Metformin in Patients with Unruptured Vertebrobasilar Dissecting Aneurysms (METTLE)

NCT06405971 | Recruiting DMC

• 1 other identifier: Ming Lv
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Dissecting Aneurysm of Cerebral Artery

Keywords

Vertebrobasilar dissecting aneurysms; Metformin; High-resolution vessel wall imaging; Inflammatory reaction

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• Morphological changes in VBDAs

  6 months after taking the drug

• Characteristic changes in the internal lumen of VBDAs

  6 months after taking the drug

• Changes in C-reactive protein

  6 months after taking the drug

• changes in serum inflammatory markers

  6 months after taking the drug

• changes in serum inflammatory markers

  6 months after taking the drug

Study Arms (2)

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.

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.

Drug: Metformin

Interventions

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.

Drug Group; Placebo group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Ming Lv: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100010, China

RECRUITING

Related Publications (14)

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• 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.

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  PMID: 30026386 BACKGROUND

• 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.

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  PMID: 30355091 BACKGROUND

• 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.

  PMID: 33601368 BACKGROUND

• 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.

  PMID: 27088241 BACKGROUND

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  PMID: 28776086 BACKGROUND

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  PMID: 27418629 BACKGROUND

• 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.

  PMID: 32546267 BACKGROUND

• 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.

  PMID: 41351119 DERIVED

MeSH Terms

Conditions

Inflammation

Interventions

Metformin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Central Study Contacts

Linggen Dong, MD

CONTACT

18844738529; donglinggen@163.com

Ming Lv, Ph D.

CONTACT

13701376177; dragontiger@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Simple randomized controlled trial

Study Record Dates

• First Submitted: April 28, 2024
• First Posted: May 9, 2024
• Study Start: June 1, 2024
• Primary Completion: January 1, 2025
• Study Completion: June 1, 2025
• Last Updated: February 6, 2025

Record last verified: 2024-08

Locations

CN (1)