Limiting AAA With Metformin (LIMIT) Trial

Brief Title

Limiting AAA With Metformin (LIMIT) Trial

Official Title

LIMItIng AAA With meTformin (LIMIT) Trial

Brief 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?
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

The primary outcome measure will be the change in maximal orthogonal diameter of the infrarenal aorta, as measured by computed tomographic (CT) aortography, in centimeters.

Secondary Outcome

 Profile of Adverse cardiovascular events

Condition

Abdominal Aortic Aneurysm

Intervention

Metformin

Study Arms / Comparison Groups

 Metformin group

Description:  Participants will either be assigned to take metformin 500 mg tablet(s) daily or identical tablet(s) that contain no active drug, also taken every day. Over the first four weeks of the study, you will increase your dosage every week by one pill, so at the end of the first month you will be taking up to four pills per day. If you develop any symptoms or side effects from pill ingestion during this process, your dose will be decreased to the last number of pills you were able to take without developing side effects.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

480

Start Date

February 28, 2022

Completion Date

December 2028

Primary Completion Date

December 2026

Eligibility 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 for males
             and between 35 and 45 mm for females 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 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.

         13. Common iliac artery aneurysms > 2.75 cm;

         14. Uncontrolled hypertension defined as Systolic BP≥200, or considered to have
             hypertensive emergency or urgency.
      

Gender

All

Ages

55 Years - 90 Years

Accepts Healthy Volunteers

No

Contacts

Ronald Dalman, MD, 6507246211, [email protected]

Location Countries

United States

Location Countries

United States

NCT ID

NCT04500756

Organization ID

IRB-56500

Secondary IDs

1R61HL146835-01A1

Responsible Party

Principal Investigator

Study Sponsor

Stanford University

Collaborators

 Kaiser Permanente

Study Sponsor

Ronald Dalman, MD, Principal Investigator, Stanford University

Verification Date

March 2022