Limiting AAA With Metformin (LIMIT) Trial

NCT ID: NCT04500756

Last Updated: 2025-04-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 314 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-28
• Study Completion Date: 2028-06-30

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?

Conditions

Abdominal Aortic Aneurysm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Metformin group

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.

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

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?

Placebo Group

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

One group will be randomized to receive the study drug Metformin and the other group will receive a placebo

Interventions

Metformin

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?

Intervention Type: DRUG

Placebo

One group will be randomized to receive the study drug Metformin and the other group will receive a placebo

Intervention Type: OTHER

Other Intervention Names

AAA

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 50 to 95 years inclusive;

4. Have a maximal orthogonal infrarenal aortic diameter between 35 and < 50 mm for males and between 30 and < 45 mm for females as measured by CTA;

5. Eligible participants must have an estimated glomerular filtration rate (eGFR) of ≥ 30 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 if possible) 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 hour before contrast, 50 mg PO prednisone + 50 mg PO diphenhydramine These individuals will also be given the option of CT scan without contrast if unwilling to follow the premedication as indicated above; 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 > 3.5 cm; 14. Uncontrolled hypertension defined as Systolic BP≥200, or considered to have hypertensive emergency or urgency.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kaiser Permanente

OTHER

Sponsor Role: collaborator

VA Palo Alto Health Care System

FED

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Ronald L. Dalman, MD

Division Chief of Stanford Vascular Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ronald Dalman, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford Hospital and Clinics

Stanford, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sohrab Sami

Role: CONTACT

ssami@stanford.edu

412-452-7137

Ronald Dalman, MD

Role: CONTACT

rld@stanford.edu

650-725-5227

Facility Contacts

Lori McDonnell

Role: primary

lorimcd2@stanford.edu

650-498-5521

Ronald Dalman, MD

Role: backup

rld@stanford.edu

650-725-5227

Other Identifiers

1R61HL146835-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

4R33HL146835-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-56500

Identifier Type: -

Identifier Source: org_study_id