Metformin in Patients with Unruptured Vertebrobasilar Dissecting Aneurysms (METTLE) (METTLE)

February 4, 2025 updated by: Ming Lv

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100010
        • Recruiting
        • Beijing Tiantan Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Drug Group
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
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.
Placebo Comparator: Placebo group
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 (%).
6 months after taking the drug

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
6 months after taking the drug
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
6 months after taking the drug
Changes in C-reactive protein
Time Frame: 6 months after taking the drug
The unit of C-reactive protein is mg/dL.
6 months after taking the drug
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.
6 months after taking the drug
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 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
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)
6 months after taking the drug
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.
6 months after taking the drug

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ming Lv

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2024

Primary Completion (Actual)

January 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

April 28, 2024

First Submitted That Met QC Criteria

May 6, 2024

First Posted (Actual)

May 9, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 4, 2025

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Ming Lv

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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