Metformin for the treatment of unruptured vertebrobasilar dissecting aneurysm (METTLE): study protocol for a double-blinded randomised controlled trial.

BACKGROUND: Vertebrobasilar dissecting aneurysm (VBDA) has high morbidity and mortality rates, and it is an important cause of stroke in young and middle-aged adults. Previous studies have shown that aneurysm wall inflammation is a major factor contributing to the high risk of aneurysm growth and rupture. Metformin inhibits inflammation and may be a suitable candidate drug for VBDA. Here, we report the protocol for a study designed to evaluate the ability of metformin to reduce the degree of aneurysm wall inflammation in patients with VBDA, as measured by high-resolution vessel wall imaging (HR-VWI). METHODS: The study is a multicentre, prospective, randomised, controlled, and blinded clinical trial. Sixty patients with unruptured VBDA who meet the inclusion/exclusion criteria will be recruited competitively from three hospitals in China. Patient recruitment began in May 2024 and is expected to end in December 2025. The patients will be randomised (1:1) to treatment or placebo (n = 30 in each group), receiving either 250-mg metformin or placebo orally twice per day for 6 months. The primary outcome will be the change in VBDA wall inflammation measured by HR-VWI. The secondary outcomes will be changes in VBDA morphology, typical imaging signs, and inflammatory biomarkers. DISCUSSION: Previous studies on metformin for the treatment of intracranial aneurysms have been performed in animals. However, prospective clinical studies in humans are lacking. Therefore, this study will provide insights into the anti-inflammatory effects of metformin in inhibiting VBDA growth and rupture and may reveal a new treatment modality for unruptured VBDA. The protocol has been approved by the Ethics Committee of Beijing Tiantan Hospital (approval no. KY2023-188-02). All patients will be required to provide written informed consent prior to participation. The results of the study will be disseminated through peer-reviewed journals and at relevant academic conferences. TRIAL REGISTRATION: NCT06405971. Registered on May 9, 2024.