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NCT Number: NCT06405971

Metformin in Patients With Unruptured Vertebrobasilar Dissecting Aneurysms (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.

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Key information

Conditions

Dissecting Aneurysm of Cerebral Artery Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100010, China

Location status: Recruiting

Location contact

Ming Lv, MD,PhD

CONTACT

[email protected]

13701376177

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

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.

Primary outcomes

  1. 3-dimensional wall enhancement volume rate (3D-WEVR)

    Time frame: 6 months after taking the drug

    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 (%).

Secondary outcomes

  1. Morphological changes in VBDAs

    Time frame: 6 months after taking the drug

    change in the maximum diameter of the aneurysm by ≥1 mm or the presence of a daughter aneurysm was defined as a morphologic change

  2. Characteristic changes in the internal lumen of VBDAs

    Time frame: 6 months after taking the drug

    change of intramural hematoma by ≥1 mm or disappearance of false lumen defined as characteristic changes in the internal lumen

  3. Changes in C-reactive protein

    Time frame: 6 months after taking the drug

    The unit of C-reactive protein is mg/dL.

  4. changes in serum inflammatory markers

    Time frame: 6 months after taking the drug

    e.g., IL-1β, IL-2R, IL-6, IL-8, IL-10, TNF-α. The unit of serum inflammatory markers is pg/ml.

  5. changes in serum inflammatory markers

    Time frame: 6 months after taking the drug

    e.g., MMP-3, MMP-9. The unit of serum inflammatory markers is ng/ml.

  6. 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

    Time frame: 6 months after taking the drug

    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)

  7. Wall enhancement index (WEI)

    Time frame: 6 months after taking the drug

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Linggen Dong, MD

CONTACT

[email protected]

18844738529

Ming Lv, Ph D.

CONTACT

[email protected]

13701376177

Sponsors and collaborators

Lead sponsor

Ming Lv

Other

Registry information

Official study title

Metformin in Patients With Unruptured Vertebrobasilar Dissecting Aneurysms: a Prospective, Randomized Study (METTLE)

Acronym: METTLE

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
May 9, 2024
Registry last updated
Feb 6, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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