Metformin for Abdominal Aortic Aneurysm Growth Inhibition (MAAAGI)

Metformin for AAA Growth Inhibition, a Randomized Controlled Trial

A multi-centre population-based open-label randomized controlled trial with allocation concealment and blinded outcome assessment will examine if up to 2g metformin daily slows AAA growth in patients with small AAAs who do not have diabetes.

Study Overview

• Status: Enrolling by invitation
• Conditions: Abdominal Aortic Aneurysm
• Intervention / Treatment: Drug: Metformin; Other: Standard care

Detailed Description

Subjects with no history of diabetes will be recruited from a cohort of patients with diagnosed AAA and a maximum aortic diameter of 30-49mm for men and 30-44mm for women.

A total of 500 subjects with AAA will be included in the study, 250 in each study arm. Patients will be randomised to metformin or standard care in a 1:1 ratio.

CT imaging and AAA US will be performed at baseline, 24 months and end of study, as well as if necessary according to clinical routine. Study drug will start at baseline and continue through completion.

When all enrolled subjects have completed the 24-month follow-up (including imaging) an interim analysis will be performed to assess for efficacy and safety; if there is no trend towards a positive effect or signs of a harmful effect of metformin, the study will be stopped at this phase.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Sverige
    • Uppsala, Sverige, Sweden
      • Uppsala University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of written informed consent.
2. Male and female patients.
3. Age 50-80 years.
4. Documented AAA Ø 30-49 mm for men and 30-44 mm for women.
5. Fasting p-glucose <7.0 mmol/L. Fasting is defined as no caloric intake for ≥8 h.

Exclusion Criteria:

1. Short expected survival.
2. History of current or previous diabetes mellitus.
3. Current or previous use of metformin.
4. Not expected to tolerate metformin.
5. Contraindications to metformin treatment according to SmPC
6. Known or suspected connective tissue disorder (Marfans syndrome, etc), infected or inflammatory aneurysm, aneurysm development after aortic dissection or previous surgery of the infrarenal aorta.
7. Enrollment in either another investigational drug or medical device study or another investigational study of an approved drug or medical device within 30 days prior to enrollment of the current study.
8. If, in the opinion of the investigator, it is not in the patient's medical interest to participate in the study or the patient is unlikely to be able to comply with the study protocol.
9. Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin target dose of 2g daily; Metformin tablets taken orally with target dose of 2g daily plus standard care	Drug: Metformin; Metformin target dose 2 g daily
Active Comparator: Standard care; Standard care includes help with smoking cessation if applicable; encouragement of physical activity and a healthy diet; blood pressure control; statin and anti-platelet therapy treatment if the patient have clinical manifestations of atherosclerotic disease.	Other: Standard care; Abdominal aortic aneurysm surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abdominal aortic aneurysm (AAA) diameter growth rate	To examine if up to 2g metformin administered daily over a five-year period slows AAA growth measured as computed tomography (CT) imaging assessed AAA diameter (mm) in patients with small AAAs who do not have diabetes.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abdominal aortic aneurysm (AAA) volume growth rate	To examine if up to 2g metformin administered daily over a five-year period slows AAA growth measured as computed tomography (CT) imaging assessed AAA volume (ml) in patients with small AAAs who do not have diabetes.	5 years

Collaborators and Investigators

• Sponsor: Uppsala University Hospital
• Investigators: Principal Investigator: Jon Unosson, PhD, Uppsala University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2020
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: January 1, 2020
• First Submitted That Met QC Criteria: January 7, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: MAAAGI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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