Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Drug Group | Experimental | 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. |
|
| Placebo group | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | Patients 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 (%). | 6 months after taking the drug |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 6 months after taking the drug |
| Characteristic changes in the internal lumen of VBDAs |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Linggen Dong, MD | Contact | 18844738529 | donglinggen@163.com | |
| Ming Lv, Ph D. | Contact | 13701376177 | dragontiger@163.com |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Tiantan Hospital | Recruiting | Beijing | Beijing Municipality | 100010 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11259724 | Result | Schievink WI. Spontaneous dissection of the carotid and vertebral arteries. N Engl J Med. 2001 Mar 22;344(12):898-906. doi: 10.1056/NEJM200103223441206. No abstract available. | |
| 25987283 | Result | Debette S, Compter A, Labeyrie MA, Uyttenboogaart M, Metso TM, Majersik JJ, Goeggel-Simonetti B, Engelter ST, Pezzini A, Bijlenga P, Southerland AM, Naggara O, Bejot Y, Cole JW, Ducros A, Giacalone G, Schilling S, Reiner P, Sarikaya H, Welleweerd JC, Kappelle LJ, de Borst GJ, Bonati LH, Jung S, Thijs V, Martin JJ, Brandt T, Grond-Ginsbach C, Kloss M, Mizutani T, Minematsu K, Meschia JF, Pereira VM, Bersano A, Touze E, Lyrer PA, Leys D, Chabriat H, Markus HS, Worrall BB, Chabrier S, Baumgartner R, Stapf C, Tatlisumak T, Arnold M, Bousser MG. Epidemiology, pathophysiology, diagnosis, and management of intracranial artery dissection. Lancet Neurol. 2015 Jun;14(6):640-54. doi: 10.1016/S1474-4422(15)00009-5. |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
Not provided
Not provided
Simple randomized controlled trial
Not provided
Not provided
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.
change of intramural hematoma by ≥1 mm or disappearance of false lumen defined as characteristic changes in the internal lumen
| 6 months after taking the drug |
| Changes in C-reactive protein | The unit of C-reactive protein is mg/dL. | 6 months after taking the drug |
| 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. | 6 months after taking the drug |
| changes in serum inflammatory markers | e.g., MMP-3, MMP-9. The unit of serum inflammatory markers is ng/ml. | 6 months after taking the drug |
| 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 | To record patients with VBDAs who developed cerebral infarction, transient ischemic attack, cerebral hemorrhage, and pressure symptoms in the drug and placebo groups, and to clarify whether MET suppresses ischemic events, hemorrhagic events, and pressure-occupying events (defined as ischemic events, hemorrhagic events, and pressure-occupying events if the patient's mRS scores are increased and associated with a target aneurysm) | 6 months after taking the drug |
| Wall enhancement index (WEI) | 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 WEI was compared between the drug group and the placebo group at the end of the 6-month treatment period. Quantitative parameter WEI has no units. | 6 months after taking the drug |
| 24824740 | Result | Sikkema T, Uyttenboogaart M, Eshghi O, De Keyser J, Brouns R, van Dijk JM, Luijckx GJ. Intracranial artery dissection. Eur J Neurol. 2014 Jun;21(6):820-6. doi: 10.1111/ene.12384. Epub 2014 Feb 22. |
| 31035900 | Result | Quan K, Song J, Yang Z, Wang D, An Q, Huang L, Liu P, Li P, Tian Y, Zhou L, Zhu W. Validation of Wall Enhancement as a New Imaging Biomarker of Unruptured Cerebral Aneurysm. Stroke. 2019 Jun;50(6):1570-1573. doi: 10.1161/STROKEAHA.118.024195. Epub 2019 Apr 30. |
| 30026386 | Result | Larsen N, von der Brelie C, Trick D, Riedel CH, Lindner T, Madjidyar J, Jansen O, Synowitz M, Fluh C. Vessel Wall Enhancement in Unruptured Intracranial Aneurysms: An Indicator for Higher Risk of Rupture? High-Resolution MR Imaging and Correlated Histologic Findings. AJNR Am J Neuroradiol. 2018 Sep;39(9):1617-1621. doi: 10.3174/ajnr.A5731. Epub 2018 Jul 19. |
| 31960286 | Result | Lv N, Karmonik C, Chen S, Wang X, Fang Y, Huang Q, Liu J. Wall Enhancement, Hemodynamics, and Morphology in Unruptured Intracranial Aneurysms with High Rupture Risk. Transl Stroke Res. 2020 Oct;11(5):882-889. doi: 10.1007/s12975-020-00782-4. Epub 2020 Jan 20. |
| 27808265 | Result | Etminan N, Rinkel GJ. Unruptured intracranial aneurysms: development, rupture and preventive management. Nat Rev Neurol. 2016 Dec;12(12):699-713. doi: 10.1038/nrneurol.2016.150. Epub 2016 Nov 3. |
| 30355091 | Result | Shimonaga K, Matsushige T, Ishii D, Sakamoto S, Hosogai M, Kawasumi T, Kaneko M, Ono C, Kurisu K. Clinicopathological Insights From Vessel Wall Imaging of Unruptured Intracranial Aneurysms. Stroke. 2018 Oct;49(10):2516-2519. doi: 10.1161/STROKEAHA.118.021819. |
| 33601368 | Result | He J, Li N, Fan Y, Zhao X, Liu C, Hu X. Metformin Inhibits Abdominal Aortic Aneurysm Formation through the Activation of the AMPK/mTOR Signaling Pathway. J Vasc Res. 2021;58(3):148-158. doi: 10.1159/000513465. Epub 2021 Feb 18. |
| 27088241 | Result | Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, Chu Y, Iyoha E, Segal JB, Bolen S. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Ann Intern Med. 2016 Jun 7;164(11):740-51. doi: 10.7326/M15-2650. Epub 2016 Apr 19. |
| 28776086 | Result | Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017 Sep;60(9):1577-1585. doi: 10.1007/s00125-017-4342-z. Epub 2017 Aug 3. |
| 27418629 | Result | Cameron AR, Morrison VL, Levin D, Mohan M, Forteath C, Beall C, McNeilly AD, Balfour DJ, Savinko T, Wong AK, Viollet B, Sakamoto K, Fagerholm SC, Foretz M, Lang CC, Rena G. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status. Circ Res. 2016 Aug 19;119(5):652-65. doi: 10.1161/CIRCRESAHA.116.308445. Epub 2016 Jul 14. |
| 32546267 | Result | Li S, Shi Y, Liu P, Song Y, Liu Y, Ying L, Quan K, Yu G, Fan Z, Zhu W. Metformin inhibits intracranial aneurysm formation and progression by regulating vascular smooth muscle cell phenotype switching via the AMPK/ACC pathway. J Neuroinflammation. 2020 Jun 16;17(1):191. doi: 10.1186/s12974-020-01868-4. |
| 41351119 | Derived | Dong L, Xu Z, Li Y, Wei D, Lin J, Wang C, Chen H, Lv M. Metformin for the treatment of unruptured vertebrobasilar dissecting aneurysm (METTLE): study protocol for a double-blinded randomised controlled trial. Trials. 2025 Dec 6;27(1):27. doi: 10.1186/s13063-025-09348-x. |