Limiting AAA With Metformin (LIMIT) Trial

• Status: Not yet recruiting
• Trial end date: 2028-12-01
• Target enrollment: 0
• Participant gender: All

Summary

In this research, the investigators are looking at the effects of a drug called metformin may have on the growth of abdominal aortic aneurysm (AAA)s. AAA is an abnormal enlargement of the aorta, which is the large artery in the abdomen (stomach area). The enlargement of the aorta carries a risk that it will rupture and cause life-threatening bleeding in the abdomen (belly). In this study the investigators hope to learn how metformin is associated with the enlargement or change in size of the AAA in study participants. Smaller studies have suggested that metformin may reduce the rate at which aortic aneurysms enlarge. This study will test this question: does metformin prevent AAAs from growing larger?

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Stanford University
• Collaborators: Kaiser Permanente; National Heart, Lung, and Blood Institute (NHLBI); VA Palo Alto Health Care System
• Treatments: Metformin

Criteria

Inclusion Criteria:

1. Provision of signed and dated informed consent;

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Male or female, aged 55 to 90 years inclusive;

4. Have a maximal orthogonal infrarenal aortic diameter between 35 and 49 mm inclusive as measured by CTA;

5. Eligible participants must have an estimated glomerular filtration rate (eGFR) of ≥ 45 ml/min/1.73 m2 at the initiation of trial participation, and must remain ≥ 30 ml/min/1.73 m2 throughout the term of the study to continue participation;

6. HgbA1c must be ≤ 6.5% at initiation to receive study medication;

7. Ability to take oral medication and be willing to adhere to the medication regimen throughout the course of the trial;

8. Must be willing and able to undergo two computed tomographic aortograms (CTA, with timed intravenous iodinated contrast injections) at initiation and termination of study participation;

9. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening, with an agreement to use such a method of contraception during study participation and for an additional 4 weeks after the end of study drug administration.

Exclusion Criteria:

1. Diagnosis of, or taking medications for, diabetes mellitus, as defined as a fasting blood glucose ≥ 140 mg/dl, and/or non-fasting blood glucose ≥ 200 mg/dl, or HgbA1c ≥ 6.5% at baseline evaluation;

2. Known hypersensitivity to metformin hydrochloride or iodinated radiographic contrast medium;

3. Presence of metabolic acidosis, defined as total CO2 below the lower limit of normal on chemistry panel obtained during determination of study eligibility;

4. Expected survival less than two years;

5. Prior surgical AAA repair, or anticipated repair within two years;

6. Known thoracic aortic aneurysm disease, as defined as a prior dissection or thoracic aortic diameter > 5 cm);

7. The presence of known syndromic aortic conditions, including but not limited to Ehlers Danlos or Marfan Syndromes, or the at-risk allele in the ACTA2 gene mutation or similar conditions;

8. Severe liver disease, jaundice, or active hepatitis;

9. Severe anemia, defined as a Hgb < 10g/dl;

10. Concurrent participation in other investigational drug trials;

11. For female participants of childbearing potential: pregnancy, intent to become pregnant, lactation, or unwilling or unable to use an effective method of contraception;

12. Alcoholism or chronic excessive alcohol intake.