• Study First Posted: 2021-06-29
• Study Start: 2021-07-01
• Primary Completion: 2022-01-01
• Last Update Submitted: 2022-03-28
• Last Update Posted: 2022-04-06
• Study Completion: 2022-07-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Be aged 18 or over, male or non-pregnant female;
2. Patients have a unruptured vertebrobasilar dissecting aneurysm identified on imaging (CT, MRI or DSA)
3. Patients with wall enhancement and intramural hematomas of UVBDAs by HR-VW-MRI before treatment.
4. Patients who is able to understand the objective of the trail, agrees and signs the written informed consent form.

Exclusion Criteria

1. The aneurysm types of non-dissecting aneurysm, such as saccular aneurysms, fusiform aneurysms and traumatic aneurysms, etc.;
2. Patients with MRI contraindications: metallic implant, contrast allergy, claustrophobia, etc.;
3. Planned treatment of the aneurysm within 6 months;
4. Several 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 diseases, congestive heart failure, malignant tumors, etc.;
8. Poor compliance patients;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Atorvastatin	Atorvastatin 20mg	Atorvastatin, 20mg once a day, for six months

Primary Outcome Measures

Name	Time	Method
1.Change of aneurysm wall inflammation as measured by HR-VW-MRI.	6 months	Change of aneurysm wall enhancement index of at least 20% on HR-VM-MRI at the end of 6 months of atorvastatin 20mg daily treatment, compared to no treatment.

Secondary Outcome Measures

Name	Time	Method
Change of aneurysmal morphology parameter （the largest diamater）	6 months	Change of aneurysmal morphology parameter between pre-treatment and the 6 months follow-up periods.
Change of wall features of UVBDAs	6 months	Change of wall features of UVBDAs, which is intramural hematoma between pre-treatment and the 6 months follow-up periods. (The maximum diameter of the false lumen was compared)
Change of inflammatory markers in UVBDAs patients	6 months	Change of inflammatory markers in UVBDAs patients between pre-treatment and the 6 months follow-up periods. (CRP, TNF alpha, IL-2,6,8,10 and IL-1 beta)

Trial Locations

Locations (2)

Mirzat Turhon; 🇨🇳 Beijing, China

Beijing Neurosurgical Institute and Beijing Tiantan Hospital; 🇨🇳 Beijing, Beijing, China