ATREAT-VBD: Atorvastatin in the TREATment of Intracranial Unruptured VertebroBasilar Dissecting Aneurysms

Sponsor

Beijing Neurosurgical Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04943783

Collaborator

(none)

Enrollment

Locations

Arms

12.9

Anticipated Duration (Months)

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Dissecting Aneurysm of Cerebral Artery Intramural Hematomas Inflammation Vascular	Drug: Atorvastatin 20mg	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Screening

Official Title:

Application of Atorvastatin in the TREATment of Patients With Intracranial Unruptured Vertebrobasilar Dissecting Aneurysms

Actual Study Start Date :

Jul 1, 2021

Actual Primary Completion Date :

Jan 1, 2022

Anticipated Study Completion Date :

Jul 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atorvastatin Atorvastatin, 20mg once a day, for six months	Drug: Atorvastatin 20mg One with the intervention (Atorvastatin, 20mg OD), 20 patients for this arm.
No Intervention: No drug no drug

Arm

Intervention/Treatment

Experimental: Atorvastatin

Atorvastatin, 20mg once a day, for six months

Drug: Atorvastatin 20mg

One with the intervention (Atorvastatin, 20mg OD), 20 patients for this arm.

No Intervention: No drug

no drug

Outcome Measures

Primary Outcome Measures

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

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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

The aneurysm types of non-dissecting aneurysm, such as saccular aneurysms, fusiform aneurysms and traumatic aneurysms, etc.;
Patients with MRI contraindications: metallic implant, contrast allergy, claustrophobia, etc.;
Planned treatment of the aneurysm within 6 months;
Several impaired liver or renal functions;
Retreatment of recurrent aneurysm;
Pregnant or lactating women;
Patients with malignant diseases, such as liver disease, kidney diseases, congestive heart failure, malignant tumors, etc.;
Poor compliance patients;