Dissecting Aneurysm of Cerebral ArteryMETTLENCT06405971
Metformin in Patients With Unruptured Vertebrobasilar Dissecting Aneurysms (METTLE)
A study testing Metformin in people with Dissecting Aneurysm of Cerebral Artery, run by Ming Lv at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Dissecting Aneurysm of Cerebral Artery
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2024to 1 Jun 2025
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing Tiantan Hospital
Beijing, Beijing Municipality, 100010
Ming Lv, MD,PhD, 13701376177, dragontiger@163.com
About this study
Official title: Metformin in Patients With Unruptured Vertebrobasilar Dissecting Aneurysms: a Prospective, Randomized Study (METTLE)
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.
- Conditions
- Dissecting Aneurysm of Cerebral Artery
- Being tested
- Metformin
- Keywords
- Vertebrobasilar dissecting aneurysms, Metformin, High-resolution vessel wall imaging, Inflammatory reaction
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Metformin |
| 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. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 (%).
Measured: 6 months after taking the drug
Secondary outcomes (7)
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
Measured: 6 months after taking the drug
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
Measured: 6 months after taking the drug
Changes in C-reactive protein
The unit of C-reactive protein is mg/dL.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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.
Measured: 6 months after taking the drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2024
- Study start1 Jun 2024
- Primary completion1 Jan 2025
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Dissecting Aneurysm of Cerebral ArteryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Simple randomized controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ming Lv
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ming Lv, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06405971
- Sponsor's protocol ID
- Ming Lv
- Acronym
- METTLE
- Status last verified
- Aug 2024
- First submitted
- 28 Apr 2024
- Last updated
- 6 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 11259724Debette 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.
PubMed 25987283Sikkema 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.
PubMed 24824740Quan 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.
PubMed 31035900Larsen 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.
PubMed 30026386Lv 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.
PubMed 31960286Etminan 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.
PubMed 27808265Shimonaga 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.
PubMed 30355091He 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.
PubMed 33601368Maruthur 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.
PubMed 27088241Rena 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.
PubMed 28776086Cameron 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.
PubMed 27418629Li 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.
PubMed 32546267Dong 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.
PubMed 41351119