Vertebrobasilar Dolichoectasia Treatment With Sirolimus

Vertebrobasilar Dolichoectasia Treatment With Sirolimus: a Pilot Trial Based On 5.0 T MRI

The aim of this pilot trial is to assess the efficacy of sirolimus in reducing wall enhancement in vertebrobasilar dolichoectasia(VBD) on 5 T high-resolution magnetic resonance vessel wall imaging(HR-VWI) via anti-inflammatory mechanisms, clarify the efficacy of sirolimus in delaying the progression of VBD, evaluate the safety of sirolimus in the treatment of VBD.

Study Overview

• Status: Not yet recruiting
• Conditions: Vertebrobasilar Dolichoectasia
• Intervention / Treatment: Drug: Sirolimus

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liuxun Hu; Phone Number: +8615868058299; Email: 19111220090@fudan.edu.cn
• Study Contact Backup: Name: Wei Zhu; Phone Number: +8615868058299; Email: drzhuwei@fudan.edu.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200040
      • Huashan Hospital, Fudan University
      • Contact: Wei Zhu; Phone Number: +8615868058299; Email: 19111220090@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age≥18 years, any gender;
2. Patients with VBD confirmed by DSA/CTA/MRA;
3. No history of VBD rupture and no surgical treatment for VBD;
4. mRS<4;
5. Positive plasma SGK1;
6. History of posterior circulation infarction or accompanied by VBD-related symptoms/signs;
7. Currently and in the future, need to take antiplatelet and statin drugs simultaneously, or currently and in the future, do not need to take antiplatelet and statin drugs;
8. Capable of signing an informed consent form with the accompaniment and understanding of a guardian.

Exclusion Criteria:

1. History of malignant tumors;
2. Pregnancy or lactation;
3. Sirolimus allergy;
4. Hydrocephalus requiring urgent surgical intervention or respiratory failure requiring life support treatment;
5. Abnormal hepatic and/or renal function (serum transaminase > 40 U/L; serum creatinine > 110 μmol/L); and/or abnormal white blood cells/platelets (white blood cells count < 3.5 × 10⁹/L or > 9.5 × 10⁹/L; platelets count < 100 × 10⁹/L or > 300 × 10⁹/L);
6. History of immunosuppressive therapy;
7. Acute cerebral infarction within the last month or definite high signal on DWI indicating acute or subacute cerebral infarction;
8. Acute stage of intracranial hemorrhage as indicated by CT;
9. History of VBD rupture or surgery;
10. Presence of acute active infection (such as severe bacterial, viral or fungal infection);
11. Uncontrolled diabetes (HbA1c≥7%);
12. History of liver or lung transplantation;
13. Presence of organic heart disease;
14. History of arteriovenous thrombosis;
15. Patients taking only antiplatelet drugs or only statin drugs;
16. Patients taking or needing to take CYP3A4 inhibitors (ketoconazole, itraconazole, voriconazole, clarithromycin, erythromycin, telithromycin, ritonavir, atazanavir, diltiazem, verapamil, cyclosporine, amiodarone, sildenafil, grapefruit juice, etc.) or CYP3A4 inducers (rifampicin, rifabutin, phenobarbital, phenytoin, carbamazepine, dexamethasone, St. John's wort, etc.);
17. Currently participating in other clinical studies;
18. Presence of contraindications for MRI examination;
19. Other situations not suitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control group
Experimental: sirolimus group; Participants will receive oral sirolimus 2mg/d continuously for 6 months.	Drug: Sirolimus; Sirolimus is an mTORC1/ mTORC2 inhibitor that has received approval from the U.S. Food and Drug Administration (FDA) and has recently been successfully used to treat lymphatic malformations and venous/lymphatic malformations associated with the same PIK3CA GOF mutations. Participants of sirolimus group will receive oral sirolimus 2mg/d continuously for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal changes of CAWE on 5T HR-VWI in VBD following 3 and 6 months of sirolimus treatment.	Using 5T HR-VWI, we quantify longitudinal changes of vascular CAWE (3D circumferential arterial wall enhancement: mean signal intensity in T1+Gd images) at 3 and 6 months following initiation of sirolimus therapy. The primary objective of this study is to determine whether sirolimus exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD.	3 and 6 months
Longitudinal changes of SAWE on 5T HR-VWI VBD following 3 and 6 months of sirolimus treatment.	Using 5T HR-VWI, we quantify longitudinal changes of vascular SAWE (specific contrast uptake arterial wall enhancement: the difference in mean signal intensity between T1 and T1+Gd) at 3 and 6 months following initiation of sirolimus therapy. The primary objective of this study is to determine whether sirolimus exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD.	3 and 6 months
Longitudinal changes of FAWE in VBD on 5T HR-VWI 3 and 6 months of sirolimus treatment.	Using 5T HR-VWI, we quantify longitudinal changes of vascular FAWE (focal arterial wall enhancement: areas of the diseased artery with increased AWE) at 3 and 6 months following initiation of sirolimus therapy. The primary objective of this study is to determine whether sirolimus exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD.	3 and 6 months
Longitudinal changes of WEVR on 5T HR-VWI in VBD following 3 and 6 months of sirolimus treatment.	Using 5T HR-VWI, we quantify longitudinal changes of vascular WEVR (3D arterial wall enhancement volume rate) at 3 and 6 months following initiation of sirolimus therapy. The primary objective of this study is to determine whether sirolimus exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD.	3 and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal changes of CAWE on 5T HR-VWI in VBD following 12 months of sirolimus treatment.	Using 5T HR-VWI, we quantify longitudinal changes of vascular CAWE (3D circumferential arterial wall enhancement: mean signal intensity in T1+Gd images) at 12 months following initiation of sirolimus therapy. The primary objective of this study is to determine whether sirolimus exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD.	12 months
Longitudinal changes of SAWE on 5T HR-VWI VBD following 12 months of sirolimus treatment.	Using 5T HR-VWI, we quantify longitudinal changes of vascular SAWE (specific contrast uptake arterial wall enhancement: the difference in mean signal intensity between T1 and T1+Gd) at 12 months following initiation of sirolimus therapy. The primary objective of this study is to determine whether sirolimus exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD.	12 months
Longitudinal changes of FAWE on 5T HR-VWI VBD 12 months of sirolimus treatment.	Using 5T HR-VWI, we quantify longitudinal changes of vascular FAWE (focal arterial wall enhancement: areas of the diseased artery with increased AWE) at 12 months following initiation of sirolimus therapy. The primary objective of this study is to determine whether sirolimus exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD.	12 months
Longitudinal changes of WEVR on 5T HR-VWI in VBD following 12 months of sirolimus treatment.	Using 5T HR-VWI, we quantify longitudinal changes of vascular WEVR (3D arterial wall enhancement volume rate) at 12 months following initiation of sirolimus therapy. The primary objective of this study is to determine whether sirolimus exerts an anti-inflammatory effect on the diseased vertebrobasilar arterial wall in patients with VBD.	12 months
Longitudinal changes of vascular dilation on 5T MRA in VBD following 3, 6, and 12 months of sirolimus treatment.	Using 5T MRA, we quantify longitudinal changes of dilation(maximum diameter of the intracranial segment of the vertebral artery and basilar artery) of diseased vessel in VBD at 3, 6, and 12 months following sirolimus treatment.	3, 6, and 12 months
Longitudinal changes of vascular tortuosity on 5T MRA in VBD following 3, 6, and 12 months of sirolimus treatment.	Using 5T MRA, we quantify longitudinal changes of tortuosity(displacement distance of the intracranial segment of the vertebral artery and basilar artery) of diseased vessel in VBD at 3, 6, and 12 months following sirolimus treatment.	3, 6, and 12 months
Longitudinal changes of vascular elongation on 5T MRA in VBD following 3, 6, and 12 months of sirolimus treatment.	Using 5T MRA, we quantify longitudinal changes of elongation(length of the basilar artery) of diseased vessel in VBD at 3, 6, and 12 months following sirolimus treatment.	3, 6, and 12 months
Longitudinal changes of thrombus volume in VBD following 3, 6, and 12 months of sirolimus treatment.	Using 5T HR-VWI, we quantify longitudinal changes of thrombus volume in VBD at 3, 6, and 12 months following sirolimus treatment.	3, 6, and 12 months
Longitudinal changes in plasma SGK1 levels following 1, 3, 6, and 12 months of sirolimus treatment in VBD patients.	Longitudinal changes in plasma SGK1 levels (quantitative analysis of plasma SGK1 was performed via western blot) following 1, 3, 6, and 12 months of sirolimus treatment in VBD patients.	1, 3, 6, and 12 months
Incidence of ischemic stroke in VBD patients at 3, 6, and 12 months.	Incidence of ischemic stroke(newly developed infarct lesion confirmed by CT/MRI after onset of relevant symptoms/signs or newly developed infarct lesion confirmed by follow-up MRI at 3, 6, or 12 months) in VBD patients at 3, 6, and 12 months.	3, 6, and 12 months
Incidence of subarachnoid hemorrhage associated with VBD rupture in VBD patients at 3, 6, and 12 months.	Incidence of subarachnoid hemorrhage associated with VBD rupture(newly developed subarachnoid hemorrhage confirmed by CT/MRI after onset of relevant symptoms/signs or newly developed subarachnoid hemorrhage confirmed by follow-up MRI at 3, 6, or 12 months) at 3, 6, and 12 months.	3, 6, and 12 months
modified Rankin Scale in VBD patients at 3, 6, and 12 months.	modified Rankin Scale (mRS), a 7-level, clinician-reported, measure of global disability is measured in VBD patients at 3, 6, and 12 months.	3, 6, and 12 months
Five-level EuroQol five-dimensional questionnaire in VBD patients at 3, 6, and 12 months.	Five-level EuroQol five-dimensional questionnaire(EQ-5D-5L), a 5-level, measure of quality of life, is performed in VBD patients at 3, 6, and 12 months.	3, 6, and 12 months
The safety of sirolimus in VDB patients.	A serious adverse event (SAE) is any untoward medical occurrence that meets one or more of the following criteria, regardless of suspected causal relationship to the study intervention: (1) results in death; (2) is life-threatening; (3) requires inpatient hospitalization or prolongation of existing hospitalization; (4) results in persistent or significant disability or incapacity, or substantially disrupts normal life functions; or (5) constitutes an important medical event that, based on appropriate medical judgment, may jeopardize the patient's health or require medical or surgical intervention to prevent one or more of the outcomes listed in (1)-(4). SAEs will be actively monitored and systematically assessed at all scheduled follow-up visits (at 1, 3, 6, and 12 months post-baseline). In addition, participants are instructed to report any suspected SAE immediately to the study team via a dedicated 24/7 telephone hotline. To ensure timely detection and documentation.	1, 3, 6, and 12 months
The tolerability of sirolimus in VDB patients.	Based on prior clinical experience and sirolimus trial reports, adverse events (AEs) include oral ulcers, upper respiratory tract infections, headaches, respiratory diseases, stomatitis, seizures, and fever. Other commonly reported AEs also encompass nausea, vomiting, fatigue, dizziness, diarrhea, and mild allergic reactions such as rash or pruritus. In addition, mild infections, mild gastrointestinal disturbances, and fluctuations in blood pressure or heart rate have been observed. Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety, life-threatening event, or death caused by or associated with sirolimus, where the nature, severity, or incidence of such effect, event, or death was not previously identified in the investigational plan; or any other unanticipated serious problem related to sirolimus that concerns the rights, safety, or welfare of subjects.	1, 3, 6, and 12 months

Collaborators and Investigators

• Sponsor: Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 20, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Ischemia; Vertebrobasilar Insufficiency; Organic Chemicals; Macrolides; Lactones; Sirolimus
• Other Study ID Numbers: KY2026-724

Drug and device information, study documents

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