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

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

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

Study Overview

• Status: Recruiting
• Conditions: Dissecting Aneurysm of Cerebral Artery; Inflammation Vascular; Intramural Hematomas
• Intervention / Treatment: Drug: Atorvastatin 20mg

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 Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mirzat Turhon, MD; Phone Number: +8618699158800; Email: 18699158800@163.com

Study Locations

• China
  • Beijing, China
    • Not yet recruiting
    • Mirzat Turhon
    • Contact: Mirzat Turhon, MD; Phone Number: +86-010-59978852; Email: 18699158800@163.com
  • Beijing
    • Beijing, Beijing, China, 100070
      • Recruiting
      • Beijing Neurosurgical Institute and Beijing Tiantan Hospital
      • Contact: Mirzat Turhon, MD; Phone Number: +86-18699158800; Email: 18699158800@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: SCREENING
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1.Change of aneurysm wall inflammation as measured by HR-VW-MRI.	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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of aneurysmal morphology parameter （the largest diamater）	Change of aneurysmal morphology parameter between pre-treatment and the 6 months follow-up periods.	6 months
Change of wall features of UVBDAs	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)	6 months
Change of inflammatory markers in UVBDAs patients	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)	6 months

Collaborators and Investigators

• Sponsor: Beijing Neurosurgical Institute

Publications and helpful links

General Publications

• Turhon M, Kang H, Huang J, Li M, Liu J, Zhang Y, Wang K, Yang X, Zhang Y. Atorvastatin for unruptured intracranial vertebrobasilar dissecting aneurysm (ATREAT-VBD): protocol for a randomised, double-blind, blank-controlled trial. BMJ Open. 2022 Apr 28;12(4):e059616. doi: 10.1136/bmjopen-2021-059616.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2021
• Primary Completion (ACTUAL): January 1, 2022
• Study Completion (ANTICIPATED): July 30, 2022

Study Registration Dates

• First Submitted: May 31, 2021
• First Submitted That Met QC Criteria: June 21, 2021
• First Posted (ACTUAL): June 29, 2021

Study Record Updates

• Last Update Posted (ACTUAL): April 6, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Atorvastatin; High resolution magnetic resonance
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Hemorrhage; Inflammation; Aneurysm; Aneurysm, Dissecting; Hematoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: BNI-20210601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data are available on reasonable request.
• IPD Sharing Time Frame: starting 6 months after publication
• IPD Sharing Access Criteria: Data are available on reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No