About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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;
Trial design
Parallel
Treatments tested in this trial
Metformin
DrugPatients in the drug group took one tablet of metformin hydrochloride enteric capsule orally each day after breakfast and dinner, and the dose of each tablet was 250mg.
Treatment groups
Trial outcomes
Primary outcomes
3-dimensional wall enhancement volume rate (3D-WEVR)
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 (%).
Secondary outcomes
Morphological changes in VBDAs
change in the maximum diameter of the aneurysm by ≥1 mm or the presence of a daughter aneurysm was defined as a morphologic change
Characteristic changes in the internal lumen of VBDAs
change of intramural hematoma by ≥1 mm or disappearance of false lumen defined as characteristic changes in the internal lumen
Changes in C-reactive protein
The unit of C-reactive protein is mg/dL.
changes in serum inflammatory markers
e.g., IL-1β, IL-2R, IL-6, IL-8, IL-10, TNF-α. The unit of serum inflammatory markers is pg/ml.
Sponsors and contacts
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Ming Lv
Lead sponsor
Beijing Tiantan Hospital
Sponsor institution