Vertebrobasilar Dolichoectasia Treatment With Sirolimus

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Longitudinal changes of CAWE on 5T HR-VWI in VBD following 3 and 6 months of sirolimus treatment. [Time frame: 3 and 6 months]
• Longitudinal changes of SAWE on 5T HR-VWI VBD following 3 and 6 months of sirolimus treatment. [Time frame: 3 and 6 months]
• Longitudinal changes of FAWE in VBD on 5T HR-VWI 3 and 6 months of sirolimus treatment. [Time frame: 3 and 6 months]
• Longitudinal changes of WEVR on 5T HR-VWI in VBD following 3 and 6 months of sirolimus treatment. [Time frame: 3 and 6 months]

Secondary outcome measures (12)

• Longitudinal changes of CAWE on 5T HR-VWI in VBD following 12 months of sirolimus treatment. [Time frame: 12 months]
• Longitudinal changes of SAWE on 5T HR-VWI VBD following 12 months of sirolimus treatment. [Time frame: 12 months]
• Longitudinal changes of FAWE on 5T HR-VWI VBD 12 months of sirolimus treatment. [Time frame: 12 months]
• Longitudinal changes of WEVR on 5T HR-VWI in VBD following 12 months of sirolimus treatment. [Time frame: 12 months]
• Longitudinal changes of vascular dilation on 5T MRA in VBD following 3, 6, and 12 months of sirolimus treatment. [Time frame: 3, 6, and 12 months]
• Longitudinal changes of vascular tortuosity on 5T MRA in VBD following 3, 6, and 12 months of sirolimus treatment. [Time frame: 3, 6, and 12 months]
• Longitudinal changes of vascular elongation on 5T MRA in VBD following 3, 6, and 12 months of sirolimus treatment. [Time frame: 3, 6, and 12 months]
• Longitudinal changes of thrombus volume in VBD following 3, 6, and 12 months of sirolimus treatment. [Time frame: 3, 6, and 12 months]
• Longitudinal changes in plasma SGK1 levels following 1, 3, 6, and 12 months of sirolimus treatment in VBD patients. [Time frame: 1, 3, 6, and 12 months]
• Incidence of ischemic stroke in VBD patients at 3, 6, and 12 months. [Time frame: 3, 6, and 12 months]
• Incidence of subarachnoid hemorrhage associated with VBD rupture in VBD patients at 3, 6, and 12 months. [Time frame: 3, 6, and 12 months]
• modified Rankin Scale in VBD patients at 3, 6, and 12 months. [Time frame: 3, 6, and 12 months]

Eligibility criteria

Inclusion criteria

• Age≥18 years, any gender;
• Patients with VBD confirmed by DSA/CTA/MRA;
• No history of VBD rupture and no surgical treatment for VBD;
• mRS<4;
• Positive plasma SGK1;
• History of posterior circulation infarction or accompanied by VBD-related symptoms/signs;
• 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;
• Capable of signing an informed consent form with the accompaniment and understanding of a guardian.

Exclusion criteria

• History of malignant tumors;
• Pregnancy or lactation;
• Sirolimus allergy;
• Hydrocephalus requiring urgent surgical intervention or respiratory failure requiring life support treatment;
• 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);
• History of immunosuppressive therapy;
• Acute cerebral infarction within the last month or definite high signal on DWI indicating acute or subacute cerebral infarction;
• Acute stage of intracranial hemorrhage as indicated by CT;
• History of VBD rupture or surgery;
• Presence of acute active infection (such as severe bacterial, viral or fungal infection);
• Uncontrolled diabetes (HbA1c≥7%);
• History of liver or lung transplantation;
• Presence of organic heart disease;
• History of arteriovenous thrombosis;
• Patients taking only antiplatelet drugs or only statin drugs;
• 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.);
• Currently participating in other clinical studies;
• Presence of contraindications for MRI examination;
• Other situations not suitable for inclusion.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Huashan Hospital, Fudan University — Shanghai

Identifiers

NCT: NCT07634120 · KY2026-724

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗