Vertebrobasilar Dolichoectasia Treatment With Sirolimus

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• Vertebrobasilar Insufficiency 20

Vertebrobasilar Insufficiency

20 studies on the registry are indexed under Vertebrobasilar Insufficiency; 8 are open to participants now.

This study's planned enrollment of 12 is below the median of 90 across 14 interventional studies indexed under Vertebrobasilar Insufficiency.

Lead sponsor

Huashan Hospital is the lead sponsor of 239 studies on the registry; 102 are open to participants now.

Study arms

• Experimental
  sirolimus group

  Participants will receive oral sirolimus 2mg/d continuously for 6 months.

  Drug: Sirolimus

• No intervention
  control group

Interventions

• DrugSirolimus

  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.

Primary outcomes

1. 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.

   Time frame: 3 and 6 months

2. 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.

   Time frame: 3 and 6 months

3. 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.

   Time frame: 3 and 6 months

4. 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.

   Time frame: 3 and 6 months

Secondary outcomes

1. 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.

   Time frame: 12 months

2. 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.

   Time frame: 12 months

3. 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.

   Time frame: 12 months

4. 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.

   Time frame: 12 months

5. 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.

   Time frame: 3, 6, and 12 months

6. 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.

   Time frame: 3, 6, and 12 months

7. 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.

   Time frame: 3, 6, and 12 months

8. 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.

   Time frame: 3, 6, and 12 months

9. 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.

   Time frame: 1, 3, 6, and 12 months

10. 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.

    Time frame: 3, 6, and 12 months

11. 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.

    Time frame: 3, 6, and 12 months

12. 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.

    Time frame: 3, 6, and 12 months

13. 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.

    Time frame: 3, 6, and 12 months

14. 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.

    Time frame: 1, 3, 6, and 12 months

15. 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.

    Time frame: 1, 3, 6, and 12 months