Clinical trial NCT06405971: Metformin in Patients with Unruptured Vertebrobasilar Dissecting Aneurysms (METTLE)
Official title: Metformin in Patients with Unruptured Vertebrobasilar Dissecting Aneurysms: a Prospective, Randomized Study (METTLE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Dissecting Aneurysm of Cerebral Artery
Keywords: Vertebrobasilar dissecting aneurysms
Metformin
High-resolution vessel wall imaging
Inflammatory reaction
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2024-05-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Simple randomized controlled trial
Primary purpose: TREATMENT

Brief summary: 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: Inclusion Criteria:

1. Age ≥18 years and ≤75 years, gender is not limited;
2. Patients with previously untreated, unruptured stable VBDAs clearly diagnosed by DSA, CTA or MRA;
3. Patients with aneurysm wall enhancement as shown by HR-VWI of 3.0T high field strength MRI whole body scanner at Tsinghua University;
4. Baseline mRS score ≤2;
5. Patients voluntarily participated in this study and signed an informed consent form.

Exclusion Criteria:

1. Patients with aneurysms located in non-vertebral basilar artery sites (mainly referring to bifurcation saccular aneurysms);
2. Patients with combined diabetes or its complications;
3. Patients who are allergic to any components in MET;
4. Pregnant and lactating female patients;
5. 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);
6. Target aneurysm-related symptoms were severe at the time of diagnosis, and the mRS score was ≥3;
7. VBDAs have received interventional or surgical treatment;
8. Those with severe allergy to the contrast agent gadolinium terlumate glucosamine (Gd-DTPA) (skin rash not counted);
9. Those with severe renal disease resulting in renal insufficiency (glomerular filtration rate \<30ml/(min·1.73m2));
10. Patients with metal implants in the body (e.g., cardiac stents, cardiac prosthetic valves, pacemakers, metal joints, steel plates, non-removable metal dentures, etc.);
11. Patients known to suffer from dementia or psychiatric disorders and claustrophobia who are unable to complete the magnetic resonance examination;
12. Patients with other serious diseases combined at the time of diagnosis and with an expected survival time of less than 1 year;
13. Patients who are participating in clinical trials of other drugs or devices.
14. Other conditions judged by the investigator to exist that are unsuitable for enrollment.

Primary outcomes:
measure: 3-dimensional wall enhancement volume rate (3D-WEVR)
timeFrame: 6 months after taking the drug
Secondary outcomes:
measure: Morphological changes in VBDAs
timeFrame: 6 months after taking the drug
measure: Characteristic changes in the internal lumen of VBDAs
timeFrame: 6 months after taking the drug
measure: Changes in C-reactive protein
timeFrame: 6 months after taking the drug
measure: changes in serum inflammatory markers
timeFrame: 6 months after taking the drug
measure: changes in serum inflammatory markers
timeFrame: 6 months after taking the drug
measure: 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
timeFrame: 6 months after taking the drug
measure: Wall enhancement index (WEI)
timeFrame: 6 months after taking the drug
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
state: Beijing
Study officials:
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