Metformin in Patients with Unruptured Vertebrobasilar Dissecting Aneurysms: a Prospective, Randomized Study (METTLE)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- 3-dimensional wall enhancement volume rate (3D-WEVR)
研究概览
简要总结
Vertebrobasilar dissecting aneurysms (VBDAs) are one of the most important causes of stroke in young and middle-aged people, and the natural history of VBDAs is complex and varied, often leading to high rates of disability and mortality. For some patients with VBDAs who are not suitable for surgical entrapment and intervention, pharmacologic therapy may be used to slow the progression of VBDAs. Metformin (MET) has been shown to act as an anti-inflammatory, anti-oxidative stress and improve vascular endothelial function by inhibiting smooth muscle cell phenotypic transformation, proliferation, migration and apoptosis, thereby reducing the incidence of intracranial aneurysms and rupture rates, and MET may be a suitable candidate. Inflammatory response plays an important role in the occurrence, development and rupture of VBDAs. Inflammatory response in the aneurysm wall can cause endothelial and smooth muscle cell injury and apoptosis, leading to degenerative changes in the vessel wall and increasing the risk of rupture of VBDAs. High-resolution magnetic resonance vessel wall imaging (HR-VWI), which can clearly show the structure of the vessel wall and reflect the active degree of inflammatory reaction in the aneurysm wall, has been widely used in the assessment of intracranial aneurysm instability. In this study, we propose to conduct a multicenter, prospective, randomized study to investigate whether MET reduces the degree of aneurysm wall inflammatory response in VBDAs by performing HR-VWI scans in patients with VBDAs and obtaining quantitative parameters reflecting the inflammatory response of the aneurysm wall.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
To ensure the reliability of the research results, a study committee consisting of 5 members will be formed. The committee comprised a 2-member data safety monitoring committee and a 3-member clinical event review committee. These committee members were blinded to the treatment group assignments. Any disagreements were resolved by a third member of the clinical events adjudication committee. All five committee members reviewed and resolved any discrepancies through consensus.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years and ≤75 years, gender is not limited;
- •Patients with previously untreated, unruptured stable VBDAs clearly diagnosed by DSA, CTA or MRA;
- •Patients with aneurysm wall enhancement as shown by HR-VWI of 3.0T high field strength MRI whole body scanner at Tsinghua University;
- •Baseline mRS score ≤2;
- •Patients voluntarily participated in this study and signed an informed consent form.
排除标准
- •Patients with aneurysms located in non-vertebral basilar artery sites (mainly referring to bifurcation saccular aneurysms);
- •Patients with combined diabetes or its complications;
- •Patients who are allergic to any components in MET;
- •Pregnant and lactating female patients;
- •Patients with other immune diseases in combination, patients taking immunosuppressants or anti-inflammatory drugs (such as long-term use of aspirin, statin, hormones and other drugs);
- •Target aneurysm-related symptoms were severe at the time of diagnosis, and the mRS score was ≥3;
- •VBDAs have received interventional or surgical treatment;
- •Those with severe allergy to the contrast agent gadolinium terlumate glucosamine (Gd-DTPA) (skin rash not counted);
- •Those with severe renal disease resulting in renal insufficiency (glomerular filtration rate <30ml/(min·1.73m2));
- •Patients with metal implants in the body (e.g., cardiac stents, cardiac prosthetic valves, pacemakers, metal joints, steel plates, non-removable metal dentures, etc.);
- •Patients known to suffer from dementia or psychiatric disorders and claustrophobia who are unable to complete the magnetic resonance examination;
- •Patients with other serious diseases combined at the time of diagnosis and with an expected survival time of less than 1 year;
- •Patients who are participating in clinical trials of other drugs or devices.
- •Other conditions judged by the investigator to exist that are unsuitable for enrollment.
研究组 & 干预措施
Drug Group
Patients in the drug group were given one oral tablet of metformin hydrochloride enteric capsule each day after breakfast and dinner at a dose of 250 mg per tablet.
干预措施: Metformin (Drug)
Placebo group
Patients in the placebo group were given one oral tablet of placebo (capsule filled with corn starch) each day after breakfast and dinner at a dose of 250 mg per tablet.
干预措施: Metformin (Drug)
结局指标
主要结局
3-dimensional wall enhancement volume rate (3D-WEVR)
时间窗: 6 months after taking the drug
Changes in the degree of wall enhancement of VBDAs at the time of patient enrollment and after 6 months of oral drug administration were measured by HR-VWI, i.e., the quantitative wall enhancement parameters 3D-WEVR was compared between the drug group and the placebo group at the end of the 6-month treatment period. The unit of 3D-WEVR is percentage (%).
次要结局
- Proportion of patients with VBDAs who developed cerebral infarction, transient ischemic attack, cerebral hemorrhage, and symptoms of compression in the drug and placebo groups were recorded(6 months after taking the drug)
- Morphological changes in VBDAs(6 months after taking the drug)
- changes in serum inflammatory markers(6 months after taking the drug)
- Wall enhancement index (WEI)(6 months after taking the drug)
- Characteristic changes in the internal lumen of VBDAs(6 months after taking the drug)
- Changes in C-reactive protein(6 months after taking the drug)
研究者
Ming Lv
Principal Investigator
Beijing Tiantan Hospital